The management of skin
cancer in Australian general
practice
Christopher Bernard Del Mar
BSc (First Class Joint Honours)(Salford); BA (Cantab); MA (Cantab); MB BChir (Cantab);
Dip RCOG; FRACGP; FAFPHM.
Department of Social and Preventive Medicine at The University of Queensland
Thesis submitted for the degree of MD on 6 December 1999
Signed statement of sources:The work presented is, to the best of my knowledge, original and my own work except where
acknowledged in the text, and the material has not been submitted either in whole or in part
for a degree at this or any other university.
Acknowledgments
Thanks to Adèle Green, and Vic Siskind who read parts of early drafts of the thesis and
offered valuable advice. To the co-workers referenced within who worked on the different
studies. And to Vivienne and the children who have had to put up with a lot.
____________________________________
CB Del Mar
5 December 1999
—i—
Abstract
Background
This thesis looks at the management of skin cancer in general practice from a number of
viewpoints. In the literature review (Chapter 1) it is shown that there is surprisingly high
potential for both non-melanoma skin cancer (NMSC) and melanoma to contribute to the
workload of Australian general practitioners (GPs). This is because NMSC is so common.
More than 50% of Australians will be affected by NMSC during their lifetimes, which makes
it the most common cancer to affect Australians. It is more common than all other cancers
combined. Clearly this is likely to have an impact on the delivery of primary medical care.
Melanoma on the other hand has a considerably lower incidence ranking fifth among all
cancers in Australia (at 3400 in 1988) but only ninth equal among causes of death from cancer
per year (at 600 in 1988). It might have been thought therefore that it would have
considerably less impact on general practice, even in Australia where melanoma has the
highest worldwide incidence. However consideration of the diagnostic confusion with
melanomas that banal skin naevi represent means that naevi must be addressed. Two
important points emerge from the literature. Banal skin naevi are very common. The exact
numbers are difficult to estimate because of problems of definition and because they vary
with age. There are probably about 20 per adult (with greater numbers in adolescence). The
numbers vary considerably among individuals. The second point is that those with greater
numbers of naevi are at greatest risk of developing melanoma. This has important
implications for clinicians. It makes the difficulty of distinguishing melanomas from benign
naevi even more difficult: not only are there many naevi among which are few melanomas,
but those with the most naevi are more likely to have melanomas. Clearly this aspect of
melanoma management might impose considerable challenge and workload on GPs in
Australia. This leads to a literature search about the epidemiology of skin naevi, which is
described.
The issue of differentiating melanomas from naevi has attracted considerable attention from
previous researchers. Some have devised different strategies to assist clinicians and their
patients to do this. Two of the best known (the Glasgow ‘seven-point rule’ and the McGovern
‘ABCD rule’) emphasise the importance of change in a variety of factors relating to the
appearance of pigmented lesions. Change is so important a factor that if it is not present, the
likelihood of the lesion being malignant is very low.
— ii —
The potential of NMSCs to kill is relatively low. Most cause morbidity (mainly in the form of
minor surgery and care required for further follow-up and early detection of recurrences) out
of proportion to their lethal potential. This is unfortunately not true for melanoma. Melanoma
has a high lethal potential, particularly for lesions beyond a shallow depth of invasion. One
might predict therefore a high referral rate for melanomas compared to NMSC.
One of the important epidemiological facts well described in the literature is the age
distribution of both NMSC and melanoma. These are most common in the elderly (as the
incidence increases steadily with age) and men more than women. This has important
consequences for clinicians.
Estimating the workload on general practitioners
To explore these issues further, two national data sets of general practice activity in the area
were studied (Chapter II). The first was the Australian Morbidity and Therapeutics Study,
which examined the recorded clinical management of 495 GPs selected randomly from
around Australia (response rate 50.4%). Some of the reasons for encounter and diagnoses
were relevant to the area of interest. They included ‘malignant skin neoplasms’,
‘naevus/Mole’, and ‘other benign neoplasms’. Raw data of reports of these conditions were
drawn up. Using data about the proportion of all Medicare items used by the sample of GPs,
and the proportion of the total numbers of patients in Australia seen by the sample of GPs
during that recording period (two fortnights separated by about 6 months), it was possible to
calculate the actual incidence of these skin lesions managed by GPs in Australia. These
showed that malignant lesions were managed at a much higher rate for the middle aged and
elderly (for example in the >65 years, 86 and 106 encounters per 1,000 people annually). In
contrast naevi were most commonly managed in young females (with a maximum annual
incidence of 40/1,000 in women aged 15-24 years of age). The group having their benign
skin lesions managed were middle-aged women (45-64 years of age) with an annual incidence
of 23/1,000.
An important finding was that most skin cancers were managed in association with other
reasons for the consultation. Skin lesions were nearly twice as likely (60% compared to 36%
in which the problem was managed with others).
As expected, most lesions were managed by minor surgical means. Excisions were highest for
melanoma (40%), and then skin naevi (28%), and non-surgical means highest for other benign
lesions (26%). Referral to specialist services was highest for malignant lesions (22%) and
— iii —
lowest for other benign lesions (9%). It was not possible to determine from these data to what
extent there was ‘internal referral’, that is referral to another GP (perhaps in the same
practice) for excision. (This question was, however, examined in Chapter IV, see below).
There was a geographical distribution, some states (Queensland and the Northern Territory in
accordance with expectation, but also the Australian Capital Territory) having the highest
rates of managing malignant lesions and naevi of the skin.
Another data set was similarly studied, (Chapter II). This was the Australian Sentinel Practice
Research Network (ASPReN). One of the dozen conditions that 223 sentinel GPs from across
Australia recorded for two years was that of skin naevi. The raw data were transformed into
incidence rates by a similar method to that employed for the AMTS data, using estimated
resident populations provided by the Australian Bureau of Statistics, the total number of
consultations per week of each of the recorders, and the total number of consultations
recorded by Medicare for each state and time period. The total number of naevus
consultations for each state and month was estimated by the applying the observed rates per
GP consultation to the total number of consultations for all GPs. This allowed an estimate of
the rates to validate the data relating to skin naevi from the AMTS, but also to estimate the
changes of these consultations with time, including season. The results confirmed the striking
age differences with rates of consultation with respect to naevi by age and sex: the highest age
group being the 15-44 age group (at an annual rate of 22/1,000 people), and females (at 17
consultations per year /1,000) more than males (at 11/1,000).
The geographical distribution was less clearly linked to states of the highest sun incidence.
There was a striking variation in the consultation rate with season, with the hotter months
having consultation rates in the order of twice as common as the coldest (about 20
consultations per person per year compared with about 10 per person per year).
There are methodological differences in the two disparate methods that might account for the
differences in results between the two methods. Nevertheless there is sufficient agreement to
lend validity to the methods.
There are clinical consequences of the findings. In addition to the observation that skin
tumours form an important component of general practice, the observation that the clinical
activity appears to be dissonant to what is known about the distribution of malignancy
suggests that further exploration of the issue is warranted. In addition it is important to know
what ‘success’ all this clinical activity is having in harvesting cancers.
— iv —
Studying the patterns of excised melanocytic skin lesions
One way of investigating this was to examine the 1882 specimens removed from the skin over
an 11-week period and submitted for histology to one pathology service, Chapter III. Strict
definitions were applied to limit the lesions to principally those potentially concerned with
malignancy, and they were limited to melanocytic lesions of the skin.
The main finding was that few lesions were malignant. The overall ratio of malignant to total
lesions was only 3%. Excising a benign lesion confers no benefit to a patient because the
potential for any benign banal naevi to undergo malignant transformation is extremely small.
However there is a small subgroup of benign melanocytic lesions for which removal might
confer some direct or indirect benefit to patients. These include melanoma in situ and
Hutchinson’s melanotic freckle (which both have a high rate of malignant transformation to
melanoma), and dysplastic naevi (which carry such an important prognosis of high risk for
melanoma that patients with large numbers should perhaps be screened for melanomas
elsewhere on the body regularly). Including this group of ‘potentially malignant’ lesions
increased the rate of justified excisions to 8% of the total. Such low proportions raise several
questions. To what extent the total has been diluted by lesions excised for reasons other than
to exclude malignancy, such as cosmetic reasons and because of local discomfort. What the
causes of low ‘hit’ rates are, (and what an ideal should be). And whether GPs could be
assisted by some intervention to enable them to improve their diagnostic accuracy.
The data also confirmed that the majority (78%) of lesions removed from the skin in this
category was in the under 40 years of age. In contrast only a minority, (17%) of melanomas
submitted was from those under 40 years of age. Again the sex distribution favoured women
having lesions excised (60%), while in contrast they had only 37% of the melanomas
(invasive and in situ).
There are methodological problems from this type of analysis, (which are discussed at some
length). Nonetheless it is very likely that there is a dissonance between the care GPs are
offering patients in terms of skin naevi excisions and where their efforts might yield a greater
proportion of malignancies.
A more detailed, prospective study of excised melanocytic skin lesions
One way of addressing these questions was in a prospective study. Chapter IV outlines a
complex study with a descriptive and an intervention (experimental) arm. The descriptive
—v—
arm consisted of recruiting primary medical care doctors in a city in tropical Queensland and
obtaining information about all the melanocytic lesions that were removed surgically and
submitted to histology. This city acted as Control City in a quasi experiment in which another
city was provided with an intervention (see below). This allowed information to be obtained
about the reasons for the excisions, the extent to which there was ‘internal referral’ (between
the GPs of a practice). It also enabled some assessment of the pressure doctors felt themselves
to be under from patients to excise lesions that otherwise they did think had sufficient features
to warrant excision. This ‘patient pressure’ is something that was discussed anecdotally, but
was nowhere measured.
After pilot testing, the doctors and pathology services were recruited in the Control City. All
44 GPs, seven surgeons, and one dermatologist were recruited. Data were collected from the
previous six months and then prospectively for another two years. Every time a melanocytic
lesion was submitted to the pathology services in the Control City, a questionnaire was
generated and sent to the excising doctor. It asked about the specific areas of interest, (reason
for the excision, the level of pressure if any the doctor felt subject from the patient, and from
which if any other doctor the patient was referred). A total of 3,220 lesion were studied. The
demographics of the patients form whom they were removed confirmed the previous findings
above, that more females (58%) than males had lesions excised, and that the peak age group
was young (below the age of 30, with a median of only 28). The majority of lesions removed
were compound naevi (43%). Only 4% of lesions were melanomas, while 6% were
‘justifiably’ excised using the previous criteria in Chapter III, confirming the findings of the
previous study.
The majority of lesions (78%) were removed to exclude malignancy. Other reasons included
discomfort (10%) and cosmetic problems (5%). This confirms what had only been previously
assumed.
Most lesions were excised from the back (32%), followed by the face (13%). The ratio of
malignant to total excisions was highest for the lower leg/top of foot and the entire upper
limb, and lowest for the chest, abdomen and neck. This might have implications for clinical
practice: perhaps clinicians should have a higher index of suspicion for lesions on the lower
leg and the arm.
Data were available on the form of excision and the margins of normal tissue surrounding
each lesion. Conventional excision biopsy was employed for the great majority (82%), while
shave biopsy accounted for only 11%, and significantly less likely for lesions that were
potentially malignant (4%). Males had a greater geometric mean of margin excised around
— vi —
each lesion in comparison to females (3.1mm compared to 2.6mm). Older patients had greater
margins than younger (those older than 40 had mean margins of 3.5mm compared to less than
2.9mm for those 40 years and younger). Limiting the analysis to benign lesions demonstrated
the same effect, while there was no sex difference for malignant lesions. This may reflect the
greater concern the excising doctors had for good cosmetic results for female and younger
patients.
Patient pressure was found to be more influential as a perceived factor on the doctors than
expected. In only 22% of lesions did doctors feel themselves to be under no pressure from
their patient to excise the lesion. In as many as 13% did they feel that the reason to excise was
only because of patient pressure.
An intervention designed to improve the accuracy of excised melanocytic skin lesions
Earlier work in this thesis established that there is a case for improving the performance of
primary care doctors in the management of this very common diagnostic dilemma. It has also
been established that there are some specific areas that might contribute to the problem. These
include factors such as the role of benign naevi and the difficulty of distinguishing the rare
melanomas from among them. Also the phenomenon of patient pressure may be important.
Returning again to the importance eof change in the diagnostic process referred to in the
literature review, it follows that lesions that are not changing are unlikely to be melanomas.
Providing assistance with recording the appearance of doubtful lesions might improve the
diagnostic performance.
This idea was tested with an experiment in which two tropical Queensland cities were entered
into a randomised trial. Primary care doctors in the Intervention City were offered a simple
algorithm to act as a method of explaining the idea, and access to an instant-developing
camera designed to record doubtful naevi. The same outcomes were measured as in the
descriptive part of the study (see above). The results showed that in the six months before the
intervention was introduced, all the baselines measures were not statistically different
between Control and Intervention Cities. In the two years following the intervention, the
number of excised that was neither malignant nor potentially malignant fell significantly from
94% at baseline to 89% in the Intervention City but not the Control City. This change was
accompanied by an increase in the Intervention City from 2.5% to 5.7% of melanomas, while
in the Control City remained constant at 4.3 fro the baseline, although this difference did not
achieve significance. There was an increase in the Intervention City of the proportion of males
— vii —
and older patients from whom lesions were submitted for histology. This is line with
correcting the previously reported dissonance between excision patterns and optimal profiles
based on the epidemiology of melanomas. There was also a decrease in the proportion (from
78% to 72%) of lesions removed to exclude malignancy in the Intervention City compared to
the Control, although there was significant change in perceived patient pressure on the doctor
to excise.
Some process indicators of how the doctors used the cameras was obtained. They found the
photographs more useful for recording the shape of the lesions of doubtful naevi than their
colour.
The principal methodological shortcoming of the study lies in the fact that only a quasiexperiment could be mounted. It is therefore not implausible that some other influence was
responsible for the changes observed other than the intervention itself.
Nevertheless the findings are suggestive that doctors in high-incidence countries for
melanoma might find the employment of instant developing cameras useful for assisting the
diagnosis of doubtful naevi. They might reduce the excision rate for benign naevi without
compromising the detection rate of melanoma.
The potential of primary prevention
The potential for primary prevention in the role of reducing skin cancer is discussed in
Chapter V. Most primary prevention in Australia has concentrated on public messages for
avoiding sunlight. Some theoretical difficulties are raised against this, including the
possibility that some subgroups of people might be harmed by such a universal policy. This
comes from some case-control data suggesting that constant occupational sun exposure (that
is, in contrast to the intermittent exposure of recreational sun exposure) is protective against
melanoma.
During the Naevus Management Study from the Control City described above there was a
series of public health media campaigns in Queensland. Analysis of the data enabled an
estimate of the effect of the campaign on the excision rates of naevi. Despite the fact that the
principal objective of the awareness campaigns was to encourage young people to avoid
sunlight, there was an important effect on the excision rate. The effect of season has to be
adjusted for (possible because there was a season without an awareness campaign) to avoid a
confounding effect (the awareness campaigns were designed to coincide with the first hot
weather). More than 20% more lesions were excised during the campaign periods after
— viii —
adjustment for the confounding effects of season. There was not an increase in malignant or
potentially malignant lesions to match this. Unexpectedly there were fewer excisions in which
the doctor reported feeling under patient pressure to excise during the campaign times.
These data suggest that there might be unexpected effects of public campaigns on behaviour
that means that such campaigns might have a cost not previously estimated. There are other
possible costs such as anxiety that these extra but not worthwhile excisions signal.
There are other possible approaches to primary prevention against skin cancer argued for.
Perhaps GPs should have a greater role in the primary prevention against children who appear
to be particularly vulnerable to sunlight at an early age, and those identified as having
excessive numbers of skin naevi.
Conclusions
Skin cancer forms an important part of Australian general practice. Melanoma is the most
important area of skin cancer. GPs face considerable challenges to diagnosing between
melanomas and benign naevi. An intervention has been devised that appears to help them in
this. There may also be areas of primary prevention that GPs could make a new and useful
contribution.
— ix —
Table of contents:Chapter I
Skin cancer in Australia
A.
Types of skin cancer and their relationship to general practice ...............................................5
A. 1.
Secondary skin cancers .................................................................................................5
A. 2.
Primary skin cancers .....................................................................................................5
B.
Non-melanocytic skin cancer ...........................................................................................7
B. 1.
Estimates of the incidence of NMSC................................................................................7
B. 2. Impact of NMSC on Australians .........................................................................................8
B. 3. The potential to reduce the impact of NMSC on Australians..............................................9
1
Melanoma.................................................................................................................................9
C. 1. Incidence and importance ..................................................................................................9
C. 2
Is there an increasing incidence of melanoma with time?............................................11
C. 3.
Melanoma and general practice..................................................................................11
C. 4. Types of melanoma ....................................................................................................................12
C. 4. i Superficial spreading melanomas (SSM)...........................................................12
C. 4. ii Nodular melanomas ...........................................................................................12
C. 4. iii Lentigo maligna melanoma................................................................................13
C. 4. iv Acral-lentiginous melanoma ..............................................................................13
C. 4
Summary of the different histological types of melanoma ..................................13
D.
Aetiology of skin cancer ........................................................................................................15
D. 1. Sunlight and skin type .......................................................................................................15
D. 1. i Environmental comparisons....................................................................................................15
D. 1. ii Behavioural.............................................................................................................................15
D. 1. iii Constitutional factors.............................................................................................................16
D. 1. iv Childhood sunlight exposure .................................................................................................16
D. 1. v Deciding if the association between sunlight and sun cancer is causal ..................................16
D.2. Naevi .................................................................................................................................20
D. 2. i Benign naevi ............................................................................................................................20
D. 2. ii Atypical naevi.........................................................................................................................21
D. 2. iii Do naevi evolve into melanomas?.........................................................................................22
D. 2. iv Conclusions about naevi in general practice..........................................................................23
D.2 Other risk factors ..............................................................................................................23
E.
Diagnosis of melanoma..........................................................................................................23
E. 1. Differential diagnosis........................................................................................................23
E. 2. Multiple naevi ...................................................................................................................24
E. 3. Atypical naevi....................................................................................................................24
E. 4. Distinguishing SSMs from melanomas..............................................................................24
E. 5. Clinical performance in diagnosis ...................................................................................25
F.
Conclusions ............................................................................................................................29
Chapter II Skin cancer form the perspective of Australian general practice
A
Introduction to the issue ........................................................................................................31
The size of the Australian general practice workforce ........................................................................31
II B.
Australian Morbidity and Treatment Study (AMTS)........................................................32
II B. 1. Introduction to the AMTS method .............................................................................32
II.B 2.
Source of the data from the AMTS ......................................................................32
IIB 3.
Coding the AMTS data .............................................................................................32
IIB
4. Analyses of the AMTS data ........................................................................................34
IIB
5. Results of the AMTS ....................................................................................................34
b)
Associated conditions (AMTS data) .................................................................................39
c)
Management (AMTS data) ................................................................................................40
d)
Effects of state and territory (AMTS data) ........................................................................41
II.C
Australian Sentinel Practice Research Network (ASPReN) .....................................43
—1—
Introduction to the ASPReN method ...........................................................................................43
II.C 1. Source of the ASPReN data.........................................................................................44
II.C 2. ASPReN analyses undertaken .................................................................................45
II.C 3. ASPReN results ...........................................................................................................45
a) Effect of age and sex on consulting rate (ASPReN data) ................................................................45
b) Effect of State on consulting rate (ASPReN data)...........................................................................46
c) Secular changes of the ASPReN data ..............................................................................................48
II.D
Discussion ..............................................................................................................49
1. methodological problems ......................................................................................................49
a) Clustering of patients about GP recorders ..................................................................49
b)
Distribution of naevus consultations are recorded in relation to all
consultations......................................................................................................................49
c) Response bias..............................................................................................................49
Clinical significance of the findings.................................................................................................52
II.D
Chapter III
Accuracy of the diagnostic techniques used in clinical practice
Introduction to the problem..............................................................................................................55
Pathology company analysis of a series of pigmented naevi ...........................................................55
Method.........................................................................................................................................55
Results .........................................................................................................................................56
Discussion ...................................................................................................................................59
Methodological problems ....................................................................................................................59
Errors in failing to report lesions .........................................................................................................59
Errors in assigning lesions to correct assignments...............................................................................59
Bias introduced because the pathology service is not representative of pathology services in
Queensland...........................................................................................................................................59
Pigmented lesions other than melanocytic lesions had not been evaluated .........................................60
Other reasons than to exclude malignancy may have been responsible for the excision.....................60
Other methods of managing the lesions are not estimated – under-reporting bias ..............................60
Ability to generalise the findings.........................................................................................................61
External validation of the findings.......................................................................................................61
Clinical significance of the findings ....................................................................................................61
Chapter IV
D.1
D.2
D.3
D.4
D.5
D.6
D.7
D.8
Further studies into the management of naevi in primary care. The
naevus management study
A
Introduction to the methods ..............................................................................................65
B
The Naevus Management Study ........................................................................................65
C
Pilot testing .......................................................................................................................68
D
Method ..............................................................................................................................69
Choice of the cities.......................................................................................................................85
Recruitment of pathologists .........................................................................................................85
Recruitment of medical practitioners ...........................................................................................85
Difficulties ...................................................................................................................................85
melanocytic lesions ......................................................................................................................85
data management..........................................................................................................................85
The intervention ...........................................................................................................................85
Analyses
E
Results of the descriptive component of the study.............................................................88
Demographics variables.......................................................................................................................85
—2—
Histology..............................................................................................................................................85
Reasons for excision ............................................................................................................................85
Patient pressure ....................................................................................................................................85
Sites of excision ...................................................................................................................................85
Method of excision ..............................................................................................................................85
Margin of excision ...............................................................................................................................85
F
Results of the descriptive component of the study.............................................................88
Comparison at baseline........................................................................................................................105
Comparison after the intervention .......................................................................................................106
Process studies.....................................................................................................................................107
G
Discussion ..................................................................................................................115
G.1 Methodological problems ..........................................................................................................115
Generalisation to Australian practice .........................................................................116
Gold standard of diagnosis.........................................................................................116
Validity of questionnaire responses ...........................................................................116
Validity of the concept of patient pressure ................................................................116
Design of the experimental component of the study..................................................117
The effect of financial inducements to excise............................................................117
G.2 Clinical significance of the findings of the descriptive component .........................................118
Age and sex distribution of patients from whom melanocytic lesions were
excised........................................................................................................................118
G.3 Clinical significance of the findings of the intervention component .........................................120
Chapter V
Primary prevention — another approach?
Introduction...............................................................................................................................121
Interventions outside general practice ......................................................................................121
Problems with a primary skin cancer prevention approach ...............................................................121
There may be insufficient evidence ................................................................................121
The ethical need for increased stringency with regard to preventive measures ..............122
The anomaly with occupational exposure to sun and skin cancer rates. .........................122
Types of sun avoiding interventions..................................................................................................122
Estimating the harm from a primary care approach...........................................................................123
Rationale for the study ....................................................................................................123
Description of the study ..................................................................................................123
Results.............................................................................................................................124
Methodological problems................................................................................................129
Conclusions.....................................................................................................................129
Primary prevention as a part of general practice ............................................................................130
Role of general practice..................................................................................................................130
Nature of general practice in Australia ....................................................................................130
Introduction to primary prevention for skin cancer in general practice...................................131
Primary prevention within general practice: ............................................................................131
Skin cancer prevention: estimates of the possible benefits .......................................................132
Problems of primary prevention of skin cancer from general practice..............................................132
The message should be evidence-based. .........................................................................132
GPs are remiss in opportunistic preventive activities .....................................................133
It is not clear what the advice should be .........................................................................133
There may be pragmatic obstacles ..................................................................................133
Special advantages of primary prevention of skin cancer from general practice ..............................134
General reasons ...............................................................................................................134
—3—
Avoiding patients who might be harmed ........................................................................134
Selecting patients who will benefit especially ................................................................134
Conclusions ...............................................................................................................................135
Chapter VI
VI.A
VI.B
VI.C
VI.D
VI.E
Conclusions
Workload considerations..............................................................................................136
The dissonance between excision patterns and the epidemiology of melanoma .........136
Patient pressure to excise .............................................................................................137
Improve clinical management ......................................................................................129
Primary Prevention.......................................................................................................130
References ........................................................................................................................................132
—4—
Chapter I
Skin cancer in Australia
A.Types of skin cancer and their relationship to general practice
'Skin cancer' is a heterogeneous group of diseases. All cancers can be grouped into primary
and secondary.
A. 1.
Secondary skin cancers
These form a small minority of incident skin cancer, consisting of metastases that spread from
another primary site. These are uncommon, and usually represent a very serious prognostic
stage, dependent on the characteristics of the primary tumour.[1] Most general practitioners
(GPs) will encounter such problems rarely – usually never during a professional lifetime.
Their management usually requires specialist advice and techniques. Accordingly they will
not be addressed further in this thesis.
A. 2.
Primary skin cancers
There are two main groupings: melanoma; and non-melanocytic skin cancer (NMSC). These
will be addressed in considerably more detail below.
There are other forms of primary skin cancer. These are outlined in Table I. 1:-
—5—
Table I. 1.
Primary skin cancers that are neither melanomas or non-melanocytic skin cancers
(adapted from Chapter 8, Sarcoma and lymphoma by O'Rourke, MGE, and
Chapter 9, Appendegeal tumours by Gutteridge, BH, in Malignant skin tumours
(editors Emmett, AJJ and O'Rourke, MGE), Churchill Livingston 1982
London.[2])
Tumour type
description
Approximate incidence
Usually slow-growing and slow to
<< 1:1,000,000/year
Sarcomas of the skin
Dermato-fibro-sarcoma
metastasise
Kaposi sarcoma
Previously very rare, associated with a
<1:1,000,000/year (except
virus infection, and with acquired immune
in populations with
deficiency
AIDS)
Angiosarcoma of the skin
< 1:1,000,000/year
Atypical fibroxanthoma
Only described recently in Queensland
<1:1,000,000/year
Lymphoangio-sarcoma
Often associated with lymphoedema
< 1:1,000,000/year
following surgery, particularly after
radical breast axillary dissection
Lymphomas of the skin
Mycosis fungoides
This is often a manifestation of lymphoma
Approximately
deeper in the body, and consists of a T-
1:1,000,000/year
cell lymphoma infiltrating the skin
Primary cutaneous
It is often impossible to determine if the
lymphomas, (Hodgkins and
lymphoma arose on the skin initially or
non-Hodgkins)
metastased there.
Rare: < 1:1,000,000/year
Appendageal tumours
Apocrine and eccrine
A heterogeneous group of sweat-gland
Very rare
carcinomas
tumours
< 1:1,000,000/year
Sebaceous carcinomas
Rare, and usually affect the eyelids
< 1:1,000,000/year
Pilar carcinomas
(malignant hair follicle tumours)
Extremely rare
< 1:1,000,000/year
To estimate whether these incidence figures are important it is necessary to estimate how
likely a GP is to encounter each of these diseases. This requires the estimate of the population
for which each GP cares. This is undertaken in Chapter II, p29.
—6—
B.
Non-melanocytic skin cancer
There are two main groups of non-melanocytic skin cancer (NMSC): basal cell carcinoma
(BCC) and squamous cell carcinoma (SCC). They are well described, and have different
clinical characteristics.[1, 2]
Squamous cell carcinomas (SCCs) of the skin are more common in men than women, and
are associated with increasing age. The main aetiological factor is sunlight exposure. This will
be discussed in more detail in section D.1. of this Chapter, p15. Other aetiological factors
include other forms of ionising radiation, carcinogens such as benzene-containing petroleum
and arsenic, and chronic scarring ulcers, burns and infections. Microscopically the tumours
are characterised by excess keratin production arising from cells of the squamous epithelium
which are atypical in having enlarged and hyperchromic nucleii. While the cells are contained
external to the basement membrane the tumour is said to be in situ. If they are seen to be
breaching this they are designated invasive. SCCs exhibit variation in the degree of
differentiation of their squamous cells, with the most poorly differentiated (with anaplastic
rounded cells producing little keratinisation) associated with a less good prognosis.[3] The
main diagnostic difficulty is differentiating SCCs from solar keratoses and keratoacanthomas.
Basal cell carcinomas (BCCs) are formed of cells resembling those of the basal layers of the
epidermis. Most common on the head, neck and areas, they can occur on any part of the body.
They are very variable tumours, sometimes forming a simple nodule (the typical ‘nodular
BCC’) sometimes arising from a greater area of skin (typically a ‘multi-nodular BCC’), and
other scarring types. They typically have a pearly appearance to the edge, which may be
raised above the surrounding skin and tumour. Often the tumour undergoes necrosis so that it
ulcerates. The blood vessels contained within BCCs often dilate characteristically to form
telangectasia. They rarely metastasise. BCCs are common in sunny climates but also occur in
rare congenital diseases such as xeroderma pigmentosum in which there are defects in DNA
repair.[3] The main diagnostic difficulty is differentiating BCCs from trichoepitheliomas and,
when pigmented, from melanomas.
B. 1.
Estimates of the incidence of NMSC
British morbidity statistics report the annual rates of all 'malignant neoplasms of the skin' as
50/100,000.[4] This estimate was taken from recording general practice activity. Estimates of
NMSC in Australia have been undertaken by community based surveys. These have involved
experts examining people to reduce self-report bias. Estimates from these studies vary from
823/100,000/year in 1988[5] to 1,187/100,000/year.[6] Rates are higher in latitudes closer to
the equator (such as Queensland).[7]
—7—
These rates are somewhat difficult to compare because there is evidence of increasing
incidence with time.[8] [6]
Typically the ratio of BCC to SCC is 3:1. The ratio for males to females may approach 2:1 for
both forms.[6-8]
These Australian rates are extremely high. Two out of every three Australians will be afflicted
by NMSC during their life.[8]
B. 2. Impact of NMSC on Australians
The usual treatment recommended for both SCC and BCC is that of excision.[1, 9, 10] One
must assume that there is a considerable work load associated with the primary management
of these conditions. There are other methods of treating skin cancers other than by excision,
(including other destructive methods, expectant observation and referral, for example).
However it is difficult to find published information of the workload of NMSC in general
practice. The Australian Morbidity and Treatment Study reported the following crude rates of
different skin neoplasms:Table I. 2.
Reports of different skin neoplasms from the AMTS study (Adapted from
Bridges-Webb et al 1992)[11]
Problem
Percentage of all
Percentage of all new
problems (%)
problems (%)
0.7
0.9
Malignant skin neoplasm
Per 100 encounters
These data do not distinguish between NMSC and melanoma, (or any other form of skin
malignancy).
This aspect of skin cancer and workload is explored in more detail in Chapter II.
In contrast to melanoma, NMSC only account for 200 deaths/year in Australia.[12] The vast
majority of care is successful in terms of preserving life. This is compared with the success of
treating melanoma below in section C. 1.
—8—
1.0
B. 3. The potential to reduce the impact of NMSC on Australians
The massive incidence of NMSC implies that primary measures to reduce it should be
entertained. This is explored in detail in Chapter VI.
The small impact of NMSC on mortality is in the order of 200/17 000 000, or about one death
per 100 000 Australians annually. Using the equivalent calculations used above suggests that
more than 50 years of a full-time equivalent GP's life will be required on average to encounter
one such death. (Or, in other words, it will take more than 50 GPs to encounter a death from
NMSC in one year).
People who die from NMSC usually have another complicating problem contributing to the
illness, commonly a major internal malignancy or other debilitating illness which results in
immune deficiency.[1, 13] In addition there may be psychological factors associated with
some deaths from NMSCs. In 40% of deaths from BCC in Rhode Island, USA, the patient had
refused surgery.[14]
1
Melanoma
C. 1. Incidence and importance
The epidemiology of melanoma recently has been reviewed.[15] The incidence of melanoma
varies from as low as 0.2 per 100,000 in Japan to as high as 40 per 100,000 in
Queensland.[15] In Australia, although it ranks ninth as a cause of death from cancers, it has a
higher importance than this statistic would imply, Table I. 3.
—9—
Table I. 3. Most important cancers in Australia, (adapted after Armstrong 1988[15])
Type of cancer
New cases
Deaths
PYLL*
per year
per year
due to
Rank
Non-melanocytic skin cancer
Rank
cancer
Rank
95000
1
200
-
-
-
Colon + rectum
7000
2
3700
2
17800
2
Lung
5900
3
5300
1
27200
1
Breast
5100
4
2000
3
16300
3
Melanoma
3400
5
600
9=
7000
5
Prostate
3400
6
1400
4=
Bladder
2200
7
600
9=
Stomach
1800
8
1400
4=
5600
8
Non-Hodgkin’s lymphoma
1500
9
800
7
6200
7
Pancreas
1200
10
1200
6
5100
10
700
8
6900
6
Brain and nervous system
10300
4
Lymphocytic leukaemia
5400
9
(NMSC)
Non-lymphocytic leukaemia
*PYLL = person years of life lost before 70
As can be seen from Table I.3, melanoma ranks fifth most important in terms of its incidence.
Although it ranks lower in terms of actual numbers of deaths, it ranks higher (fifth) in the total
number of years of life lost before the age of 70. The latter is a more appropriate estimate of
importance because it takes into account the fact that melanoma kills people at a younger age
group than many other cancers which are more concentrated among the older members of the
population. (This pattern of incidence of melanoma with age is discussed in more detail
below).
(In contrast NMSC is by far the most common cancer — more in fact than all other cancers
added together. Its mortality is in contrast to this high incidence: very few NMSCs cause
death. Moreover NMSC kills mostly elderly people[14], so that the number of lives lost before
the age of 70 will be lower.)
Melanoma has importance for reasons of its effect on the quality of life as well as this simple
quantitative effect. Melanoma, when it kills by metastasis, often does so slowly because it
rarely compromises the immune or endocrine system. This means that until it exerts a pressure
effect on a vital area (such as the brain, or to a lesser extent on liver and lungs), melanoma
may mean many months or years of knowledge of metastases for the patient and family.[16]
— 10 —
This distress has not yet been quantified, but probably represents an important contribution to
the burden of suffering.
C. 2
Is there an increasing incidence of melanoma with time?
The incidence of melanoma is increasing at an accelerating pace. In Australia the incidence
has increased from 16/100,000 per year in the late 1960s to 32.7/100,000 in 1977, and was
over 40/100,000 in Queensland in 1986. This trend has been observed in every country in
which annual incidence figures have been collected.[17]
There is a controversy about whether this reported rise in the incidence is real or apparent
because:•
melanomas may be diagnosed at an earlier stage (a lead-time effect[18]) in
later years;
•
there may have been less adequate registration of melanomas in earlier
years;[19]
•
deaths from melanoma in many places have remained about constant over
this time period.[20, 21]
A small series of melanomas in NSW over a short time period does not support the
suggestion that the observed rise in incidence in Australia is an artifact—the observed increase
of melanomas appeared to be real.[22] Moreover, the death rate in at least one state (South
Australia) has been increasing also.[23] Therefore there must still be uncertainty over whether
the rise of melanoma is real or an artifact.
C. 3.
Melanoma and general practice
The best study on the effect of melanoma on general practice comes from New Zealand. Fifty
six GPs completed 2 614 brief records for each patient presenting a pigmented skin lesion for
assessment of malignancy over seven summer months. The peak age for consultations of
pigmented naevi occurred at 15-19 years for men and 30-44 for women. As many as 22% of
patients were biopsied by the GP as a means of initial management, and only 8% were
referred, (equally to dermatologists and surgeons).[24] There was a ratio of 65 consultations
for every clinical diagnosis of melanoma. This study emphasises the importance of the
management of naevi in the management of melanoma. No such information was available for
Australia at the time of starting this series of studies.
The incidence of melanoma is very high in Australia, almost certainly because of
environmental factors that are discussed below. It is an order higher than among those of the
— 11 —
countries in Europe to whom most Australians are closely related. Therefore the potential for
reducing the incidence of melanoma to that of the European countries from which much of the
Australian population is derived can be estimated:Percentage of
preventable melanomas
Incidence in Australia — lowest European incidence
=
Incidence in Australia
X 100
Using such methods, Armstrong has estimated that 96% of melanomas are potentially
preventable.[12] The potential for general practice to be involved in the prevention of
melanoma is explored further in Chapter VI.
C. 4. Types of melanoma
In their original paper, Clark et al [25] described three types of melanoma: Superficial
spreading melanoma (SSM); lentigo maligna melanoma; and nodular melanoma. Acral
lentiginous melanomas have been described subsequently.[26] Because some types of
melanoma may be more amenable to prevention, and may also pose different challenges to
management in general practice, they will be outlined briefly:
C. 4. i Superficial spreading melanomas (SSM)
SSMs account for the majority of melanomas, namely about 65%.[27, 28] An important
characteristic of superficial melanomas is that they are in the radial phase of growth. This
concept is important when it comes to detecting melanoma sufficiently early to confer survival
benefit. It was developed by Clark et al in a seminal paper.[25] The notion is that early
melanomas have a growth that is initially radial (in the same direction as the surface of the
skin), and may then develop a vertical phase (at right-angles to the surface). It is the latter that
is most dangerous in leading to deep spread into adjacent tissues and structures such as
lymphatics that allow the tumour to metastasise. Not all melanomas have a radial phase, (in
particular some nodular, and some acral-lentiginous), but in many even predominantly
nodular melanomas there is a superficial component from which it may be assumed that the
radial component growth arose.
SSMs are often flat and may resemble banal naevi on the skin. This is important, and will be
enlarged upon below (section I. E) in relation to diagnosis.
C.4. ii Nodular melanomas
Nodular melanomas, dominated by a vertical phase growth, are less common, (between 15-30
percent of all lesions treated in most series).[27, 28] The vertical phase growth results in a
raised nodule which often grows quickly. They have a more serious prognosis.[28]
— 12 —
C. 4. iii Lentigo maligna melanoma
Lentigo maligna melanomas account for between 4-10% of all cases. They arise on sunexposed surfaces, often from a precursor called a lentigo maligna, particularly on the face of
old people. This has been regarded as a vertical phase growth melanoma arising from an in
situ melanoma (the lentigo maligna).[29]
C. 4. iv Acral-lentiginous melanoma
Acral-lentiginous melanomas are characterised by being most commonly found on the soles of
the feet, palms of the hands, nail beds or mucous membranes. They are more common among
black races than whites, in whom it makes up only 2-8% of all melanomas. The subject was
reviewed from a series of 60 patients in Austria with this subgroup of melanomas.[26] The
important features of the findings from this study were that these melanomas were clinically
similar to superficial and nodular melanomas except for their site which made diagnosis more
difficult, that survival was also similar to superficial and nodular melanomas (with an
excellent five-year survival for those lesions whose Breslow thickness was less than
0.76mm[30]), but that the histological features had more in common with lentigo melanoma
than the former.
Black people have fewer melanomas.[17] Because they have relatively more acral lentiginous
melanomas, there is speculation that this is related to the paler skin of the soles, palms nailbeds and mucous membranes, where there are more melanocytic naevi than in other sites.[31]
C. 4 Summary of the different histological types of melanoma
Of the different types of melanoma, the SSM is particularly important because of the
following features:
•
they are the most common;
•
they have a phase of growth that might allow them to be identified and removed before
they threaten life by distant spread;
•
They are often indistinguishable from common banal naevi on the skin.
C. 5
Distribution on the body
In white races, the most common site for melanomas in women is the legs, and in men the
trunk.[32] For example, a Western Scotland series of 180 patients with melanoma showed that
the site was the legs of women in 63%, and in men the trunk in 34%.[33] In Sweden, using a
national register of 3 888 melanoma over 25 years, the rates were 24% ('lower extremity' of
women) and 38.6% ('trunk of men') respectively.[34]
— 13 —
C. 6 Prognosis of melanoma
There are many influences on the prognosis of melanoma. The importance in discussing this
becomes apparent in deciding on several factors, including the width of the margin of the
excision away from the edge of the melanoma, and in attempting to improve the prognosis by
changes to the management of melanoma.
The prognosis is adversely influenced by being older, male, having the lesion on the central
body rather than the limbs, and of course having metastases distant from the primary site on
the skin. More important factors are the level of invasion of the melanoma (the Clark Level),
and its thickness (the Breslow thickness). The latter appears to be the best single guide to
prognosis, particularly to early non-metastasised lesions. The area has been reviewed, Figure
I.1.[29]
100
90
80
70
60
50
40
30
20
10
0
² 0.75mm ² 1.49mm
² 2.49mm
² 3.99mm
Thickness of tumour
Stage
³ 4mm
III
II
I
Confined to skin
Nodal
Dis tant
met astases
met astases
Figure I.1 The relationship of staging and melanoma thickness with prognosis (after data in
Koh in 1991) [29]
Melanomas which are thin (≤0.75mm) treated by simple excision will have an excellent
prognosis. The importance of this is that:-
•
the cure of a major malignancy, without referral (except to pathology services) comes
into the reach of general practice.
— 14 —
•
if the model described above (Section C 2) is correct with respect to the progression of
radial-growth phase lesions moves towards a vertical growth phase in a progressive
manner with time, then removing melanomas early might improve the prognosis
dramatically. This has implications for the management of melanoma which will be
addressed in Chapter IV.
D. Aetiology of skin cancer
The aetiology of skin cancer is important in the discussion of how best to prevent it. There are
two broad groups of factors:
•
environmental and host factors associated with sunlight on the skin causing NMSC and
melanoma; and
•
the effect of naevi on melanoma.
D. 1. Sunlight and skin type
The importance of sunlight in the genesis of melanoma and NMSC is firmly established in the
literature. This has led to a model for the genesis of skin cancer. In a simplified version of this
model there is a promoting event and a potentiating one. Sunlight is advanced as the principal
candidate for both roles.[32, 35] Evidence comes from several types of study:-
D. 1. i Environmental comparisons
The differences between the incidence figures between different countries and
between different areas within countries may be explained by differences in the
intensity of solar radiation.[15, 17, 36]).
D. 1. ii Behavioural
People in any one environment are exposed to different levels of solar radiation
because of differences in recreation or occupation. Good evidence that increased
solar radiation exposure is associated with increased incidences of NMSC and
melanoma comes from case-control studies.[35, 37-51] They have been reviewed
comprehensively.[15] The conclusions is that both NMSC and melanoma are
associated with solar radiation, almost certainly casually. The relationship
between solar radiation and NMSC is more direct than that for melanoma.
— 15 —
D. 1. iii Constitutional factors
The fairness of the skin, hair and eye colouring, tendency to freckle and ability to
tan in sunlight are associated with propensity to both melanoma and NMSC.
Those with red hair, green eyes, fair skin and hair, poor ability to tan and
tendency to freckle in sunlight are more likely to develop both NMSC and
melanoma. [1, 35, 37-52]
Another constitutional characteristic involves the influence of acquired
melanocytic naevi. This characteristic is important in predicting those at risk of
melanoma. Because it is part of a very complex and important effect, it is
addressed in more detail (Section D. 2. P19).
D. 1. iv
Childhood sunlight exposure
Migration studies of people moving from countries of low to high incident sunlight suggest
that protection against sun-exposure in childhood (defined as up to the age of 10 years of age)
is associated with a lower than expected incidence of melanoma in later life[5, 46], as well as
NMSC.[5, 53] ) This fits into the simple model described in D. 1. above. According to this
theory there is a are at greater risk from the initiating effect of sunlight during childhood as a
carcinogen. The effect of sunlight as a promoting carcinogen (in adulthood) is less important.
Therefore people are relatively protected against skin cancer by avoiding solar radiation
during childhood.
D. 1. v
Deciding if the association between sunlight and sun cancer is causal
Although the evidence that the association between sun exposure and NMSC is well known,
the association is not straightforward.
There is evidence that for some NMSC, increasing sun exposure may act to protect people
from skin cancer in some situations. A case-control study of the factors associated with BCC
showed that the odds ratios of BCC on the head and neck (but not other sites) decreased with
increasing exposure to sunlight. For all sites, using sunlight as a continuous variable, there
was a peak incidence of BCC (OR=1.4) at 35,000 hrs exposure, followed by a fall. Beyond a
certain exposure of sun exposure, the risk of BCC is not increased further and may actually
fall.[54]
For melanoma the association between sunlight and aetiology is more complex. Places with
high latitudes have a higher incidence of melanoma than expected by a simple theory of
— 16 —
sunlight-causing melanoma. For example Sweden and Norway have higher incidences than
many less Northern countries.[51]
Case-control studies of sun-exposure show that in people who have been exposed to high
levels of sunlight the incidence of melanoma is lower than expected. There is conflicting
evidence coming from Germany[48], Denmark[55], Canada[36, 56], and the UK[40, 42], as
well as Australia.[5, 57, 58] They have been reviewed.[17, 29, 39] Sunlight was initially
thought to increase the risk by triple for recreational exposure, but only by double for
occupational exposure. This is counter-intuitive because occupational sun exposure carries a
greater exposure to sunlight.
A more recent systematic review concludes that occupational exposure actually protects
workers from melanoma, with a relative risk of 0.86.[59] Intermittent exposure to sunlight
may be more harmful than continuous, as with occupational exposure.[15, 59] The possibility
that some groups of people are protected by developing a sun tan has important implications
in the consideration of primary prevention (see Chapter V, where this argument is taken up
further).
It is important to note that sunlight is not the risk factor with the greatest effect. That appears
to be related to the number and type of melanocytic naevi on the skin, (see below).
Nevertheless sunlight is important in terms of possible prevention because it is the only risk
factor subject to modification.
A case control study undertaken in Germany Belgium and France by the European
Organisation for Research and Treatment of Cancer of 420 cases and 573 controls showed that
regular sunscreen use was associated with an odds ratio of 1.85 (95% confidence interval of
1.3-2.6) for regular sunscreen (adjusted for age, sex, hair colour, the number of holidays in
sunny climates, and awareness about the dangers of sunlight).[60] This effect was also
observed in Sweden where an odds ratio of 1.8 (95% confidence interval 1.1-2.8) was found
for the use of sunscreen and subsequent risk of melanoma in another case-control study of 400
melanoma cases and 640 controls.[61]
There are several principal ways of deciding whether the relationship between two associated
factors is causal or not. One is to test the strength of association in an experiment: if applying
or removing the risk factor results in a different level of outcome this is very good evidence.
Another way is to examine the credibility of the biological mechanism. If a plausible
mechanism for the process (meaning one which accords with current thinking) can be found to
explain the characteristics, this offers broad support for a model of an illness causality.[62, 63]
— 17 —
No experimental study has been devised with respect to preventing skin cancer by reducing
sunlight. This would involve a randomised controlled trial, with avoidance of sunlight as the
intervention and skin cancer as the outcome variable studied. However evidence comes from a
surrogate in the form of a randomised controlled trial in which use of sun-cream as the
intervention was compared against control, with the outcome being the number of solar
keratoses that developed. The incidence of solar keratoses decreased in the intervention group
compared to the control group, (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71)
and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80).[64]
Although sun damage and the development of solar keratoses are risk factors for the
development of melanoma, they are relatively weak markers.
More sophisticated models have been assembled to explain the complex relationship between
melanoma and sunlight. One addresses the confounding behaviour of people with sunsensitive skin avoiding the sun which thereby reduces their exposure to the risks of melanoma.
— 18 —
sun sensitivity
-
+
+
sun exposure
+
sunburn
sun exposure
melanoma
+
Figure I. 2. Confounding between sun sensitivity, sun exposure, sun exposure and the risk of
melanoma. Adapted from Armstrong.[15] The summary of a theoretical
mechanism by which melanoma may be caused by sun exposure and sensitive
skin, compensating for the fact that people with sensitive skin may reduce their
exposure to sunlight, and therefore to the risk of melanoma. This will make it
more difficult to predict which people will be at higher risk of melanoma on the
basis of their exposure to sunlight (for example occupational classification) and
their skin type. In this model, sunburn is not a direct link in the chain between
sun exposure and melanoma generation; rather it is a biological marker for sun
exposure and sensitivity, both of which are direct causes of melanoma.
A development of the simplified theory (Section D. 1.) forms the basis for the 'intermittent
exposure theory', summarised by Armstrong.[15] In it, intermittent exposure to sunlight
causes greater risk to melanoma than continuous exposure because of the protective effect of
tanning. Tanning, it is proposed, protects the skin from melanoma. Since some people tan
poorly in response to solar radiation they cannot acquire this protection as readily as those
who do tan easily.
Support for this theory comes from a case-control study from within the Nurses Health Study
in the USA, in which, from a sample of 121,700 women born between 1921 and 1946, the risk
of trunk melanoma was examined. Although bikini use did not cause an increase in melanoma
on the trunk, sun-sensitive women were more prone if they had high swimsuit use behaviour
at ages 15-20 (RR 6.4; 95% CI 1.7-23.8; p<0.01). However there was a trend towards
protection of women who were sun-resistant (RR 0.3; 95% CI 0.1-1.0; p=0.06). This suggests
that women who are sun-sensitive may increase the risk of sun-light on the skin directly, while
sun-resistant women may be protected—presumably by tanning.[65]
— 19 —
Different susceptibility of melanocytes to neoplastic change is another model invoked to
explain the differences in susceptibility of different sites of the body to melanoma.[66]
In conclusion it appears that sunlight is a very important carcinogenic factor. However its
influence on causing melanomas is far from simple or linear. The processes by sunlight
causing melanoma is by no means established, but there is enough evidence to suggest that
populations should avoid sunlight.[67, 68]
However there may even be situations in which sunlight protects some individuals from
melanoma. This has important consequences which will be returned to in Chapter V when
primary preventive measures are considered.
D.2. Naevi
The importance of naevi as a risk factor for melanoma has been referred to briefly as a
constitutional factor, (Section D. 1., p15). Two separate effects must be summarised. The first
is that the presence of banal naevi is a risk factor for melanoma.
D. 2. i Benign naevi
Benign naevi (also variously described as common, banal, and melanocytic naevi) appear to
act as risk factors for developing melanoma. This is such an important phenomenon that some
space will be devoted to examining this.
A case-control study conducted in Scotland (Glasgow and Edinburgh) showed that there was
an increased risk for 131 people in whom melanoma had been reported compared with 108
controls. The relative risk was 20 (95% CI 5-181, adjusted for other risk factors such as hair
and eye colour, skin type and exposure) for patients with ≥25 benign naevi.[69] This casecontrolled study was modified and expanded to 180 cases and 197 controls. It showed that the
relative risk was 54 (95% CI 18-159) for patients with ≥50 naevi when adjusted for hair and
eye colour, skin type and amount of skin exposure.[33]
Another case control study of 207 patients with melanoma and 295 controls found a relative
risk of 19.6 for more than 120 naevi on the body.[70]
Other case-control studies have found lower relative risks from naevi: for example in Sweden
it was (adjusted odds ratio) 2.6 for >149 benign naevi (total body) compared to <76.[51]
Thus although the exact level of risk is not established, the presence of common banal naevi is
a risk factor for developing melanoma. The risk factor appears to be higher (possibly much
higher) than for other factors such as sun exposure.
— 20 —
D. 2. ii Atypical naevi
Strongly inherited forms of atypical naevus
It became clear in the late 1970s that some naevi were associated with greater risk of
melanoma than others. Early descriptions focussed on two families (whose names began with
the letters 'B' and 'K') with an inherited form of very high incidence melanoma. [71] The term
'B-K' naevi was changed to 'dysplastic' naevi because it was thought they might represent a
precursor to melanoma. As is seen in the discussion below, there is doubt about this. In
consequence, at an international conference held by the National Institute of Health in the
USA it was decided to offset any confusion in the use of the term by using the more neutral
expression 'atypical naevus'.[72] Although serious for those inheriting the disorder, there are
indications that 'dysplastic naevus syndrome' does not account for many of the melanomas
that are encountered in any series: a large meta-analysis of eight case control studies examined
the family histories of 2 ,925 patients with melanomas, and controls. It concluded firstly that
risk of melanoma from a positive family history is not heterogeneous (which would be
expected if there was a large separate atypical naevus syndrome).[73] This suggests that few
GPs will encounter the inherited form of the illness. Secondly the increased risk from a
positive history of melanoma from a first degree relative was only 2.3 (95% CI 1.762.86).[73]
Less strongly inherited forms of atypical naevus
The term atypical naevus denotes irregularity at either the pathological (histological) or
clinical level. Histological criteria of atypia (there are two major and four minor criteria)
appear to be reliable between different pathologists in the international arena.[74] Clinical
manifestations of atypia include being large (>7mm for example), having colour variation, or
having an irregular edge.[75] For those whose benign naevi possessed different atypical
characteristics, the relative risk was modified as follows: with colour variation (relative risk of
11, 95% CI 1.5-82); irregular edge (relative risk 15, 95% CI 1.8-119); and possessing large
naevi (>7mm diameter), (relative risk for ≥5 large naevi of 4, 95% CI 0.3-57).[69] In the
modified and expanded case-control study for patients with lesions which were characterised
by being ‘clinically dysplastic’, that is ≥5 benign lesions larger than 7mm, the relative risk of
6; 95% CI 1.5-21), possessing lesions with colour variation, (relative risk of 30, CI 7-123);
and with an irregular edge (RR=70; 95% CI 10-518), when adjusted for hair and eye colour,
skin type and amount of skin exposure.[33] Lower risks were estimated from a later Swedish
study (relative risk of 2.5 and 5.6 for 1-2 and >2 dysplastic naevi respectively).[51]
— 21 —
D. 2. iii Do naevi evolve into melanomas?
There are several models in the literature of non-malignant tissue being precursors of
malignant tissue, for example, cervical intra-epithelial neoplasia (CIN) lesions of the
cervix[76] and the mucosal polyps of the colon.[77] The notion is that a benign lesion (in this
case a benign naevus) changes with time into a malignant one (in this case a melanoma). This
question is important because of the potential to intervene with benign lesions. It might be
thought prudent for example to excise benign naevi from people to prevent melanomas
developing in them.
The question has been addressed by several authors. A study of over 1,000 melanomas were
examined histologically to look for evidence of a pre-existing naevus within the specimen.
Only 23% of melanomas had associated benign naevi evident.[78] On the other hand in a
separate study of 289 small melanomas, a naevus was associated with the melanoma in 51%.
Most (56%) were atypical naevi, 41% were common acquired naevi, and 3% were congenital
naevi.[79]
Thus at least some melanomas appear not to develop from pre-existing naevi, although they
may arise more often from other melanocytes in the surrounding tissue.[79] Certainly doubt
has been cast on the oncogenesis of all melanomas from benign naevi. Naevi may be simple
markers of disease risk without being directly part of the process[75, 80] For example the
association of the transverse ear-lobe crease with ischaemic heart disease is unlikely to be
causal.[81] Thus no-one has advocated plastic surgery of the ear lobes to improve risks of
ischaemic heart disease.
Even if a substantial proportion of melanomas evolved out of naevi, the numbers of naevi
would pose a problem for their prophylactic removal: The number of naevi on any individual
is high, although difficult to define mostly because of different definitions of 'naevus'. It varies
considerably with time.[82] The number of naevi drops during adulthood following a
maximum of about 22 (males) and 33 (females) in the third decade of life (counting only
naevi larger than 3mm).[83] More recent counts estimate different numbers, possibly partly
related to different definitions of what was counted. For example in New Zealand, the mean
number more than 2mm was 24 in adolescents around 14-15 years of age in Dunedin.[84] The
range among 2,595 children (≥ 2mm) in Western Australia was 96 for girls and 120 among
boys.[85]
The large number of naevi (at any one time) and the fact that their appearance and
disappearance is dynamic poses a problem for the principle of removing them because this
would pose an astronomical burden on medical services, quite apart from not preventing a
— 22 —
considerable (but unknown) proportion of melanomas from developing.
D. 2. iv Conclusions about naevi in general practice
The numbers of benign and clinically dysplastic naevi are important risks for melanoma.
These two risks are not independent: there is an association between numbers of benign naevi
and dysplastic ones, stronger among those who develop melanomas.[51]
The problem naevi pose in the diagnosis is explored in Section E.
D.2 Other risk factors
Another factor that has been considered is that of diet. This is important because of the
potential to modify risk factors. Some work suggests that diet may be an important factor. For
example, a low fat diet was shown to be associated with a lower incidence of non-melanocytic
skin cancer.[86] On the other hand a case-control study showed that being overweight was
protective.[37] Diets high in beta carotene and vitamin E, as well as fish-oils, appear to
reduce the relative risk of melanoma.[87] However although there are no studies yet
published to establish the role of diet in protecting people against developing melanoma, (such
a trial is in progress in Queensland as part of the Nambour Intervention Trial of diet against
Melanoma, using supplemental beta carotene), the results of other observational studies have
not encouraged work in this area.[35, 88]
Other risk factors not associated with the modified sunlight theory include exposure to
fluorescent lights and hormones effects. Although both have been studied, any effect from
these, if they exist, are not large enough to suggest public heath measures to modify the
risk.[32]
E.Diagnosis of melanoma
On the face of it, melanoma should be easy to diagnose. It is usually contrasted in black
pigment on the surface of the skin, and therefore should be easy to access.[89] The model
described in Section C. 2. a. suggests that melanomas may transform from a horizontal growth
phase (with a good prognosis) into a radial growth phase (with a less good prognosis). There
is enormous pressure on the clinician to identify lesions early and not delay diagnosis.
E. 1. Differential diagnosis
However there are other skin lesions that can be confused with melanomas. They include most
especially benign naevi (including dysplastic naevi) and other non-melanocytic pigmented
— 23 —
lesions such as seborrheoic keratoses.[52] The presence of multiple naevi on the skin of white
people poses a challenge to the diagnosis of melanoma.
There is a list of characteristics that distinguish naevi from melanomas. These characteristics
have been weighted according to their ability to predict melanoma, the so-called Glasgow
'seven-point rule', in order to assist people identify melanomas from banal pigmented lesions
(particularly naevi).[90] They can be listed as three major characteristics: asymmetry of the
edge of the lesion, its colour variation, and surface characteristics, (particularly a change in
these); and four minor characteristics: being greater than 7mm; the development of satellite
lesions; symptoms such as bleeding or crusting; a sensation (itching for example). Similar
characteristics have been developed in the USA with slightly simpler format (the 'ABCD'
rule).[91].
E. 2. Multiple naevi
Individuals who have greater numbers of naevi are more likely to suffer melanoma, (see
Section D. 2. i. above). Graphing the distribution of naevi numbers against numbers of people
shows that the curve has a very long tail to the right. For example the median is only 18 for a
mean of 24 among adolescents in New Zealand.[84] This means that a minority of people
have very large numbers of naevi. They are those who are at greatest risk of melanoma. The
fact that those with the most naevi are more likely to have melanoma makes diagnosis more
difficult.
E. 3. Atypical naevi
The possession of atypical naevi has been described above as conferring a greater relative risk
to the development of melanoma than banal acquired naevi (Section D. 2. ii). Unfortunately
the clinical characteristics that distinguish atypical naevi from banal acquired naevi are very
similar to those that distinguish either from melanomas (see Section E. 1). In other word the
discriminating characteristics of the lesions which are conferred on people at highest risk of
melanoma (atypical naevi) are the most difficult to separate clinically from them.
E. 4.
Distinguishing SSMs from melanomas
SSMs have been described (Section C. 6) as being lesions with a good prognosis if they are
thin (particularly <0.76mm thick). Most melanomas with a horizontal growth phase (with a
good prognosis) are SSMs. Unfortunately these are also the type of melanomas which may be
most clinically like banal naevi. This is particularly true for the smaller and thinner
melanomas. This means that the melanomas which clinicians are anxious to diagnose and treat
definitively—those still with a good prognosis—are those most like banal lesions. Indeed
some may be indistinguishable from common naevi.
— 24 —
E. 5. Clinical performance in diagnosis
From considerations of the issues described in the above (Sections E. 1. to 4.) it could be
predicted that clinicians have difficulties managing pigmented skin lesions under suspicion of
being melanomas.
One line of investigation has been to estimate clinicians' ability to distinguish melanomas
from naevi and other lesions. This poses several methodological difficulties. Ideally clinical
ability to distinguish benign from malignant skin lesions would be tested by asking clinicians
to make clinical diagnosis of lesions on patients who are having the lesions diagnosed by a
gold standard. This gold standard is usually taken as the histological diagnosis. Pathologists
have achieved a high degree of agreement on the diagnosis of melanomas, reaching a
concordance of 92% typically.[74] On this basis using the pathologists as a gold standard will
appear to be reasonable.
Some series have estimated the frequency of lesions not suspected of being melanomas which
were excised and subsequently discovered to be melanomas on histological examination. In
one series of 1,784 lesions excised but thought on balance clinically to be benign by specialist
dermatologists and surgeons, 33% were found to be melanomas: 159 were pre-excision
thought to be naevi; 63 to be BCCs; 45 to be seborrhoeic keratoses; and 44 to be lentigos.[92]
This suggests that the false negative rate of diagnosis might be high. Clearly some melanomas
are very difficult to diagnose. For example in a series of 178 melanomas the diagnosis of
melanoma was not entertained in 13. Eight were amelanotic melanomas (long recognised as
the most difficult lesions to identify).[93]
A study of benign naevi followed prospectively before excision examined two versions of the
Glasgow seven-point scale. It found that specificity was as low as 70%.[94] It has been argued
of course that high sensitivity is much more important than high specificity in the diagnosis of
melanoma.[90]
There have been several examinations of the characteristics of the lesions removed and
submitted for histology. For example in one series from North America of 2,935 melanocytic
lesions, 23% were atypical naevi; and only 1% were melanomas. Dermatologists and plastic
surgeons had the highest diagnostic accuracy.[95] In an Australian series of 1277 lesions
there were 72 melanomas (6%) and 14 atypical naevi (1%).[96] In neither of these cases were
there estimates of the proportions of lesions that were removed to exclude malignancy rather
than for other reasons. Nor was there any estimate of the different proportions excised for
each age and sex group.
— 25 —
The specimens of melanomas removed by GPs in two settings have been studied. In the
Netherlands, 237 melanomas excised by GPs were thinner than the national average,
suggesting to the authors that GPs find them earlier.[97] Similar results were found in another
series from Scotland, (where the authors also offered criticism that that the excision margins
were less adequate and GPs were more often surprised that the lesion was a melanoma).[98]
Comparing hospital and community management is not a good method of studying the
performance of general practice in melanoma management because of the potential for
selection bias. GPs may be more likely to refer clinically larger and thicker melanomas for
specialist care.
Another line of investigation has been to study the events that take place during the diagnosis
of melanomas. Firstly most melanomas are brought to the attention of medical treatment by
patients. Melanomas were found by GPs noticing the lesions first in 23% of cases, and more
often (26% of cases) with SSMs.[19] Women identified melanomas on themselves more
frequently than men. Similar results from an American study of a mail-based survey of 216
people with diagnosed melanomas found that doctors discovered 26% of the melanomas
opportunistically.[99]
A study was undertaken of people in the Australian community with regard to symptoms that
might suggest melanoma. Out of 1,344 individuals, 156 (12%) had observed signs in the
previous 12 months that might suggest melanoma, of whom 32% had seen a GP about this,
and of whom 5 (3%) reported finally having had a melanoma diagnosed. This number is too
low to allow analysis of any delay that GPs may have contributed. Nor is it clear whether
respondents were asked whether any lesions were identified first by their practitioners.
However the study did allow some estimate of the rather poor response (only one third) of
people to respond to signs of possible melanoma.[100] In the UK, 125 patients with
melanoma were questioned about reasons for delay in diagnosis. Although only 16% were
excised in less than 3 months, in only 3 did the GP even partly contribute to delay.[101] In a
somewhat similar South African study, 250 consecutive patients with primary cutaneous
malignant melanoma were investigated. Mean total delay from the onset of observed change
in a melanoma to appropriate therapy was 11.1 months. The major component of delay (9.8
months) was patient related. Seventy-nine (31.6%) patients waited more than 6 months before
seeking medical attention. Few patients recognized early melanoma, and 46% responded only
to late features (i.e., ulceration or bleeding). Inappropriate professional delay (misdiagnosis or
observation without specific action) occurred in 30 consultations (12.4%) and resulted in an
overall further 1.3-month mean delay in treatment.[102]
Another approach has been to look at the performance of clinicians under artificial conditions.
— 26 —
In one such study 106 junior hospital doctors and 48 dermatologists were shown pictures of
11 skin lesions. The junior hospital doctors were less accurate at diagnosing pictures of
melanomas than the specialists.[103] A similar questionnaire-based study of GPs attending a
conference was undertaken in the USA. The GPs were shown slides of skin lesions. Their
sensitivity for identifying the melanomas was 0.88 compared with specialists at 1.0.[104]
There are theoretical problems with such a methodology. It may not be possible to generalise
with any certainty about clinicians' ability from their performance with just a picture of a
lesion to examine. They are denied the subtleties of the history, the texture to palpation, the
ability to stretch the lesion with the examining fingers[105], and to examine the lesion from
different angles. There are additional problems with concluding that specialists are better
diagnosticians than GPs from these studies. The ratio of different pathological groups among
the lesions 'examined' (the 'casemix') is often different to those offered the clinician in a real
situation. This a particular problem for those working in clinical settings which encounter
melanomas at different incidences. Thus dermatologists will be more likely to be clinically
accurate if they offer a diagnosis of melanoma more often than a non-specialist if shown a
series in which the melanoma rate is close to that in a specialist referral clinic (as in this study)
than in a non-referred population. (Conversely GPs will be more likely to be correct if they
offer a diagnosis of 'benign' when shown a series akin to their own practices with very few
and rare numbers of malignancies, and indeed specialists in community settings do perform
less well[106]). A study in Australia showed that GPs who were educated in the diagnosis of
melanoma improved their ability to identify pictures of melanomas. However no change in
their clinical ability (by studying their excisions patterns) was discernable.[107]
A similar study by a group in Victoria can be criticised for some of the same reasons: a
questionnaire with photographs was mailed out to 666 GPs. The sensitivity for the melanomas
and other skin cancers among the photographs was only 0.61. Nevertheless useful information
was obtained: the investigators demonstrated how the correct diagnosis predicted correct
management. That is, the critical point with melanoma management is diagnosis. They also
established that small and thin melanomas ('early') were more difficult to diagnose than
vertical growth and larger lesions.[108]
The best diagnostic performance might be expected to be encountered in specialist clinics. In
one such clinic dermatologists diagnosed 214 melanomas out of 13 878 lesions referred. The
sensitivity from this was 0.85, with a specificity of 0.99.[109] Because it is not possible to
estimate how many lesions were not excised (because they were thought to be benign, and not
removed within the time period of the study) the estimated specificity can only be crude from
such series, and likely to be over-estimated.
— 27 —
An attempt to establish these 'missed melanomas' came from another specialist clinic study.
Three London dermatologists were asked to each examine 120 lesions thought initially by at
least one of them to be benign clinically and then submitted to biopsy. Three were found to be
melanomas. The small flat pigmented lesions caused the greatest difficulty. (For example
seborrhoeic keratoses were the most accurately diagnosed). The specificity ranged between
0.75 - 0.83 for the different lesions.[110]
The aspect of diagnosis of melanoma in general practice is explored in more detail in Chapter
III.
Excision margins
The treatment of small ('early') melanoma is essentially excision.[111] The size of normal
tissue to be left around melanomas excised is an issue because if the margin is very large then
the surgical procedures required to close the wound satisfactorily puts the management of
melanomas beyond the capacity of most GPs.
Standard texts emphasise the requirement of ensuring an adequate margin of normal tissue
surrounds the lesion.[2, 52] This approach comes from very early work, summarised by
Davis.[112] The poor prognosis in early historical management of melanoma led to the notion
that cells might contaminate normal tissue and lead to local and distant metastases.[113] It
became established practice to remove a large piece of skin and deeper tissue often as wide as
5cm around the margins of the melanoma. The practice often required complex surgical
procedures to close the wound, consequent functional disability, and poor cosmetic results.
This has been challenged.[112]
An observational study in Western Australia found that over 6 years among all the melanomas
removed, 35% had been subject to an excision margin of less than 1cm. Their survival was
slightly higher than those whose excision margins were ≥2cm and their chance of local
recurrence slightly higher, but neither were significantly different. Such a study can be
criticised because of the potential for selection bias (patients with features of poor prognosis,
other than those for which there were attempts to correct, might have been offered wider
excision).[114]
However there have been at least three randomised trials, the ideal method of testing this idea.
A trial of 612 patients with thin (≤2mm) melanomas compared narrow excision (1cm margins)
with wide excision (≥3cm). They were followed for a mean of 4.5 years. The difference in the
— 28 —
metastasis rate (6.9% and 9.1% respectively) was not significantly different. However there
were 3 local recurrences in the narrow margin excision group and none in the wide.[115]
A similar multicentre trial compared narrow excision of 2cm margins around thicker
melanomas (up to 4mm thick) among 305 patients with wide excision (≥4cm). They were
followed for a mean of 6 years. The difference in the metastasis rate (2.1 and 2.5%
respectively) was not significantly different. Nor was the difference in local recurrence rate
(0.8 and 1.7% respectively) significant.[116] Similar findings were established for a Swedish
trial of 769 patients.[117]
It seems that narrow margins around the melanoma confers no appreciable risk for recurrence.
This puts the definitive treatment of thin and small melanomas into the reach of many GPs.
F. Conclusions
There are several sets of conclusions relevant to general practice.
There are two sorts of skin cancer that should be addressed because of either their work-load
burden (NMSC) or because of their danger (melanoma). Both are addressed in the thesis,
melanoma especially in relation to prevention and early detection, and NMSC especially in
relation to prevention and workload.
Sunlight appears to be an important factor in relation to the generation of skin cancer of both
NMSC and melanoma groups. The potential for reducing the solar radiation falling on the skin
will be explored in Chapter V.
It is possible to predict that naevi pose a significant difficulty for clinicians because they can
resemble melanomas closely. Moreover they are more common among those in whom
melanoma is a higher risk. Chapters III and IV addresses this aspect of the general practice
management of skin cancer.
Diagnosis and definitive management in the form of excision biopsy are often identical for
small melanomas. Since modest surgical techniques are able to definitively treat small and
thin melanomas, and since these are most commonly encountered melanomas, then the
definitive treatment of thin and small melanomas lies within the reach of many GPs. NMSC
with its less serious potential is also amenable to complete management within general
practice.
— 29 —
However it is not clear to what extent this is exercised by GPs in Australia. Chapter II
addresses this question.
— 30 —
Chapter II
Skin cancer from the perspective of Australian general practice
A Introduction to the issue
This chapter contains estimates and descriptions of the work-load of skin cancer on Australian
GPs. Australia has the highest recorded incidence and prevalence of skin cancer in the world.
Australia has a gatekeeper general practice system (whereby patients can only gain access to
Medicare funded specialist medical practitioners, including dermatologists, by referral
through a GP). Therefore the impact of any medical condition will influence GPs, whether
they or another discipline of the medical profession have ultimate responsibility for that
condition. In addition, if GPs manage skin cancer mostly without referral to specialist
services, then the workload might be large.
The size of the Australian general practice workforce
There are 39,811 medical practitioners billing Australian Medicare of whom 43.6% (17,358)
are GPs.[118] This implies a ratio of about 1000 (of the 18.3M[119]) Australians eligible for
Medicare to each GP. However since many GPs are part-time, this figure should be adjusted
upwards. These estimates range from one full-time equivalent GP (or, more accurately, nonspecialist medical practitioner) to 1,043 Australians (capital cities) to 1,745 Australians (in
some rural settings). Most GPs care for a mean of fewer than 2,000 people.[118]
Implications of the workforce calculations on the frequency of encountering different
diseases
A disease as infrequent as an annual incidence of 1:1 000 000 means that any GP will be
involved in the initial management of the condition on average less often than once every 500
years (1 000 000/2 000). On this basis tumours that are neither non-melanocytic skin cancers
nor melanomas are regarded as sufficiently rare to be considered no further.
Melanoma and non-melanocytic skin cancer from the perspective of Australian general
practice
There is little published in this area. A search of the literature at the time of conducting the
study reported in this chapter failed to discover any relevant data relevant to either Australian
or international primary medical care.
Two sources of data were available at reasonable cost. These are described below.
— 31 —
II B.
Australian Morbidity and Treatment Study (AMTS)
II B. 1
Introduction to the AMTS method
The Australian Morbidity and Treatment Study (AMTS) was the largest funded descriptive
study of Australian general practice workload. A condition of the funding was that the data
collected should be made available for further analysis by others. In collaboration with
Associate Professor John Lowe as part of a program of research into the behavioural aspects
of skin cancer reduction, some of the data were studied to analyse the skin cancer from an
Australian general practice perspective.
II.B 2.
Source of the data from the AMTS
The AMTS has been described in detail.[11] In brief, randomly selected GPs across Australia
were invited to record their consulting activities twice for a fortnight during a one year period.
A response rate of 50.4% meant that 495 GPs participated sufficiently to be included. All the
times of the year were sampled to allow analysis of possible seasonal differences. GPs were
asked to record at every consultation details of the patients' demographics, reason for the
encounter, diagnosis, investigation and management. A distinction was made between 'new'
and 'subsequent' presentations to allow estimates of both prevalence and incidence.
Research assistants later transcribed the data into a database for analysis. They coded the
reasons for encounter and diagnoses using the International Classification for Primary Care
(ICPC).[120]
IIB 3.
Coding the AMTS data
The AMTS attempted to code every reason for encounter and condition detected by the
recording GPs. The ICPC is a branching tree classification system. Diagnoses can be
differentiated within it more or less into specific conditions depending on diagnostic certainty.
The data were coded in such a way that broad diagnostic labels were employed. This meant
that some fine detail was sacrificed during coding (by 'lumping up') to allow comparisons of
data from sources in which less fine detail had been recorded. Of the clumps of diagnosis
groups there were three that appeared to fulfil our requirements of describing the skin cancer
workload:—
'Malignant skin neoplasms'
They encompass all skin cancer, including melanoma, SCC, and BCC, but also metastatic skin
cancers from other parts of the body. This is an unsatisfactory grouping for several reasons.
— 32 —
The groupings fail to differentiate between primary skin cancers arising from skin tissue, and
sarcomas, lymphomas, appendageal tumours and other cancers which metastasise to the skin.
However the incidence of non primary skin cancer is rare in comparison with melanomas and
non-melanocytic skin cancer (NMSC) which are made up of SCCs and BCCs.[2]
The grouping fails to distinguish between important groups of primary skin cancer. The
discrimination of greatest interest is that between melanoma and non-melanocytic skin cancer
(because of the important difference in prognosis between these two groups). There seems to
be no solution to this for the following reasons. Doctors will often manage the skin lesion in
question without having hazarded a diagnostic guess as to the final histology. For example a
lesion which on clinical appearance resembles a superficial BCC or SCC might be treated
with ablation cryotherapy without ever being subject to final histological confirmation.
Confirmation of diagnosis may not be necessary to the successful management of the lesion,
although there may be cases of benign lesions treated unnecessarily vigorously. In particular
the management of naevi and melanomas may be impossible to discriminate between.
‘Naevus/Mole’
This definition was included on the assumption that much of the management of these lesions
(melanocytic naevi, or 'moles' in common parlance) is related to differentiating them from the
melanomas they resemble. There are several potential problems with gathering data grouped
in such a way:Not all melanocytic naevi are managed in general practice in relation to skin cancer.
Sometimes the problem is for other concerns: cosmetic concern; irritation (perhaps against
clothing); and other reasons. These will be separate from any interest in skin cancer.
Even when considering the differentiation of naevi from melanoma, the choice of the term
'naevus/mole' and ‘malignant skin neoplasm’ that GPs would select to describe the reason for
encounter may be unreliable: either term might be used to describe the same phenomenon.
That is different GPs might select different terms to describe the same phenomenon.
‘Other benign skin neoplasms’
This heterogeneous group was included to compare with the other two diagnoses. This term
suffers the same drawbacks:Not all 'other benign skin neoplasms' are clearly benign: a number will be presented because
of concern that they are malignant.
In these cases, when considering the differentiation of 'other benign skin neoplasms’ from
'malignant skin neoplasms', the choice between the terms 'other benign skin neoplasms’ and
— 33 —
'malignant skin neoplasms' that GPs would select to describe the reason for encounter may be
unreliable: either term might be used to describe the same phenomenon. That is, different GPs
might select different terms to describe the same phenomenon.
Useful comparisons were anticipated between these different diagnoses and the demographic
characteristics of the patient; their place of latitude in Australia; the associated other medical
conditions; and different forms of management. Comparisons may be valid on the assumption
that whatever biases exist in the recording of the lesions will be equal for the different
comparison groups.
IIB 4. Analyses of the AMTS data
Data were available from the AMTS team in the form of 'new' conditions and 'all' conditions.
The difference between these is that respondents were asked to nominate whether or not the
condition they were recording was a first presentation or follow-up. Tables of total encounters
of new presentations only, co-existing reasons for encounter, treatments, investigations
performed and the total number of problems managed by age (broken into five age groups)
and sex from the investigators of the AMTS were analysed. The total number of consultations
for general practice in Australia recorded by Medicare for 12 months after October 1990 were
obtained from Tim Burke, Health Insurance Commission, Canberra, (by personal
communication). He obtained these figures by adding together all the exclusive general
practice Medicare Item Numbers: 3, 23, 52, 53, 36, 54, 44, 57, 24, 59, 37, 60, and 47.
The aim was to estimate the absolute numbers of attendance for the three diagnoses in
Australia. The total number of consultations in different age, sex and state categories reported
by the study GPs for each diagnosis (from the AMTS) were divided by the total number of
consultations for general practice (from Medicare). This yielded the proportion of all GP
consultations that took place in the study. Dividing the proportion by an estimate of the
population (from the 1990 census[121]) gave the numbers of consultations in which each
diagnosis was recorded in Australia.
For comparisons between parts of Australia, ages were standardised to the estimated
population in 1990.[121]
IIB 5. Results of the AMTS
The data supplied were weighted for differences in state size by the AMTS investigators.
ADDIN ENRfu [11] All results therefore relate to these weighted data. Skin tumours
accounted for 2 083 (1.5%) out of a total of 145 799 problems that were managed in 98 796
— 34 —
encounters, of which ‘malignant’ skin neoplasms accounted for 986 (0.7%), ‘naevus/mole’
728 (0.5%), and ‘other benign’ skin neoplasms 369 (0.3%). Table II.1 contains the raw data
obtained from the investigators of the AMTS.
— 35 —
Table II.1
Raw data on new consultations for three conditions, and all encounters, by age
and sex.
age
male
female
total
All encounters
≤4
3 967.10
3 457.26
7 721.50
5 - 14
3 990.50
3 793.60
7 932.70
15 - 24
4 134.30
6 445.20
10 713.00
25 - 44
9 369.10
15 559.00
25 268.00
45 - 64
9 338.70
12 312.00
21 920.00
≥65
9 546.90
14 228.00
24 157.00
Total
40 704.00
56 288.20
98 796.20
'Other Benign'
≤4
1.00
2.00
3.00
5 - 14
6.40
10.05
16.45
15 - 24
22.51
16.88
39.39
25 - 44
33.80
46.63
81.37
45 - 64
32.30
46.34
78.64
≥65
11.67
29.64
41.31
Total
107.68
152.54
263.10
'Naevus/mole'
≤4
2.87
2.11
4.98
5 - 14
31.24
25.38
57.09
15 - 24
50.46
52.20
104.53
25 - 44
64.33
107.03
174.27
45 - 64
22.70
54.16
78.02
≥65
17.57
21.01
39.58
Total
193.92
264.75
466.31
'Malignant'
≤4
0.23
0.93
2.09
5 - 14
1.00
0.00
2.00
15 - 24
5.23
2.94
8.17
25 - 44
39.12
37.87
76.99
45 - 64
123.20
91.40
217.54
≥65
161.16
143.16
307.34
Total
332.81
278.30
620.97
— 36 —
Data from the Health insurance Commission (HIC), and the Australian Bureau of Statistics
(ABS) were obtained:Table II.2
Raw data obtained from the HIC and ABS (age groups are collapsed to
match those of the AMTS data)
Age
HIC data of total GP
Data from the Australian Bureau
consultations from October
of Statistics of the resident
1990 - September 1991
population
Male
Female
Male
Female
≤4
4 251 656
3 755 861
645 231
612 921
5 - 14
4 014 376
3 931 906
1 281 313
1 215 529
15 - 24
3 928 480
6 748 326
1 405 949
1 354 814
25 - 44
8 587 995
14 217 607
2 711 736
2 676 459
45 - 64
7 488 073
9 940 616
1 658 484
1 609 311
≥65
5 074 299
9 289 489
808 556
1 084 825
Total
33 344 879
47 883 805
8 511 269
8 553 859
The following formula was used to calculate the number of general practice encounters for
skin neoplasms for each age and sex group:
Calculated number of
general practice encounters
for each age and sex group
Number of reports
for the condition
x
Proportion of consultations
for that category
=
Size of the population
for that category
Where
Proportion of consultations
for that category
Total number of encounters for
that group from the ATMS
=
Total number of encounters
for that group from the HIC
— 37 —
a)
Rates related to age and sex (AMTS data)
The rates of encounter for each diagnosis by age and sex are displayed:-
Table II.3
Calculated numbers of general practice encounters for skin neoplasms per
1000 people annually in Australia by sex from AMTS data
male
female
All 'other benign'
14.6
21.1
New 'other benign'
10.4
15.2
All 'neavus/mole'
28.8
40.9
New 'naevus/mole'
18.7
26.3
All 'malignant'
52.7
42.3
New 'malignant'
32.0
27.7
Females consulted more frequently for benign lesions and naevi/moles than males, but males
more than females for malignant lesions of the skin.
Table II.4
Calculated numbers of general practice encounters for new skin neoplasms
per 1000 people annually in Australia by age and sex from AMTS data
Age group
≤4
5 - 14 15 - 24 25 - 44
45 - 64 ≥65
Overall
'Other benign': male
1.7
5.0
15.2
11.4
15.6
7.7
10.4
'Other benign': female
3.5
8.6
13.0
15.9
23.2
17.8
15.2
'Naevus/mole': male
4.8
24.5
34.1
21.7
11.0
11.5
18.7
'Naevus/mole': female
3.7
21.6
40.3
36.5
27.2
12.6
26.3
'Malignant': male
0.4
0.8
3.5
13.2
59.6
105.9
32.0
'Malignant': female
1.6
0.0
2.3
12.9
45.9
86.2
27.7
The maximal age group consulting with benign lesions was 45-64 years for both males and
females. For naevi/moles it was 15 – 24 years of age, and for malignant it was those aged 65
and older.
— 38 —
Other benign: male
Other benign: female
120
Naevus/mole: male
100
Naevus/mole: female
Malignant: male
80
Malignant: female
60
40
20
0
²4
Figure II.1
5 - 14 15 - 24
25 - 44
Age group
45 - 64 ³65
Calculated numbers of general practice encounters for skin neoplasms per
1000 people annually in Australia by age and sex from AMTS data
The rate of consultations in which ‘naevi/moles’ were managed increased with age,
particularly in females, until the age group 15-24 after which it declined. For ‘other benign’
lesions there was a steady but slow increase throughout all ages. However for ‘malignant’
lesions the rate increased geometrically from very low to high (over 80 encounters per 1000
woman, and 100 per 1000 man, aged 65 or older every year).
b) Associated conditions (AMTS data)
There were one or more other diagnoses in 60% of consultations in which skin tumours were
managed compared with 36% for all consultations; and more than two in about 20%. The type
of skin tumour diagnosed had little effect on the number of other diagnoses reported: a skin
problem (which may have included any skin problem) was recorded as a reason for the
encounter in about 55% of all, and 56% of new, cases of ‘other benign’ skin neoplasms; this
was true also in 61% of both all and new cases for ‘naevus/mole’ diagnoses; and 55% of all,
and 58% of new cases of ‘malignant skin neoplasms’.
— 39 —
c ) Management (AMTS data)
Treatment was mainly procedural (Table II.5). Excisions were more common in encounters in
which the diagnosis of ‘malignant’ skin condition was reported (40%) than in those with
‘naevi/moles’ (28%) and ‘other benign’ skin lesions (23%). Diathermy was more common in
consultations in which ‘other benign’ rather than ‘malignant’ skin neoplasms were reported,
and only rarely among those with ‘naevi/moles’. Cryotherapy was more common among
consultations in which ‘malignant’ rather than ‘other benign’ skin neoplasms were reported,
and only rarely among those with ‘naevi/moles’.
Table II.5 Reports of different procedures by diagnosis from AMTS data
Percentage of consultations
all 'other
all 'naevi / moles' all 'malignant'
benign'
Excision
23.2
27.5
40.2
Diathermy
15.3
1.2
6.0
Cryotherapy
10.3
1.6
20.4
Other*
26.3
18.3
24.8
*'Other' included incision; observation; destruction; use of local anaesthetic; chemical
cautery; removal of sutures; closure of laceration and dressings.
Although a mean of one prescription per problem was written within the overall study[11], the
rate was very much less for consultations in which these three skin conditions were managed,
(1% of ‘naevus/moles’ problems; 6% of ‘other benign skin lesions’ problems; and 4% of
‘malignant’ skin lesions problems). In most consultations for ‘other benign’ skin neoplasms
and ‘malignant’ neoplasms, these were for skin preparations; for those with ‘naevus/mole’
neoplasms antibiotics were the most common broad drug type.
Referral to specialist services was most common during consultations for ‘malignant’ disease
(22%), intermediate for ‘naevi/moles’ (15%) and least common among ‘other benign’ skin
neoplasms (9%). There was a greater proportion of referrals to surgeons (10% of consultations
in which ‘malignant’, 6% ‘naevus/mole’ and 11% ‘other benign’ skin neoplasms were
managed) than to dermatologists (7%, 4% and 7% respectively).
— 40 —
d) Effects of state and territory (AMTS data)
Table II.6
Number of reports of consultations during which three groups of skin
neoplasms were managed, from AMTS data, by state and territory, and the
ABS estimate of the population of each state.
'Malignant' 'Other Benign' 'Naevus/Mole'
ABS Census
ACT
24
23
54
262211
NSW
447
121
261
5834021
Vic
124
106
159
4378592
QLD
283
79
171
2899283
SA
90
24
83
1432056
WA
55
39
47
1613049
Tas
27
20
38
462188
NT
33
8
42
163728
Total
17045128
These data were transformed into the number of consultations per 100 000 people
annually by each state by applying the following formula:=
100,000 x 26 x rate
population
(26 being the number of fortnights/year).
Table II.7
Calculations of rate of consultations during which three groups of
skin neoplasms were managed, per 100 000 people annually from
AMTS data, by state and territory
'Malignant' 'Other Benign' 'Naevus/Mole'
Australian Capital Territory 237.98
228.06
535.45
New South Wales
199.21
53.93
116.32
Victoria
73.63
62.94
94.41
Queensland
253.79
70.85
153.35
South Australia
163.40
43.57
150.69
Western Australia
88.65
62.86
75.76
Tasmania
151.89
112.54
213.77
Northern Territory
524.04
127.04
666.96
These data are displayed in Figure II.2
— 41 —
Consultation rate (per 100,000 individuals
annually)
800
Malignant
Other Benign
Naevus/Mole
700
600
500
400
300
200
100
0
Tas
Vic
SA
NSW
WA
QLD
NT
ACT
States and Territories
Figure II.2 Rate of consultations during which three groups of skin neoplasms were
managed, per 100 000 people annually from AMTS data, by state and
territory
Analysis by state, age-standardised to the estimated 1990 Australian population[121],
showed a trend for malignant skin tumours to be managed at a greater rate by general
practitioners in Northern (Queensland and the Northern Territory) than intermediate
states (New South Wales, Australian Capital Territory and Western Australia), which in
turn reported greater rates than Southern states (Victoria and Tasmania), (Table II.8).
— 42 —
Table II.8
Rates of consultation for skin tumours by states and territories, (crude, and ageadjusted as at 30 June 1990 to the Australian population) from AMTS data
Number of consultations per 100 000
people annually
Overall rate – unadjusted for
differences in state population
'Other
Benign'
'Naevus /
Mole'
'Malignant'
Northern (Queensland + Northern
0.74
1.81
2.68
0.56
1.08
1.75
0.62
1.16
1.00
0.74
1.76
2.78
0.61
1.20
1.76
0.61
1.15
0.96
Territory)
Central (New South Wales +
Western Australia + Australian
Capital Territory)
Southern (Victoria + Tasmania +
South Australia)
Overall rate (age standardised by
state)
Northern (Queensland + Northern
Territory)
Central (New South Wales +
Western Australia + Australian
Capital Territory)
Southern (Victoria + Tasmania +
South Australia)
A discussion, interpretation and summary of the AMTS data is delayed until data from
another source, the Australian Sentinel Practice Research Network (ASPReN), is presented.
This follows.
II.C
Australian Sentinel Practice Research Network (ASPReN)
Introduction to the ASPReN method
An opportunity to obtain more data in this area came from another source. The Royal
Australian College of General Practitioners (RACGP) runs a network of sentinel practitioners.
This is a group of GPs recruited to collect data about certain nominated conditions they
— 43 —
encounter in their practices. They were formed out of several separate sentinel practice
networks running in Australia (one of which I was responsible for in Queensland). GPs were
recruited from advertisements and also personal approach to individuals to participate. The
conditions nominated were decided by a committee (on which I serve), during meetings of
which different proposals are submitted. During one of these meetings I proposed that the
condition 'naevus' should be included.
The method of collecting data is different from that used in the AMTS. Instead of the GPs
describing every condition and reason for encounter for a relatively brief time-period, in the
Australian Sentinel Practice Research Network ('ASPReN') relatively few conditions
(typically 10 –12) are nominated, and the GPs record the number encountered together with
the age and sex of the patient over a longer time period.[122] The different data source might
allow testing of the validity of the data collected by means of the AMTS. Moreover because
the data are collected over a longer time interval, it is possible to determine the secular
changes in addition.
This part of the study was undertaken in collaboration with Dr Kevin Balanda, a statistician
with a particular interest in skin cancer.
II.C 1. Source of the ASPReN data
The data came from the ASPReN between February 1991 and March 1993. The marker
condition of ‘naevus’ was defined as
“(a) A consultation at which a lesion with the characteristic clinical
appearance of naevus is discussed, or (b) Histological confirmation of
clinical diagnosis of naevus”.
Sentinel practitioners recorded the patient’s age and sex for each consultation in which they
managed a naevus. In addition, they recorded the total number of consultations they
conducted during the monitoring periods, although this was without a breakdown of the
patient’s age or sex.
The Health Insurance Commission (HIC) was asked to provide details about the total number
of GP consultations conducted by all general practitioners in Australia during the monitoring
period, broken down by sex, age, state and month.
Data were also obtained from the Australian Bureau of Statistics (ABS) to obtain the
population census.
— 44 —
II.C 2.
ASPReN analyses undertaken
The aim was to derive population rates of consultations in which a naevus was managed
(amongst a particular age-sex group in a specific state during a particular month). First we
assumed that the age-sex distribution of the patients visiting sentinel doctors in a particular
state during a particular month matched that of all general practitioners in that state during
that month. Then the total number of naevus consultations conducted by all general
practitioners (amongst a particular age-sex group in a particular state during any particular
month) was estimated by applying the observed rates (per GP consultation) to the total
number of consultations for all GPs. These counts were then divided by the estimated resident
populations provided by the ABS. Overall rates (ie by sex only, age only, state only and
season only, were obtained similarly by first aggregating estimated total counts.
This approach was employed to estimate rates of consultations in which naevi were managed
(per 1000 persons annually) for each sex, age-group, state, month, season and year. The
construction of 95% confidence intervals (CI) was based on the assumption that the
distribution of naevus consultations amongst all consultations arose from a Poisson process.
Normal approximation to the Poisson was assumed. The analysis does not take into account
clustering of patients by GPs.
II.C 3. ASPReN results
Two hundred and twenty three sentinel GPs, each recording for an average of 26.1 weeks,
reported a total of 749,171 consultations between February 1991 and March 1993 from all
states in Australia. Of these 9,729 were recorded as having involved management of the
diagnostic label of ‘naevus’, a rate of 13.0 ‘naevus-consultations’ for every 1000
consultations.
a) Effect of age and sex on consulting rate (ASPReN data)
There was a difference between the calculated naevus consultation rates between the sexes of
11.3 per 1000 individuals annually (95% CI 11.0 - 11.6) for males and 17.0 (95% CI 16.6 17.5) for females.
There were striking differences between the rates of different age groups, from a maximum in
the 15-44 age group of 21.8 (95% CI 21.8 - 22.4) compared to 6.3 (95% CI 5.0 - 7.5) for the
0 - 4 age group, and of 6.7 (95% CI 6.3 - 7.1) for the 5 - 14 age group, and of 16.0 (95% CI
— 45 —
15.4 - 16.8), 16.1 (95% CI 15.1 - 17.1), and 8.6 (95% CI 7.6 - 9.5) for the 45 - 64, 65 - 74 and
75+ age groups respectively.
Table II.9
Rate for consultations in which naevi were managed by age and sex, per 1000
people annually (95% confidence intervals) calculated from ASPReN data
Annual rates of consultations in which naevi
were managed per 1000 people annually
(95% confidence
intervals)
Age
0-4
6.3
(5.1
, 7.5)
5 -14
6.7
(6.3
, 7.1)
15-44
21.8
(21.2
, 22.4)
45-64
16.1
(15.3
, 16.8)
65-74
16.1
(15.1
, 17.1)
75+
8.6
(7.6
, 9.5)
These data are illustrated in Figure II.3.
Naevus consultation rate (per 1,000
individuals annually)
25
20
15
10
5
0
0-4
5-14
15-44
45-64
65-74
75+
Age groups
Figure II.3
Annual rates of consultations in which naevi were managed, by age, (95%
confidence intervals)
b) Effect of State on consulting rate (ASPReN data)
There was a wide variation across states and territories. The two states with the highest
sunshine (Northern Territory and Queensland) had the lowest and the highest rates of 5.2
(95% CI 4.4 - 5.9), and 17.3 (95% CI 16.8 - 17.9) per 1000 individuals annually respectively.
The most Southerly states (Tasmania, Victoria and South Australia had rates of 8.2 (95% CI
— 46 —
6.76 - 9.6), 12.9 (95% CI 12.1 - 13.7) and 14.4 (95% CI 13.7 - 15.1), while states in
intermediate latitudes, New South Wales and Western Australia, had rates of 15.2 (95% CI
14.4 - 15.9) and 8.5 (95% CI 7.8 - 9.2) respectively.
Table II.10
Rate for consultations in which naevi were managed by state, per 1000 people
annually (95% confidence intervals) calculated from ASPReN data
Rate for consultations in which
95% confidence
naevi were managed per 1000
interval
people annually
State/Territory
NT
11.2
(9.6
, 12.7)
TAS
17.7
(14.6
, 20.8)
WA
18.4
(16.8
, 20.0)
VIC
27.9
(26.3
, 29.6)
SA
31.2
(29.7
, 32.7)
NSW
32.9
(31.3
, 34.5)
QLD
37.6
(36.5
, 38.7)
Naevus consultation rate (per 1,000
individuals annually)
These data are displayed in Figure II.4.
40
35
30
25
20
15
10
5
0
TAS
VIC
SA
NSW
WA
QLD
NT
States and Territories
Figure II.4 Rates of consultations in which naevi were managed by state per 1000 people
annually (95% confidence intervals) calculated from ASPReN data
— 47 —
c) Secular changes of the ASPReN data
The secular changes indicated a seasonal variation, with rates highest in the hot months (of
about 15 consultations per 1000 individuals annually) and lowest in the cooler months (about
13 for the two cooler seasons sampled).
25
By month
20
15
10
5
0
25
By season
Summer
Summer
20
15
10
5
Winter
Winter
Feb-93
Dec-92
Oct-92
Aug-92
Jun-92
Apr-92
Feb-92
Dec-91
Oct-91
Aug-91
Jun-91
Apr-91
Feb-91
0
Figure II.5 Secular changes in rates of consultations in which a naevus was managed, by
season and month, (95% confidence intervals) from ASPReN data
Looking at the same data by months, January 1992 and January 1993 had rates of 18.0 and
19.2 (95% CI of 16.7 - 19.4 and 17.5 - 20.9) respectively, while there were lows in April 1991
and June 1992 of 12.5 and10.1 (95% CI of 11.0 - 13.9 and 8.4 - 11.6) respectively.
— 48 —
II.D
Discussion
II.D 1. methodological problems
a) Clustering of patients about GP recorders
The lack of adjustment for clustering is based on an assumption that patients are not clustered
in a systematic way about GPs. There is no evidence on which to decide whether this is a
justifiable assumption or not. It is possible that some GPs were more likely to attract patients
of a certain kind (say with greater numbers of, or anxieties about, naevi), and that these GPs
were more or less likely to participate in data collection studies of this sort. However any
adjustment for clustering, if it exists, would have to made on the basis of guesswork because
we have no access to data that would allow such estimates to be made.
b) Assumptions allowing the estimates of the 95% confidence intervals
The construction of 95% confidence intervals (CI) was based on the assumption that the
distribution of naevus consultations amongst all consultations arose from a Poisson process.
Normal approximation to the Poisson was assumed. It is possible that the 95% confidence
intervals are not accurate because the assumption does not hold true.
c) Response bias
The modest response rate of GPs responding to the request to supply data for the AMTS might
mean that there is a bias towards those sorts of GPs who respond to calls for providing their
time without payment for providing data for which there is no obvious benefit. Perhaps these
doctors behave differently from others who do not participate. For example they may work
harder. This would provide a higher overall rate of encounter for the three diagnoses which
would be anomalous.
The same problem also exists for the GPs who were involved in the ASPReN: since they were
recruitment by invitation, personal approach and in response to advertisements in Royal
Australian College of General Practitioners' publications, we cannot estimate
representativeness except by such crude measures as demographics. In the absence of such
analyses the representativeness remains unclear.
A study in Sydney found that the morbidity presenting to GPs is representative of that that can
be obtained from community morbidity studies, suggesting that collecting morbidity data from
— 49 —
GPs does not introduce bias in the morbidity patterns.[123] Moreover comparative analyses of
GPs’ diagnostic categories are less likely to be subject to any systematic errors.[124]
d)
Reporting biases relating to unreliable and invalid use of the reporting terms.
The use of the terms 'benign skin tumour, 'naevus/mole', malignant skin tumour' (in the
AMTS) and 'naevus' (in the ASPReN) are inexact. They may mean different things to
different doctors, which will cause unreliability (the results might not be reproducible) as well
as lack of validity (the results might not return what the researchers intended). The more
specific definition of the term 'naevus' in the ASPReN might improve its validity.
The diagnosis of skin malignancy in community settings is known to be difficult: 14
dermatologists working in a clinical setting of low skin cancer prevalence (more similar to
general rather than specialist practice) had diagnostic difficulties with NMSC.[106] Reasons
are not difficult to postulate. Provisional (working) diagnoses should be higher than the real
incidence (the preference being to err on the side of not missing a malignant lesion). In
community (non-referred) settings the smaller concentration of malignant lesions means that
the ratio of benign to malignant is more unequal than in referral clinics. The same percentage
misclassification will result in a higher absolute number of lesions where the ratio of
malignant lesions is smaller.
The method of data collecting did not allow general practitioners in either study to return to
correct previous provisional diagnoses in the light of pathology reports. They must be
regarded as provisional diagnoses only in many instances. These data are a better reflection of
the load represented by skin neoplasms on the work of general practitioners than as true
incidence of skin cancer.
To test validity would have required intrusive methods such as audio- or video-taping the
consultations. This would have been difficult in the ASPReN because it would have required
recording the contents of 98.7% (749 171/9 729) of consultations with no naevi recorded to
test the false negative rate, and a similar rate presumably in the AMTS. The issue of logistics
would be an additional problem. Moreover there remains a problem of the Hawthorne effect,
which describes the influence of observation on behaviour.[125] In this case the effect of the
recording tape might have altered GP recorder behaviour in a way so that they either recorded
consultations in which naevi were managed more or less frequently. It would similarly be
impossible to separate out the effect of the Hawthorne effect of the recording form from that
of audio- or video-recording.
We can therefore only speculate on the possible errors that might have arisen from this
method.
— 50 —
Internal validity checks from comparing the AMTS with the ASPReN
The two methods of collecting data are different from each other. The differences are
summarised in Table II.11.
Table II.11 Comparison of the methodologies of AMTS and ASPReN
Recruitment of GPs
AMTS
ASPReN
Random sample:
Idiosyncratic (personal
denominator available
invitation, response to
advertisement)
Definition of recording
As recorded by GPs, and
Specific definition of a small
items
interpreted by coders
number of conditions
Focus on items of
None: all conditions
Specific to items of interest
interest
recorded
The internal validity of the relative diagnostic rates can be assessed by comparing the results
from those parts of the two studies in which comparable forms of data were collected. This
relates to the 'naevus/mole' item of the AMTS and the 'naevus' defined above for the ASPReN.
The overall rates were different:Table II.12
Calculated numbers of general practice encounters for ‘naevus/mole' (AMTS)
and 'naevus' (ASPReN) per 1000 people annually in Australia by sex
Study
male
female
AMTS
18.7
26.3
ASPReN
11.3
17.0
Although the overall rates are in the same order, and with study differences in the same
direction and magnitude, the ASPReN estimates are 60% (male) and 64% (female) of the
AMTS estimates.
Checking the validity by comparing the AMTS and the ASPReN data with external sources
These data confirm higher rates of skin malignancies from Northern latitudes—where
incidences of skin cancer are highest.[126, 127] The finding that more skin cancer was
— 51 —
reported from older patients is in accordance with previous studies.[128] [8] Naevi/moles
were more frequently reported among young adults, particularly women, which is congruent
with patterns of skin melanocytic lesions sent for pathology.[96]
Clinical significance of the findings
These data emphasise the enormous clinical load borne by general practitioners with respect to
skin tumours. As a percentage of the general practice workload, 1.5% may not appear to be
large at first. However it must be remembered that the range of clinical conditions managed
by GPs is very wide, and no one condition commands a very high proportion of the total. For
comparison, the clusters of conditions causing 'diarrhoea' compromises only 1.1%; upper
respiratory tract infection 1.2% and ear pain 1.5% of all reasons for encounter.[11] Since the
workload of these conditions is estimated in the same way, despite the caveats outlined above,
these figures bear accurate comparison with other data.
The observation that skin cancer is more often managed together with other problems than
most other conditions in general practice requires exploration. Perhaps because these three
markers of skin neoplasms represent a collection of usually slowly developing conditions on
the surface, patients more often perceive them as more' trivial', or think that their GP might.
Either of these developments will encourage patients to bring their skin neoplasm with other
conditions. In an exaggerated form the patient brings something unquestionably serious (the
'ticket') to the doctor to enable something perceived as being of doubtful seriousness by the
doctor (but of real concern to the patient). This phenomenon has been well described, and is
called 'ticket of entry'.[129, 130]
More aggressive surgical approaches were used among cancers than naevi/moles and benign
skin tumours as expected. GPs usually appear to manage these cancers without referral. When
a referral was made, surgeons were more commonly used as referral destinations than
dermatologists, perhaps because help is more often required for difficult excisions than for
diagnosis. However, caution must be observed in the interpretation of the data with respect to
referrals: there was no linking of problems and referrals. Thus we cannot infer that the
different rates of referral for those consultations with different types of skin neoplasm were
associated with those differences, and not a confounding factor.
The seasonal variation suggests that more naevi are managed during the hotter months in
Australia. Possible explanations are that patients, or their doctors, are more aware of skin
lesions as the seasons become warm enough to encourage cooler clothes that expose more
— 52 —
skin; because this time coincides with public awareness messages about the dangers of sun
damage; and that increased sunlight induces changes in naevi[131] that create concern.
Some differences in geographical distribution are difficult to explain. Western Australia lies
across many latitudes, and the Northern Territory has a population and medical workforce in
many respects different from the rest of Australia. Factors in addition to latitude, as a proxy
measure of sun dosage, are important in determining the rate of consultations for managing
naevi.
One of the more interesting findings is that of the age distribution of the workload. The
patterns are different for 'naevus/mole', 'malignant' and 'benign'. The increase in malignant
skin cancer with age is well described.[12] The more modest increase of 'benign' skin
neoplasms with age is unremarkable. However the pattern of 'naevus/mole' is more puzzling.
Naevi/moles were more frequently reported in the young adult age groups, particularly
women. Melanoma incidence increases with age in a linear fashion.[17] One would expect the
management of naevi to roughly mirror the age distribution of melanoma. There are several
possible explanations for dissonance between these two age distributions: changes in naevi in
females are more common in young adulthood[132]; women may use specific kinds of
clothing which are more prone to tactile irritation to naevi (for example brassiere straps);
women may be relatively more concerned about aspects of naevi such as unsightliness in
addition to their possible malignant potential; women may be less inhibited about bringing
medical concerns to the doctor in general.[133] The observation that fewer old people receive
care for naevi than do young adults may be partly explained by the falling prevalence of naevi
with age after the third decade[134], and the greater responsiveness to younger age groups to
preventive health messages.[135] It is consistent with the observation that older men have
melanomas diagnosed at a less favourable prognostic stage.[32] Nevertheless older people are
most at risk of melanoma. The observation raises the possibility that earlier diagnosis of
melanoma in older patients is possible by drawing the attention of primary care clinicians to
this dissonance. This phenomenon is explored in Chapter III in greater detail when a case
series of melanocytic lesions excised from the skin is examined.
— 53 —
Chapter III
Accuracy of the diagnostic techniques used in clinical practice
Introduction to the problem
In Chapter I a case was made for the problem of separating banal naevi from melanomas to be
of greatest clinical diagnostic significance. Although there have been studies which purport to
demonstrate that GPs perform less well than specialists at the detection of melanoma, they can
be criticised on the basis of methodological short-comings. Most of the studies have been
artificial in design, and there are few data to describe the performance of GPs in real practice.
The studies described in Chapter II showed that Australian GPs are busy with the
management of naevi in unexpectedly young people, particularly women, when
the peak activity might be expected to be at the time of most danger from
melanoma. This increases with age and particularly among men.
This is the background to the design of the following line of inquiry in which the
different kinds of melanocytic lesions excised by one pathology company were
studied.
Pathology company analysis of a series of pigmented naevi
Method
This study took place as a medical student project. Three students, Tim Cooney, Ken Cutbush,
and Steven Lawrie approached me asking for a mentor to assist them with a project. They
wanted to undertake 'something in the pathology area'. The project that follows was proposed
in outline and they were assisted with the design, write-up and interpretation, together with a
skin cancer epidemiologist, Dr Adèle Green. They collected the data with the assistance of a
pathologist (Dr Graeme Adkins). Some of the data have been published (See Appendix
1).[136]
The students had 11 weeks during their holiday period to collect data. They negotiated with
the pathology company for them to put aside the histology report of every melanocytic skin
lesion diagnosed in the laboratory. The laboratory, Sullivan, Nicolaides and Partners,
Consulting Pathologists at Taringa, Queensland, provides histological reporting for about one
quarter of the state’s melanomas on the basis of annual totals registered in Queensland.[137]
— 55 —
Each patient’s sex and date of birth was recorded together with the histological diagnosis.
Each diagnosis was categorised into 'benign', 'pre-malignant and pre-invasive', and 'malignant'.
Table III.1 Eligibility of pigmented lesions for inclusion into the study, and their classification
Diagnostic category
'benign'
Abbreviation
B
Included histological diagnoses
Benign naevus; junctional naevus; compound
naevus; blue naevus; halo naevus; Spitz naevus;
congenital naevus; lentigo; freckle
'potentially-
PM
malignant'
Premalignant and pre-invasive lesions (dysplastic
naevus, Hutchinson's melanotic freckle,
melanoma Level I)
'malignant'
M
Excluded lesions
Malignant melanoma (Levels II-IV)
Any non-melanocytic lesion,
eg, haemangioma; pigmented basal cell
carcinoma; pigmented seborrhoeic keratosis
Initial hopes were to obtain the referring clinician's provisional diagnosis, but it was soon
established that only a minority of specimens submitted had such information on the request
form. Usually even the site of the excision was missing. It was beyond the capacity of this
study to interrogate referring clinicians.
Differences between the distributions of benign, pre-malignant and pre-invasive, and
malignant lesions (defined in Table III.1) among patient groups were tested for significance
using the chi-square test after adjusting for age and sex, and confidence intervals.
Results
Complete information was available for 99% of the total of 1 896 reports of excised
melanocytic lesions.
— 56 —
Table III.2
Melanocytic lesions from the pathology company of the diagnostic categories
by age and sex
Diagnostic group (n)*
age
0-9
10 - 19
20 - 29
30 - 39
40 - 59
60+
sex
B
PM
M
total
Male
17
0
0
17
Female
13
0
0
13
Male
207
1
4
212
Female
183
5
1
189
Male
175
8
4
187
Female
303
5
1
309
Male
133
5
3
141
Female
269
9
2
280
Male
118
22
15
155
Female
210
18
13
241
Male
35
12
11
58
Female
62
10
8
80
685
48
37
770
total
Male
total
Female
1040
47
25
1112
total
both sexes
1725
95
62
1882
*See definitions in Table III.1 above
Most lesions, (1499, 78%), were excised from patients under the age of 40 years. Potentially
malignant, pre-malignant and malignant lesions together comprised 8% of all melanocytic
lesions. The proportion increased markedly with age: 4% in the under-40s, 17% in the age
range 40-59, and 30% in those older than 60. This trend was significant (Chi2 = 131.8, p <
0.001; sex adjusted). The proportion was twice that for males (11%), as females, (6%), a
difference that was not significant when adjusted for age (Chi2= 2.45 , p = 0.118).
The trends for invasive melanoma (3% of the total) were similar. The percentage of invasive
melanoma rose from only 1% of the lesions submitted from patients younger than 40; to 7%
aged 40-59 years; and 14% in those aged 60 and older. It was 4% for males compared to 2%
for females.
— 57 —
Table III.3
Melanomas (invasive and non-invasive) by age and sex (these belong to both
PM and M categories)
Male
Female
0-9
0
0
10 - 19
0
3
20 - 29
6
2
30 - 39
6
4
40 - 59
24
13
60+
40
23
These data are displayed in Figure III.1.
Male
Female
40
300
200
20
100
0 -9
10-19
20-29
30-39
40-59
60 +
Age groups
Figure III.1
Numbers of melanocytic excisions, and percentage malignant, by age and
sex, 95% confidence intervals
A check of the representativeness of the 11 week period was undertaken by comparing its rate
of histologically confirmed melanomas with the annual total: it was not significantly different
(p=0.25).
— 58 —
Discussion
This study appears to confirm a dissonance between the age and sex of the greatest activity of
excision of melanocytic naevi (young adults, particularly males) and the people at most risk
for melanoma (the older adults, particularly males).
Methodological problems
There are several potential methodological problems.
Errors in failing to report lesions which should be included, or in including lesions that
should not
Strategies to minimise this were the use of close definitions to clarify the categorisation of
each report. They are defined in Table III.1. Every lesion could be positively categorised.
However some lesions in the State are excised and managed under the public hospital system.
The pathology for these lesions usually is examined by state pathology services. These lesions
may have quite different characteristics. We have no data on the proportion of public hospital
managed lesions treated this way, nor their patterns of the excisions except from a study
which suggests very similar patterns. In that study the total number of lesions excised was
1277 of which 72 were melanomas and 14 dysplastic. Therefore the equivalent proportion of
malignant and potentially malignant lesions in comparison to our figure of 8% was nearly 7%
in the NSW public hospital and medicine study.[96]
Errors in assigning lesions to correct assignments
If lesions were incorrectly assigned to categories errors will have arisen. Again
the use of strict category definitions will have minimised this source of error.
Bias introduced because the pathology service is not representative of pathology services in
Queensland
If the pathology service is not representative of lesions submitted after excision, then error
will be introduced. It was not possible to estimate this because of the lack of data from other
services. However in Brisbane there are relatively few pathology services. There are only
three large services: one is publicly funded; and two, one of which provided the data, are large
private companies, which dominate pathology service available. There is no widely accepted
sub-specialisation into skin pathology such as occurs in some other capital cities.
— 59 —
There is evidence that naevus melanocyte activity is greater during sunny seasons of the
year.[131, 138] Moreover a seasonal effect has been described in Chapter II Section B in the
consultation rate for naevi. Therefore it was important to check that the sample of the lesions
removed were not taken during a particularly busy or quiet time. An estimate of the
representativeness of the 11 weeks time period of the collection period suggests that it was
representative of the year.
Pigmented lesions other than melanocytic lesions had not been evaluated
The principal research question addresses patterns of melanoma excision and
other pigmented lesions. These data only relate to melanocytic lesions. There are
other lesions that might have been included, including BCCs and seborrhoeic
keratoses, which are known to provide diagnostic confusion with melanomas.[28,
139, 140]
This deficiency was accepted to allow a strict entry into the trial to minimise the
inclusion of lesions that might have been less likely to be of concern for
melanoma, and more likely to be removed because they were causing symptoms
such as pruritis or unsightliness. Moreover the pigmentation of some lesions that
are not melanocytic is difficult to establish from the pathological specimen, even
histologically. This would have meant that there would have been uncertainty and
an increased subjectiveness about which lesions to include or exclude. The
inclusion criteria adopted for this study allowed for clear unequivocal decisions to
be made.
Other reasons than to exclude malignancy may have been responsible for the excision
Young women, for example, may be more likely to have naevi removed for cosmetic reasons
than old men. Such an effect would tend to bias the results in over-representing young
women. This effect on the final results cannot be estimated without data on the reasons
patients have pigmented skin lesions excised.
Other methods of managing the lesions are not estimated – under-reporting bias
Pigmented lesions may be managed in two ways: by conservative means, principally
observation; or destructive, presumed to be by excision. Firstly no data are available on which
to make this presumption. Secondly there were no data in the literature at the time of
designing the study on which to assume that lesions excised are submitted for histology,
where they could enter the study. Although the textbook advice for managing doubtful lesions
is to observe them, or excise those that are suspicious[111], it is not certain that all clinicians
follow such orthodoxy.
— 60 —
However some data are available from Chapter II. The ATMS data suggests that few naevi
were destroyed by diathermy or cryotherapy (1% and 2% respectively) compared even with
malignant lesions (6% and 20% respectively). Perhaps clinicians are aware of the dangers in
missing a melanoma. Nevertheless Table II.5 indicates 18% of lesions are treated by other
forms of management, including other less commonly employed destructive methods such as
chemical cautery, as well as incisional biopsy, observation, and a variety of wound care
activities.
Ability to generalise the findings
The types of clinicians (that is, different category of GP, or different types of specialist)
submitting specimens to the laboratory could not be identified from the data available. In part
this was to protect the identity of the clinicians (whose advance consent to be studied
individually was impossible to obtain). Therefore these findings cannot be extrapolated to
general practice. This is clearly an area for which more data would be useful.
Data were only collected from South East Queensland. Therefore assumptions about the
uniformity of conditions between this area and other parts of Australia have to be made in
order to generalise the results.
External validation of the findings
A comparison has already been drawn with the NSW public hospital and medical service in a)
above.[96] This provides external validation of the overall results.
The percentages of patients with melanomas referred to dermatologists by GPs concerned
about melanoma differ between countries (where GPs themselves take on excision less
readily): 0.2% in Holland; 0.4% in the USA; and 5% in the UK.[90] Our figure is in the same
order as the UK figure.
Clinical significance of the findings
Proportion of lesions that were malignant
One important finding is that the proportion of malignant lesions excised in clinical practice in
South East Queensland is very low in relation to the total. We cannot be sure what reasons
induce these excisions, but if the majority of excisions is to exclude malignancy then there are
a lot of 'unnecessary' excisions. That is, for every melanoma excised, more than 12
melanocytic lesions are removed. Such a response for another area of difficult clinical
practice would be unacceptable. For example the management of acute appendicitis has some
parallels. Although it is an acute illness (and melanoma is not), it too is a potentially lethal
— 61 —
illness which can be difficult to diagnose, but whose delayed diagnosis can be disastrous. As a
consequence there is a tradition of removing more appendices than are infected. Senior
clinicians achieve a 92% accuracy for acute appendicitis,[141] considerably better than the 8%
clinicians achieve with naevi.
Yet the clinical parallels are different. Benign naevi are very common. The mean number on
Caucasians aged 20-29 lies between 15 and 40.[134] The annual gross rate of melanoma for
the same age group in Queensland is less than 0.04% (40:100,000).[128] If there is a mean
lead time of about one year before action is taken about melanoma[102], the chance of any
unselected naevus being malignant would be less than about 0.002%. This is much less than
the equivalent 3% in this study, and 5.6% in the NSW study[96], suggesting that patients and
clinicians are quite discriminating in their ability to identify lesions that require removal.
Distribution of the numbers excised with age and sex
The difference in rates among the subgroups is revealing. The incidence of melanoma is more
common in males, and increases with age.[128] The percentage of malignant-to-benign
lesions would remain roughly constant with age and sex if the rate of excisions varied
similarly. However these data suggest that it does not: it is very low among the young, and
females, among whom the incidence of melanomas is low. Reasons other than to exclude
malignancy (for example, cosmetic reasons), may have contributed to these differences a little.
However these results may suggest a lack of specificity in the clinical diagnosis of melanoma
among myriad melanocytic naevi among the young and among females.
Pressure from patients to have clinicians remove their lesions may complicate excision
patterns, particularly in this study’s fee-for-service setting. However these results are
consistent with those from a study based on the New South Wales public hospital and medical
service where questions of fee-for-service did not arise.[96]
What percentage of naevi excised should be malignant? To answer this, it is instructive to
compare the percentages of patients that are found to have melanomas after referral to
dermatologists by GPs with that concern. The rates in countries where GPs themselves take on
excision less readily than in Australia are: 0.2% in Holland; 0.4% in the USA; and 5% in the
UK.[90] The data from this current study have an action plan that is nearer to the UK data.
Otherwise there is little in the literature to guide us in the formulation of a set of standards.
The data derived from this study need information on why patients have naevi removed from
the skin, as well what pressure may exist from the patient on the clinician to allow better
interpretation. This is the subject material of the next chapter, which describes a study that
has a descriptive arm addressing both these factors.
— 62 —
— 63 —
Chapter IV
Further studies into the management of naevi in primary care. The naevus management
study
A Introduction to the methods
Chapter II described how GPs had a large component of their workload devoted to managing
skin cancer in different forms. Managing skin naevi formed a large workload also, twice all
other benign skin lesions, and more than half of all malignant skin lesions. Speculation on the
reasons for this include concern for diagnostic confusion with melanoma. More information
on this would be welcome.
Chapter II also described referrals to specialist care (comprised of either private or public
hospital management). Only a minority of lesions were referred: 22% of malignant lesions;
15% of naevi and 9% of benign lesions. There is little information on other referral processes
of pigmented lesions within the medical profession: possibly GPs refer to other GPs in their
practice – in other words there may be a degree of specialisation within general practice into
those who tend to undertake minor surgery and those who do not, perhaps out of differences
in skill and preference.
Information on the reasons for the very high naevus/malignant and potentially malignant ratio
encountered in the study on melanocytic skin lesions submitted to a pathology service in
Chapter III would be welcome. Anecdotally GPs report that they feel themselves to be under
pressure to excise a lesion when there is any doubt about malignancy. Chapter IV contains
attempts to quantify this 'patient pressure' on clinicians.
Chapter IV also involves an intervention study to try and improve the diagnostic ability of
primary care clinicians with respect to melanocytic lesions.
All these aims were incorporated into a single study in central Queensland.
B The Naevus Management Study
In 1991 The University of Queensland Mayne Bequest Fund and the Queensland Cancer Fund
funded a study into the primary care management of naevi in central Queensland. The chief
investigators were the candidate and Dr Adèle Green.
— 65 —
Subsequently Diana Battistutta
provided statistical advice and joined the team as Chief investigator for some aspects of the
study. Vic Siskind also provided statistical advice.
One component was a descriptive study into the management of pigmented melanocytic skin
naevi in a community. It was designed to answer several questions that emerge from the work
conducted above. The main question were as follows:•
What are the reasons for excising skin naevi?
•
Do GPs usually manage skin naevi that are suspicious on their own without referral?
•
What are the pressures to which clinicians feel subject in excising skin lesions?
In addition we had the opportunity to pose other questions which yet remain unanswered:
•
How much normal tissue do clinicians excise from around suspicious naevi?
This question arises out of a controversy about what is a safe amount of normal tissue to leave
around a melanoma. There is very little information about the margins of normal tissue around
lesions excised under suspicion of being melanomas.
The other component was an intervention trial. It follows from suggestions that GPs, and other
clinicians involved in the primary care of managing skin lesions, appear to have problems
managing the diagnosis of pigmented skin naevi that come from the work outlined in Chapter
I and from the high ratios of benign to total melanocytic lesions excised described in Chapter
III. The main area of interest for this component of the study was to explore to what extent
improving the ability of the clinician to know if a suspicious skin lesion had changed with
time increased clinical accuracy.
The estimate of clinical accuracy is a difficult construct. A proxy for this was the ratio of
melanocytic skin lesions that were neither malignant nor potentially malignant compared to
the total. This is the same outcome measure used in the study of melanocytic lesions
submitted to one pathology service described in Chapter III. In an ideal world the ratio
theoretically would be zero (that is there would be no lesions out of any series removed under
suspicion of malignancy that were not malignant or potentially malignant). If clinicians had
no clinical ability (that is were unable to discriminate between lesions that should be removed
and those that should not) the ratio would be the same as that of lesions among people in the
community.
The challenge facing the study investigators was to demonstrate whether the ratio had
changed in the right direction, and by how much. The ideal design for many intervention trials
— 66 —
is a blinded, randomised controlled design, with an adequate sample size in relation to the
intervention effect to be able to rely on any difference being unlikely to be a consequence of
chance alone. However such a design was not possible here: it would have required the
recruitment of individual practices (or alternatively, multiple communities) to be randomised
to intervention or control. The measurement of the outcomes would have required the sorting
of individual patients into those whose clinicians were randomised to control or intervention.
This would have been difficult: patients might have consulted more than one doctor, including
ones from both intervention and control randomisation. Moreover there might have been a
contamination effect if the units of randomisation had been small. Contamination refers to the
influence of the intervention on the control group's behaviour. In this case the fact that there
were doctors with access to cameras may have influenced both the doctors randomised to
control (to obtain cameras too) and their patients (to consult doctors whom they had heard had
cameras available). The effect of such 'contamination' of controls with an intervention results
in an apparent diminution of the intervention effect by narrowing the difference between the
control and intervention measurements.
A simple 'before-after' intervention trial design could have answered some of these
difficulties. In such a design the change of the ratio from before and after the introduction of
the intervention is measured. The problem of contamination would no longer be a problem.
However such a design is weak because one has to attribute the cause of the change to the
single intervention employed. Other causes for any differences between the outcome for the
control and intervention could be postulated. These would include general influences (for
example national phenomena on the clinical behaviour of GPs), and local influences as well
(for example, a well publicised case of melanoma in the local community might influence the
ratio). As a consequence there may be difficulty attributing the change in outcome to the
intervention.
An alternative design is a mixture of both randomised controlled and before-intervention trial.
It consists of randomising one city to the intervention and using another as a control. Both
before-intervention and after-intervention measures are taken, and differences between the
individual cities are recorded both before and after introduction of the intervention in the
intervention city. Comparisons can then be made between the differences of the before and
after measures of the intervention and control cities. The intervention is relatively insulated
from the control because the cities were 400Km apart. The presence of a control city reduces
the likelihood that any differences in the intervention was a result of a national change in the
behaviour of GPs in relation to managing naevi. However it will not account for differences
arising from the possibility of local changes in the intervention city alone.
On this basis we selected this method of evaluating the intervention.
— 67 —
C Pilot testing
A pilot test was undertaken among general practitioners in Ipswich, west of Brisbane and
quite outside the proposed study area. The time period started at the end of February 1991 and
finished six weeks later. Eight GPs in two general practices and two pathology services
serving the community of Ipswich were approached.
Pathology recruitment
One pathology service had reservations about participating. A pathologist for that service was
approached several times in an attempt to understand the difficulties. The issues were not
completely clear. Some of the reservations may have related to perceived difficulties in
organising the logistics of providing extra pathology reports. Others may have related to a
perception that supplying the data might upset the GPs who ordered the pathology, and
therefore adversely affect the referral rate, (this was a private pathology company). The fact
that the GPs had not yet been recruited appeared to increase his unease. Our proposal to get
permission from the company in principal, and armed with this, collect permission from the
GPs individually, appeared to provide little relief of the reservations. Other factors might have
been ethical (collecting data about patients without their permission). The pathologist never
actually denied permission: he simply failed to reply to recruitment calls after saying he would
think about it and discuss the matter with the company's partners. It became clear that
collecting the information from the pathology companies might be difficult. The other
pathology company was cooperative, and there were no difficulties.
General practitioner recruitment
All but one of the eight GP agreed to enter the study. The one who did not consent was
difficult to evaluate. Several conversations were engaged with him in person and by telephone
in an attempt to understand the problem. He was reserved and unforthcoming about his
concerns. He was certainly alert to the fact that one of the pathology companies had not given
permission ('yet', at that stage). Perhaps he was sensitive to implied criticism that primary care
skin naevus management was sub-optimal, and that his own management pattern would be
available to university academics for their scrutiny, (despite reassurances that data would be
analysed in aggregate only, and that strict confidentiality rules would be in operation).
Another GP (who did consent, however) was explicitly sensitive to the implied criticism that
care might be sub-optimal, and she spent time articulating her expertise in the area of
melanoma and naevus management.
— 68 —
Conduct of the pilot test
Thereafter the collection of the data was straightforward. After six weeks several dozen
specimen results were collected, and data entered into a computer spreadsheet. The pilot test
was stopped, and the participants thanked.
Conclusions of the pilot test were that:-
Recruitment of pathology companies was critical, and a larger component of recruitment time
should be spent on ensuring that there were no misunderstandings of our intent. Recruitment
of the primary care doctors was no less critical. Again it was important to try and re-frame the
recruitment message as something that implied no criticism. Emphasising the difficulties of
the management process was the main direction that was thought to help doctors realise this
was not an exercise of criticism. This led to the development of an algorithm to help explain
the diagnostic dilemma for clinicians which was used in recruiting clinicians for the
intervention.
Recording of data in a computer database (rather than a spreadsheet) might automate the
generation of questionnaires and simplify the management of the data.
D Method
The two components of this study allowed each to be run as if separate studies. Each was
conducted in a separate city. One addressed the descriptive elements of the aims outlined
above. The data were collected in exactly the same manner as in the other city, and indeed this
component of the study served the dual purpose of an independent descriptive study and also
acting as a control city in a randomised trial.
In the second city the other component of the study was an intervention trial in which the
primary care doctors were visited and provided with an algorithm to present the problem of
the difficulty of diagnosis for primary care clinicians, and a camera.
D.1
Choice of the cities
Two provincial cities in central Queensland were selected on the basis of their similarity: both
are relatively isolated tropical cities near the coast with populations of around 55,000 and
65,000 people working in industries with substantial agricultural and tourist components. The
cities are 400Km apart, sufficiently far that an intervention in one city was unlikely to affect
clinical behaviour in the other. The city to be the subject of the descriptive study was chosen
at random by the spin of a coin. Each city is served by about 50 GPs, with additional junior
hospital doctors who also are involved in primary care.
— 69 —
D.2
Recruitment of pathologists
Only one pathology laboratory provided histology service in the intervention city to both
private and public patients. Agreement was reached satisfactorily.
The two pathology services in the control city (one public and one private) eventually
cooperated. The public pathology service (based in Rockhampton Base Hospital) agreed
without ado. The private pathology company only agreed on the proviso that every doctor
agreed to take part (on an 'all-in-or-none-in' basis). Preliminary contact with the pathologist
and owner of the company had not indicated any such proviso would be imposed. His concern
was not wanting to have a complicated logistic for the management of reports within the
laboratory.
D.3
Recruitment of medical practitioners
Lists were drawn up of every doctor who was a primary care doctor with respect to skin
cancer in each city from a combination of the telephone Yellow Pages, and lists held by the
pathology services in each city. Additional information was obtained from contact doctors in
each city who knew all the other doctors and could provide local information about them.
They were the Area Coordinators in each city for the Royal Australian College of General
Practitioners (RACGP) Family Medicine Programme (FMP) (now called the Training
Program). The list was refined to include only those whose practice included the management
of skin cancer as a primary responsibility (junior hospital doctors, GPs, general or
reconstructive surgeons and one dermatologist). A radius was plotted around the central post
office on a map of the city, and only those doctors with practice addresses within the that
radius were included. Permission from the Base Hospital Superintendent in each city was
obtained so that junior hospital staff would automatically be enrolled as directed by their
employer. This dealt with what would have been a complicated recruitment as junior hospital
doctors left during the year and new doctors took their place.
Every doctor on these lists was now visited by one of us (CDM or AG) or on occasion both,
on a 6-day field trip from 15 to 20 April 1991 to explain their possible role in the study and
invite participation. Doctors were asked to give permission for a copy of the histology report
of every melanocytic skin lesion they excised over the next two years, and they had excised
already in the previous six months, to be sent to us by the relevant pathology service.
Informed consent of the doctors took the form of a signed sheet, copies of which we delivered
to the pathology services.
Because the control city private pathologist had indicated cooperation only if all the primary
care doctors in the control city were recruited, there was very strong pressure to successfully
recruit all the primary care doctors in that city. This was achieved. Consent was obtained from
— 70 —
all 52 medical practitioners (44 general practitioners, seven surgeons and one dermatologist)
approached in the control city. Over the two year intervention period, nine new treating
doctors entered and two left the control city. All new incoming doctors agreed to take part.
However three doctors in the control city had ethical concerns. They were concerned that
release of patient details to study personnel should require patient permission first. This was
despite an NHMRC-constituted Ethics Committee of the University of Queensland granting
the study ethical clearance. We negotiated individual compromise positions as follows:•
One stipulated that only first name, initial of the surname and date of birth could be
released to study personnel;
•
Two doctors did not want any patient details (name, or date of birth except the year of
birth) identified to the study group.
Such a complicated protocol was acceptable to the control city private pathologist, and he
provided consent.
Not all the doctors in the intervention city agreed to take part. Some felt that the intervention
could only detract from good patient care, and declined on this basis to participate. Consent
was obtained from 52 out of 55 medical practitioners (48 out of 51 general practitioners and
all four surgeons) in the intervention city. New doctors coming into the intervention city after
the start of the study were also invited to participate. All agreed to take part except for one
general practitioner.
Pathology laboratories supplied aggregate data regarding the melanocytic lesions excised by
the medical practitioners who did not participate. There were no changes in reporting
procedures of the pathology laboratories during the period of the trial.
Data were collected from every doctor except locum tenens and those occasionally submitted
from doctors also not recruited into the study. For example there was at least one lesion from a
gynaecologist, and one each from a visiting facial surgeon and a visiting reconstructive
surgeon.
D.4
Difficulties with maintaining cooperation with one pathology company
There were three subsequent problems despite consent from the private pathology company in
the control city. Data stopped coming from this laboratory at the start of 1992. The pathologist
had problems organising the logistics of the paperwork. The solution we finally hit upon was
to send Lyn Francey (our research assistant) to spend three days with his laboratory during
which time she was able to arrange the system effectively.
— 71 —
Another crisis occurred in August 1992. Understanding the problem required visiting the
laboratory. The second problem was unrelated to the study: it involved a dispute with the
Health Insurance Commission with which the study investigators were unable to help. The
data did come several months late. We assisted in the backlog by sending a research assistant
(an English elective medical student called Louise Carruthers) to work in the laboratory.
A similar situation occurred again in May 1993. Visits to the pathologist yielded a negotiated
return to the data collection. Once more the cause of these difficulties lay outside the study.
For similar reasons there was a delay in obtaining the pre-prospective six months of data
(16 October 1990 to 16 April 1991). In the end we obtained them at the end of the study
period (in May 1993).
D.5
Melanocytic lesions
The study was limited to melanocytic lesions excised from the skin. The definition for the
lesions to be included was specific and the same definition was used as that in the study in
Chapter III, Table III.1. This had the advantage of being able to decide easily and reliably for
each report:•
Whether the lesion was eligible for inclusion;
•
How it may be classified into one of three groups:1
‘invasive melanoma’ (level II and above);
2
‘potentially malignant’ (either pre-malignant, ie in situ melanoma and lentigo
maligna; or atypical or dysplastic naevi, whose presence may have clinical
significance for future surveillance of a patient for melanoma);
3
‘benign’ ie halo, compound, dermal, intradermal, Spitz, balloon cell, blue, junctional,
combined, or unclassifiable types of naevi, and lentigines.
From 16 April 1991 until 16 April 1993, a copy of the pathology report for each melanocytic
skin lesion that was excised was sent to the study research assistant in weekly batches.
Reports from the previous six months prior to 16 April 1991 were collected in addition. This
was for two reasons: 1) as a baseline to check that excision rates of benign and malignant
melanocytic lesions were comparable between the two cities; and 2) to extend the sample of
some of the descriptive data.
D.6 Data management
A research assistant (Lyn Francey) was employed to enter the details into a computer
relational database for which the chief investigator had written a program. The program
served two functions: it stored the data collected from the report, and also automatically
generated a questionnaire. This meant that the doctor who referred the specimen received a
— 72 —
questionnaire through the post and a pre-paid envelope for returning it. Doctors were asked
the following:•
the reasons for excision;
•
the level of ‘pressure’ (if any) exerted by the patient to have the lesion removed;
•
by whom (if anyone) the patient had been referred. If the patient had been referred, this
information allowed another questionnaire to be sent the referring doctor.
— 73 —
Different forms were used for both components of the study. This was to de-emphasise the
fact that data from the control city were to be used to estimate changes arising from the
intervention. It was hoped this would minimise any Hawthorne effect.[125] Because all the
data relating to two components of the study were handled in one database, it was important to
distinguish between the two: this was achieved by the program which automatically looked up
the doctor and inserted the correct study heading into the questionnaire.
Figure IV.1 An example of the questionnaire sent to the referring doctor for each specimen (in
this case the control city)
— 74 —
The data contained in the questionnaires returned to the University of Queensland Medical
School were also entered into the database. This allowed for the automatic generation of
reminder questionnaires if there was no response from the submitting doctor after a one month
period.
Figure IV.2
The data collected on each specimen (data entry form)
— 75 —
Reports of non-responders were generated from within the computer program. They were
contacted personally by telephoning.
The data were managed for both studies in one relational database program. There was a file
of doctors that was maintained separately, but linked to another file on lesions ('patients').
Each lesion was treated as a separate record and given a separate Study Number (generated
automatically), Figure IV>2. This number was written on every pathology report, so that the
data from different lesions from the same patients were collected and managed separately.
Data on the site of the lesion distinguished melanocytic lesions excised on the same occasion
from the same person.
A data management algorithm was followed in such a way that the collection of information
about referrals of excised lesions, and the reason for the referral, could be tracked back to the
doctor who made the initial referral, Figure IV.3.
Figure IV.3
The management of the data from the descriptive and intervention
components of the Naevus Management Study. 'Doctor 1' = doctor of first
contact; 'Doctor 2' the doctor to whom first referred (if any); 'Doctor 3' =
doctor to whom referred (if any).
— 76 —
The same database was able to generate letters designed to keep the study doctors informed of
progress with the study. These were sent out every six months approximately.
If a doctor did not respond in 4-6 weeks to a questionnaire about a specific excision, a
reminder was sent (Figure IV.3). Those who persisted were sent reminders again, then
telephone calls from Lyn Francey, and finally from chief investigator CDM. Doctors from
both intervention and descriptive arms of the study responded to questionnaires about all
submitted lesions except 35, (the majority from one GP in Mackay).
Rules for exclusion and inclusion of data as special cases emerged were developed, Tables
IV.1 and IV.2.
Table IV.1
Rules generated for exclusion and inclusion of data as special cases emerged
Situation
Example
Decision
Patients from outside the
exclude
district (as determined by
postcode)
Patient living in the city, but
A patient of Rockhampton
treated by a doctor outside the
whose medical father in
15Km zone
Brisbane excised the lesion
Melanocytic lesions not of
Naevus of conjunctiva
exclude
exclude
skin
Specimens send from hospitals
exclude
outside the district
Lesions of several kinds from
Only include the
the same patient
melanocytic ones
Wider excision following a
Specimen includes a scar
melanoma
Exclude, but include if
there is a melanocytic
lesion as well
Rules for the classification of codes for the sites of the body as special cases emerged were
similarly developed.
— 77 —
Table IV.2
Rules developed for the classification of sites from clinical descriptions written
on the form by the submitting doctor.
Descriptions
Classification
Elbow, arm, axilla
'upper arm'
Leg; knee; foot; heel; toe
'lower leg/top of foot'
Leg stump; between toes; instep; side of foot, (foot lesions not
'sole of foot'
otherwise specified)
Leg above knees; hip; groin
'Thigh'
Eyebrow; naso-labial fold; temple; maxilla; orbit; canthus; malar
'Face'
region; mandible; occular angle; ala nasi; orbital; infra-orbital;
parotid; zygoma;
Head
'scalp'
Below ear; cervical area; sub-mandible
'Neck'
Iliac fossa; pubic area; scrotum; vulva; labia; umbilicus; belt line;
'Abdomen'
penis; subcostal; side; waist; pelvis; quadrant; perineum;
quadrant; epigastrium;
Sternal notch; clavicle; costal margin; thorax;
'Chest'
Popliteal fossa;
'Lower leg'
Peri-anal; natal cleft;
'Buttocks'
Outer helix; auricular; pinna;
'Ear'
Iliac crest; renal area; flank; trapezius; scapular; spine; trunk;
'Back'
proximal margin; post waist area; dorsal area; dorsum;
Bra strap; bra line
'unclassifiable'
The rule was a working system based on the best estimate of the clinician's intention. For
example 'labia' could theoretically mean oral or vaginal lips, but in common usage it means
vaginal.
The size of the lesions was recorded. When only one dimension was given, it was recorded as
the diameter.
— 78 —
Figure IV.4
Data entry form used for coding data and entering dimensions
Data entry into the computer and coding of the fields illustrated in Figure IV.4 were enacted at
a later date (this suited the time management of the research assistant, Lynne Francey, who
could undertake this work in quieter times).
The database was programmed to automatically undertake internal checks of validity. For
example some data from each primary form (date of birth, excision date, and the coded result),
and from the questionnaires (whether the doctor was the primary treating doctor; the patient
pressure score; and the reason for excision) were double entered. The program indicated an
alert if there was a mismatch. An external check of validity was set up: date of birth generated
the age, which was checked against that on the pathology form. A 'millennium bug' in the
program was discovered. Two patients were older than 100, and only a two numbered field for
year of birth had been provided, so they registered as being of infant age. These were
corrected manually by selecting out all records of patients apparently younger than 10 (no-one
older than 109 was assumed).
Codes were set up for the fields displayed in Table IV.3. The code allowed only a limited
response for the data – only certain choices being accepted by the program at data entry. This
was effected by the use of limited options in a 'drop-down menu' within the data-base
program.
— 79 —
Table IV.3
Codes used for the data of the Naevus Management Study
Site of excision
1-face
Diagnoses
Ephelis
Reason for
Patient
excision
pressure
Exclude
1 (none)
malignancy
2-scalp
HMF
Discomfort
3-neck
Lentigo
Cosmetic
4-ear
Melanoma -
Other
Indeterminate
5-back
3
Melanoma Lentigo maligna
6-shoulder
2
4
Naevus with
melanoma in situ
5 (patient
pressure
7-chest
Melanoma Nodular
8-abdomen
Superficial
only reason
spreading
for
Melanoma
9-upper arm
Naevus - Halo
excision)
10-forearm/hand Naevus Intradermal
11-thigh
Naevus - Spitz
12-lower leg/top Naevus - balloon
of foot
13-sole of foot
Naevus - blue
14-buttocks
Naevus combined
15-information
Naevus -
not available
compound
16-information
Naevus - dermal
undecipherable
Naevus dysplastic
Naevus intradermal
Naevus junctional
— 80 —
Naevus regenerating
Naevus sebaceous
Naevus - spindle
Naevus unclassified
Missing
D.7 The intervention
The doctors in the intervention city were visited in the same manner as those in the control
city. In addition, during the visit they were invited to engage in discussion about the
management of melanocytic naevi in relation to the use of an algorithm we had developed
from the literature. The algorithm is outlined in Figure IV.5.
— 81 —
Figure IV. 5
The algorithm offered to help clinicians with the management of pigmented
skin naevi at the time of recruitment.
This algorithm was offered as a means of simplifying the complexities to emphasise the group
of lesions for which there might be most difficulty in management. It was not offered as a
formal guideline: the emphasis was that the normal responsibility of care lay with the clinician
as normal.
The algorithm was also accompanied by the provision of the Polaroid camera. A bulk
purchase of cameras was undertaken using funds from the grant. They were instant–
developing colour cameras made by Polaroid with a 'close-up' stand attachment, Figures IV.6
and IV.7.
— 82 —
Figure IV.6
The Polaroid instant developing camera with the 'close-up stand', dissembled
(and pen for scale).
A 'close-up' stand is a plastic enclosure with a set of extra lenses to act as a 'macro' (close-up)
lens, and mirrors designed to redirect the flash towards the closer focal point at the correct
intensity.
Figure IV.7
The Polaroid instant developing camera with the 'close-up stand', assembled
(and pencil for scale).
The enclosure allows the whole camera and close-up stand to be placed as a unit over the
object to be photographed, it is very simple to operate. Very few photographic skills are
required.
— 83 —
The main thrust of the conversations during the recruitment meetings with the different
doctors related to the unnecessary excisions of melanocytic lesions in primary care. This was
portrayed as evidence of the difficulty in managing melanocytic naevi of the skin in general
practice. Lastly, the algorithm with the access to camera was offered as a means by which the
text-book suggested methods of observing doubtful lesions could be implemented. The
majority of doctors thought this a sensible approach, and agreed to take possession of the
camera for the duration of the trial (two years). Questions and discussion were encouraged
during these visits. Most questions centred on the logistics of using the cameras, and replacing
film.
Doctors in the intervention arm of the study were sent a questionnaire about the processes of
using their cameras. This did not include junior hospital staff doctors because
•
junior staff, being transient, would have been difficult to locate (many would have moved
to other places in Australia); and
•
we discovered that only a minority of lesions were excised in the public hospital).
The questionnaire is detailed in Table IV.5:-
— 84 —
Table IV.5 Questionnaire sent to medical clinicians enrolled in the intervention study at its
conclusion.
Question
Q1
Answering options
How many times did you use the camera per
n
week?
Q.2
Where was the camera kept?
(open field)
Q.3
Did you have technical difficulties?
Yes [ ]
No [
]
(Please comment)
Q.4
Where did you store the pictures?
Q.5
•
Patient’s main record
•
Patient’s secondary record
•
Special file
What was the average number of photos per
n
patient per visit?
Q.6
Was there provision for patients to take
B 1.
Never
photos away with them?
B 2.
Half the time
B 3.
Sometimes/occasionally
B 4.
Always
Are photos accurate in respect of:
……
a
size?
Yes [ ]
No [ ]
b
colour overall?
Yes [ ]
No [ ]
c
colour variation?
Yes [ ]
No [ ]
d
characteristics of edges
Yes [
]
No [
]
e
surface features?
Yes [
]
No [
]
Were the photos helpful in documenting
Yes [ ]
No [ ]
No [
Q7
Q8
changes later?
Q9
Was follow-up more accurate?
Yes [
]
]
Q.10
Were photographs reassuring for patients?
Yes [ ]
No [ ]
Q.11
Did you reduce unnecessary excisions?
Yes [ ]
No [ ]
Q.12
Did patients attend for follow-up?
Yes [ ]
No [ ]
D.8 Analyses
The main outcome of interest from the study was the ratio of melanocytic skin lesions that
were neither malignant nor potentially malignant to the total number of melanocytic skin
lesions.
— 85 —
In the descriptive component of the study the ratio was analysed with reference to several
variables, including the diagnosis of the lesion, doctor and patient characteristics.
Margins of excision data
The margin of excision was defined as the difference between the radius of the specimen and
that of the lesion measured in vitro by pathology personnel. In most cases, an average
diameter of the lesion was recorded. The length and breadth of the lesions were recorded in
209 cases consistent with elliptically shaped lesions. However, as the coefficient of
eccentricity was greater than zero for only 44 of these lesions (representing 1.3% of the total
lesions), we assumed that all lesions were approximately circular in area for our calculations
of excision margins; length and breadth were averaged to estimate diameter for the subgroup
of 209. Specimen dimensions were similarly estimated.
Variation in the margin of excision was considered with respect to patient and doctor factors.
These included histological classification of the lesion, sex and age of the patient, the type of
and time since graduation of the primary doctor, size of the doctor’s practice, the number of
referrals for the lesion, reason for the excision, and the degree of perceived patient pressure to
excise.
There was significant skewness in the frequency distribution of the margin of excision, which
was overcome by a logarithmic transformation,
Ln(margin+0.5)
and consequently geometric
means have been reported, with estimated 2.5 and 97.5 percentiles. Analysis of variance
models were used to compare mean margin of excision across subgroups of the above listed
lesion, patient and physician characteristic variables, adjusting for sex and age of the patient,
and controlling for histological subtype. The association of number of referrals and
histological type was considered using a Chi squared contingency table test.
The intervention component
For the intervention component of the study, during the data entry the cities were given a code
number. This allowed the analysis to proceed blind to which city received the intervention.
All data analysis was performed before the city-identifying code was broken. Comparisons
were made between the cities at baseline, and between and within cities post-intervention,
with respect to age, sex, classification of lesion, and anatomical site grouped as head and neck,
trunk, arms, legs, and buttocks. Differences in proportions were analysed univariately by the
— 86 —
chi squared test, and in median age and melanoma thickness by the Wilcoxon two-sample test.
Estimates of the magnitude of the intervention effect were finally adjusted for the potential
confounding effects of sex, age, and site of the lesion using multi-variate logistic regression
analysis. Differences between cities with respect to changes from baseline to afterintervention were examined by fitting an interaction term to these multi-variate models.
— 87 —
E Results of the descriptive component of the study
First the data from the descriptive component of the study are presented.
Table IV.6
The demographic variables of patients from whom specimens were submitted
for histology
Six months prior
Two years of
to prospective
prospective data
data collection
collection
n
Total excised
%
752
n
%
2 468
Total
n
%
3 220
lesions
Sex:male
326
44
1 013
42
1 339
42
female
425
56
1 426
58
1 851
58
< 20
206
28
637
26
843
27
20-29
197
26
694
29
891
28
30-39
162
22
538
22
700
22
> 40
182
24
551
23
733
23
Age years:-
Median Age:-
28
(range)
28
(0,94)
28
(1,87)
(0,94)
Site of lesion:head & neck
170
24
518
22
688
22
trunk
375
52
1 315
56
1 690
55
arms
76
11
240
10
316
10
legs
89
12
270
11
359
12
buttocks
5
1
28
1
33
1
These data suggest that more males than females had lesions excised, and that the majority of
excisions were in patients under the age of 40 years of age. Their median age was only 28.
The majority of lesions were removed from the trunk.
— 88 —
Table IV.7
Histological diagnoses of melanocytic skin lesions excised and submitted for
histology
Histological diagnosis
n
%
Ephelis
6
0.2
16
0.5
140
4.3
83
2.6
2
0.1
Melanoma - Naevus
21
0.7
Melanoma - Nodular
6
0.2
Melanoma – superficial spreading (SSM)
33
1.0
Naevus - Halo
59
1.8
Naevus - Intradermal
2
0.1
Naevus - Spitz
7
0.2
Naevus - balloon
4
0.1
60
1.9
Naevus - combined
9
0.3
Naevus - compound
1384
43.0
875
27.2
37
1.1
Naevus – intradermal
125
3.9
Naevus – junctional
311
9.7
2
0.1
16
0.5
8
0.2
14
0.3
HMF
Lentigo
Melanoma – Indeterminate
Melanoma – Lentigo Maligna
Naevus - blue
Naevus - dermal
Naevus - dysplastic
Naevus – regenerating
Naevus – sebaceous
Naevus – spindle
Naevus - unclassified
3220
Most lesions excised were naevi, particularly compound and dermal. Melanomas constituted
4.6% of the lesions, of which superficial spreading melanomas (SSMs) were the most
commonly classifiable. Freckles were uncommon lesions to be excised, and Hutchinson's
melanotic freckles (HMFs) only 1/2%.
— 89 —
Table IV.8 Histological diagnoses of melanocytic skin lesions excised and submitted for
histology by time collection period, and grouped into major management
categories
Six months before
Two years following
prospective data
prospective data
collection
collection
Total
Total excised lesions
%
752
Total
%
2 468
Averagea
617
Diagnosis
benign naevus
666
89
2 210
90
lentigo
39
5
101
4
dysplastic naevus
10
1
27
1
HMF
3
0
13
1
Melanoma
32
4
113
5
other
2
0
4
0
Total potentially malignant lesionsb
45
153
47
level I
3
30
8
levels II+
28
82
26
unknown level
1
1
-
96.1%
96.6%
(94.8-97.5%)
(95.9-
Total Melanomas
Percentage of lesions that were noninvasivec
(95% confidence interval)
97.3%)
Percentage of lesions neither invasive
nor potentially malignantb, c (95%
94.0%
(92.3-95.7%)
confidence interval)
93.8%
(92.894.8%)
Median Melanoma thickness (mm)
(range in mm)
0.40mm
0.60mm
(0.10-4.20)
(0.2011.00)
Lesions for which there were missing data for a particular variable are excluded.
a
Six-monthly average for direct comparison of counts with baseline phase (expected values
calculated based on the baseline total)
b
Potentially malignant lesions include melanomas, Hutchinson's melanotic freckles and
— 90 —
dysplastic naevi
c
Percentage of the total number of excised lesions.
The great majority of lesion were benign naevi. Only 3.4% were invasive melanomas (level II
or above), and 4.5% were melanomas of any thickness.
The excision of about 94% of lesions would have conferred no direct benefit in terms of
cancer risk to the patient because they were neither malignant nor potentially malignant.
The reasons for undertaking the excision were derived from the questionnaire responses,
Table IV.9. These data come from 2468 specimens collected during the two years of the
prospectively collected data.
Table IV.9 Reasons for excision of 2468 lesions given by the treating clinician
n
%
to exclude malignancy
1871
78
discomfort
237
10
cosmetic
188
8
other
110
5
Reason for excision given
by excising doctor:-
Total
2406
Missing data
62
2.6
The great majority of lesions were excised to exclude malignancy. Of the remaining 22%,
most were excised for discomfort and cosmetic reasons. Dissecting out further the 'other'
reasons category, which made up 5%, is not possible because the appropriate data to allow
this were not collected.
The perceived pressure on clinicians to excise lesions was also derived from the questionnaire
responses, Table IV.10.
— 91 —
Table IV.10 Perceived pressure from patients on the treating clinician
n
%
532
22
2
426
18
3
655
27
4
474
20
314
13
1
'no patient pressure'
1
'patient pressure
only reason for
excision'
2401
Total
67
2.8
Missing data
In only 22% of lesions did the patient exert no pressure on the doctors to excise their lesion,
according to the perception of the treating doctor. Conversely, 13% were excised only because
of perceived pressure on the doctor by the patient. In other words, the decision to excise in
78% of lesions was influenced at least in part by the doctor's perception of the patient's
pressure.
Site of excision data are presented in Table IV.11.
— 92 —
Table IV.11Frequencies of excisions by site of excision
Site of excision
Count
1-face
%
405 12.6
2-scalp
31
1.0
3-neck
209
6.5
43
1.3
4-ear
5-back
1017 31.6
6-shoulder
226
7.0
7-chest
246
7.6
8-abdomen
201
6.2
9-upper arm
220
6.8
96
3.0
11-thigh
164
5.1
12-lower leg/top of foot
188
5.8
7
0.2
14-buttocks
33
1.0
15-information not available
84
2.6
16-information undecipherable
50
1.6
10-forearm/hand
13-sole of foot
Total
3220
The majority of lesions were removed form the back, followed by the face. Similar numbers
were removed from chest, shoulders, neck, abdomen and upper arms. The ear, buttocks and
sole of the foot were least common sites for excision of melanocytic lesions. These sites have
not been corrected for differences in the surface area of the sites.[142]
In order to examine the relationship between different histological types of melanocytic lesion
and the site of excision, the data were cross-tabulated, Table IV.12:-
— 93 —
Ephelis
HMF
Lentigo
Melanoma Indeterminate
Melanoma – lentigo
maligna with
melanoma insitu
Melanoma with
naevus in situ
Melanoma –
Nodular
superficial
Melanoma - SSM
Naevus - Halo
Naevus –
Intradermal
Naevus - Spitz
Naevus - balloon
Naevus - blue
Naevus - combined
Naevus - compound
Naevus - dermal
Naevus – dysplastic
Naevus –
intradermal
Naevus - junctional
Naevus –
regenerating
Naevus – sebaceous
Naevus - spider
Naevus - spindle
Naevus –
unclassified
Total (3220 overall)
5
7
28
6
0 0
0 0
0 14
0 3
0
0
2
1
1
0
0
0
0
0
1
0
0
0
6
1
0
0
0
2
2
0
0
0
0
2
1
0
1
0
0
1 0 0 0
0 0 1 1
8 5 3 2
1 0 1 1
75 12 79 8
197 12 88 21
1 0 1 1
38 2 8 2
6
0
0
0
8
0
1
0
13
3
1
8
0
0
0
0
0
0
0
0
1
0
1
0
0 0 0
3 0 0
22 15 14
26 2 0
16-information
undecipherable
15-information not available
13-sole of foot
14-buttocks
12-lower leg/top of foot
11-thigh
10-forearm/hand
9-upper arm
8-abdomen
7-chest
6-shoulder
5-back
4-ear
3-neck
2-scalp
Cross tabulation of histological diagnosis with site of surgery
Sit
1-face
Table IV.12
0
0
3
3
1
3
11
11
0
0
7
4
0 0 0
1 2 0
4 17 0
6 18 0
0
0
0
0
0
0
2
1
0
0
1
2
0
0
0
0
0
1 0
0
0
0
4
1
0
3
2
0
4 0
0
0
0
1
1
0
0
1
1
0
1 0
0
0
0
7
34
1
4
7
0
0
5
0
0
3
0
3
1
0
6
2
0
2
2
0
4 0
1 0
1 0
0
0
0
1
1
0
1
0
0
1 1 0 0
1 1 0 0
7 1 1 0
4 1 0 0
556 91 123 106
188 60 74 47
15 4 4 2
25 5 8 10
0 0
0 4 0 0 0
0 0
0 0 0 0 0
5 13
2 12 0 0 1
0 0
0 1 0 0 0
98 31 73 59 5 18 36
48 14 32 29 0 8 29
4 0
1 3 0 1 0
9 4
7 3 0 2 2
0
0
0
0
15
28
0
0
118 28 15 26
0 0 0 0
20
1
9 34 27 2
0
0 1 0
3 10
0 0
3
0
0
0
1
2
0
0
0
0
1
1
0
0
0
0
0
0
405 31 209 43 1017 226 246 201 220 96 164 188 7 32 85
50
0
0
2
0
0
0
1
0
1
0
0
0
0
0
1
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
The number of different histological types made the study of this relationship difficult.
Accordingly the histological types were collapsed into the same categories used in the study
— 94 —
of the ratios of different groups of melanocytic lesion. This allowed the ratios of benign to
malignant lesions to be studied, Table IV.13:Table IV.13
Cross tabulation of the summaries of the diagnosis with site of surgery
Site
All
All
All
Total
melanoma potentially benign
s
Ratio
malignant
malignant
and
potentiall
y
malignant
to total
(%)
1-face
11
19
386
405
4.7
2-scalp
0
0
31
31
0.0
3-neck
5
6
203
209
2.9
4-ear
2
3
40
43
7.0
5-back
40
58
959
1017
5.7
6-shoulder
11
15
211
226
6.6
7-chest
1
5
241
246
2.0
8-abdomen
3
5
196
201
2.5
9-upper arm
18
25
195
220
11.4
10-forearm/hand
13
13
83
96
13.5
11-thigh
8
10
154
164
6.1
12-lower leg/top of foot
28
33
155
188
17.6
13-sole of foot
0
0
7
7
0.0
14-buttocks
0
1
31
32
3.1
15-not available
2
2
83
85
2.4
16-indecipherable
3
3
47
50
6.0
145
198
3022
3220
7.9
Overall
Most melanomas were removed from the trunk (total from back, shoulder, chest, abdomen and
buttocks was 55; 37.9%); the legs (28; 19.3%) and the head and neck (18; 12.4%).
The overall distribution was unlikely to be attributable to chance alone (p<0.001). The sites
with the lowest ratio of potentially malignant-to-total melanocytic lesions were the chest,
abdomen and neck. The sites with the highest ratio of potentially malignant-to-total
melanocytic lesions were the lower leg/top of the foot, and all of the upper limb.
— 95 —
Data were collected on the method of excision of the specimen from the pathologist. The data
are presented in Table IV.14:Table IV.14Frequencies of excisions by method of excision
Surgical method
Excision
Count %
2622
81.5
Shave
355
11.0
Other
239
7.4
4
0.1
Uncertain
Total
3220
Excision was the most commonly performed method of removal of lesions submitted for
histology, although shave biopsies accounted for 11%. Again, the data are cross tabulated
with the histological diagnosis, Table VI.15:-
— 96 —
Table IV.15 Cross-tabulation of the histological diagnosis with the form of surgery
Excision Other Shave Uncertain Total
Ephelis
1
0
5
0
6
15
1
0
0
16
105
14
21
0
140
75
7
1
0
83
Melanoma - Lentigo maligna
2
0
0
0
2
Naevus with melanoma in situ
20
1
0
0
21
5
1
0
0
6
Superficial spreading Melanoma
26
6
1
0
33
Naevus - Halo
54
1
4
0
59
Naevus - Intradermal
2
0
0
0
2
Naevus - Spitz
4
3
0
0
7
Naevus - balloon
4
0
0
0
4
49
4
7
0
60
Naevus - combined
8
1
0
0
9
Naevus - compound
1195
86
102
0
1383
591
89
192
1
873
Naevus - dysplastic
25
10
2
0
37
Naevus - intradermal
116
9
0
0
125
Naevus - junctional
287
6
17
0
310
2
0
0
0
2
14
0
2
0
16
8
0
0
0
8
13
0
1
0
14
HMF
Lentigo
Melanoma - Indeterminate
Melanoma - Nodular
Naevus - blue
Naevus - dermal
Naevus - regenerating
Naevus - sebaceous
Naevus - spindle
Naevus - unclassified
Missing
Total
4
2621
239
355
1
3220
These data are rendered easier to examine if the histological categories are collapsed, Table
IV.16:-
— 97 —
Table IV.16 Cross-tabulation of the summary histological diagnosis with the form of
surgery
Histolog All
All
y
potentially
melanomas
All benign
Total
malignant
n
%
n
128
88.3
40
75.5 2453 81.2 2621 81.4
Other
15
10.3
11
20.8
Shave
2
1.4
2
3.8
Uncertai
0
—
0
—
Excision
%
n
213
%
7.0
351 11.6
1
—
n
239
%
7.4
355 11.0
1
—
n
Total
145 100.0
53 100.0 3022 100.0 3220 100.
0
The area of greatest interest here is what type of lesion was most commonly excised by shave
biopsy. This was rarely performed for lesions found to be malignant or potentially malignant.
The differences are significant, (Chi squared test with four degrees of freedom = 30.04;
p<0.001).
Examination of the margin of normal tissue removed with each specimen
In the following analyses some data also from the Intervention City are included. As has been
described above in detail, six months of data were collected in the Intervention City before an
intervention was provided. Therefore the data were not subject to any experimental effect.
These data are included (an addition of about 20% more data) in order to increase the power
of some of the group analyses.
— 98 —
Table IV.17
Analysis of the of the geometric mean margin of excisions in millimetres (and
estimated 2.5, 97.5 percentiles of distribution of margins) by the diagnosis,
age and sex of the patients
Hutchinson’s
Total
Benign
melanotic freckle
lesions
n=21
Melanomas Significance
p
n=151
n = 2914
Overall
3
2.8
(0.8, 8.3) 2.7
(0.8, 7.6) 5.9
(1.8, 17.5) 5.1 (1.2, 17.8)
b, c
b
275a
Sex
male
1 405
3.1
(0.9, 8.8) 3.0
(0.9, 8.0) 4.5
(2.0, 9.6) 5.1 (1.2, 18.0)
female
1 850
2.6
(0.7, 7.9) 2.5
(0.7, 7.2) 7.3
(2.1, 22.9) 5.1 (1.2, 17.7)
Age group (years)
a
≤ 15
444
2.6
(0.8, 6.7) 2.6
(0.8, 6.7) -
3.3 (0.9, 10.2)
16-20
579
2.5
(0.7, 6.8) 2.5
(0.7, 6.9) -
2.7 (0.7, 8.3)
21-30
888
2.7
(0.8, 7.7) 2.7
(0.8, 7.5) -
5.0 (1.6, 14.0)
31-40
618
2.8
(0.8, 8.1) 2.7
(0.8, 7.6) -
4.7 (1.4, 13.6)
> 40
704
3.5
(0.9,11.2) 3.2
(0.9, 9.1) 5.8
b, d, e
(1.8-16.9) 5.5 (1.3, 19.7)
Numbers of benign and malignant lesions do not add up to the total because of missing data and
the exclusion of 130 lentigines, 51 dysplastic naevi, and 8 'other' lesions.
Based on sex and age-adjusted mean margins:-
b
p < 0.05 for all lesions
c
p < 0.05 for benign lesions
d
p < 0.05 for Hutchinson’s melanotic freckle
e
p < 0.05 for melanomas (levels I+)
The mean margin of normal tissue excised around the lesion was 2.8mm. It was greater
around melanomas (5.1mm) and even greater around Hutchinson's melanotic freckles
(5.9mm), while it was a little less than the overall for the benign lesion (2.7mm). The overall
differences were significant (p < 0.001) and remained significant when adjusting for sex
(p<0.05). The difference between size of the margin remained significant for the subgroup of
the benign lesions was also significant to the same level (p < 0.05).
The margin was smaller for females (2.6mm overall) than males (3.1mm overall), (p < 0.05).
There was no sex difference for the margins of melanomas and the sub-group of benign
— 99 —
lesions (p< 0.05). The greater margin for Hutchinson's melanotic freckle (of which there were
only 21) among females (a trend in the opposite direction) was not significant.
There was an age effect. Those 40 years old and under had significantly smaller margins
around their lesions than those older, overall. This effect was apparent for both benign lesions
and melanomas, (all Hutchinson's melanotic freckles were in those older than 40). The
differences between these groups were significant (p < 0.001) when adjusting for sex.
The mean margins of Hutchinson's melanotic freckles were significantly smaller at 4.2mm
than those referred at 7.0mm, (p = 0.043). For the margins around melanomas (including
Level 1 and above) only patient age (p = 0.001) was significant. For other lesions the
differences were insignificant (p> 0.05).
Table IV.18
Geometric mean margin of excisions in millimetres (and estimated 2.5, 97.5
percentiles of distribution of margins) by the number of referrals
Hutchinson’s
Number
Total
Overall
Benign
melanotic
Melanom
lesions
freckle
as
n = 2914
n=21
n=151
s of
referrals
0
2709
2.8
(0.8, 8.0) 2.7
(0.8, 7.5) 7.1
(2.2, 21.0 4.7 (1.3, 14.
1+
278
3.2
(0.8,10.2 3.0
(0.9, 8.5) 4.2
(1.6, 10.0 6.2 (1.2, 25.
(Data are from both Rockhampton, the six months before the prospective collection and the
two years of the prospective collection, and Mackay, the six months before the prospective
collection)
Lesion that were referred (the minority) had margins that were not significantly greater at a
mean of 3.2mm rather than those not referred at 2.8mm. This trend was apparent also among
benign lesions (2.7mm referred and 3.0mm not), melanomas (6.2mm referred and 4.7mm not),
but was reversed among HMFs (7.1mm referred and 4.2mm not) where the effect was
significant (p < 0.05).
The effect of diagnosis and reason for excision on the margin are displayed in Table IV.19.
— 100 —
Table IV.19
Geometric mean margin of excisions in millimetres (and estimated 2.5 and
97.5 percentiles of distribution of margins) by the diagnosis, and reason for
the excision and patient pressure as perceived by the doctor (1 = none: 5 =
maximum)
Factor
n
Benign
HMF
Melanom
lesions
n = 21
as
Overall
n = 2 914
n = 151
Reason for excision
Exclude
1 633
3.0 (0.9, 8.4) 2.9
(0.9, 7.7) 5.8 (1.6, 18.8 4.7 (1.2, 15.4)
Discomfor
17
2.4 (0.7, 6.5) 2.4
(0.7, 6.5)
-
t
1
Cosmetic
13
2.4 (0.7, 6.7) 2.4
(0.7, 6.7)
-
2.9 (0.5,11.4 2.8
(0.5, 10.8 5.0
6.3 (1.6, 21.5)
3.4 (1.0, 9.4)
3.1 (1.1, 8.0) 5.2
(1.2, 18.8 5.3 (1.6, 15.6)
2.9 (0.8, 8.2)
2.9 (0.9, 7.8) 5.6
(2.5, 11.8 4.3 (0.7, 18.3)
3.0 (0.8, 8.7)
2.9 (0.8, 8.1) 7.1
(1.2, 33.1 4.8 (0.6, 26.2)
2.4 (0.7, 6.4)
2.4 (0.7, 6.4) -
malignanc
y
2
Other
95
Patient pressure to
excise
1†
48
8
2
39
1
3
54
7
4
37
8
— 101 —
2.9 (12., 6.0)
5*
2.5 (0.6, 7.3)
2.5 (0.7, 7.3) -
-
22
3
†
'No patient pressure'
*'Patient pressure only reason for excision'
Lesions were given significantly more generous margins of normal tissue when excised to exclude
malignancy (3.0mm) rather than for reasons of discomfort or cosmetic (2.4mm), although the margin
was nearly as generous for 'other' reasons 2.9mm), (p < 0.05). This effect was significant also for
the subgroup of benign lesions, (p < 0.05).
Lesions were given a significantly more generous margin of normal tissue around those for which
there was greater patient pressure (for example lesions for which the doctor perceived maximum
pressure had a mean 2.5mm margin of normal tissue) than those with less (for example lesions for
which the doctor perceived no pressure to excise was associated with a margin of 3.4mm),
(p < 0.05). Similar trends were associated with benign, and melanomas, but not with HMFs. The
differences between the cells overall was significant (p < 0.001). Multi-variate analysis was not
significant except for the benign lesions (p < 0.001).
The effect on the doctors' characteristics on the margin of excision was examined by the histological
diagnoses, Table IV.20.
— 102 —
Table IV.20
Geometric mean margin of excisions in millimetres (and estimated 2.5, 97.5
percentiles of distribution of margins) by diagnosis, and characteristics of the
doctor
Benign
n
Overall
lesions
HMF
Melanomas
n=21
n=151
n = 2914
Year of graduation
≤ 1986
1976-1985
91
2.4
(0.7, 6.8) 2.4
(0.7, 6.6) 6.2
(0.9, 32.0 5.2 (1.6, 15.2)
172
2.7
(0.8, 7.7) 2.7
(0.8, 7.3) 8.1
(2.5, 24.1 4.6 (1.4, 13.5)
(3.4, 11.4 4.1 (0.9, 14.6)
2
1966-1975
613
2.8
(0.7, 8.3) 2.7
(0.8, 7.6) 6.3
< 1966
538
3.3
(0.9, 9.9) 3.1
(0.9, 8.9) -
2161 2.7
(0.8, 7.7) 2.6
(0.8, 7.3) 6.9
(1.9, 21.9 4.5 (1.0, 15.6)
RACGP
716
2.9
(0.8, 8.5) 2.8
(0.8, 7.6) 6.3
(1.3, 25.8 5.9 (2.1, 15.3)
surgeon
381
3.6
(1.0,11.0 3.4
(1.0, 9.5) 5.0
(2.1, 10.8 6.6 (1.3, 27.1)
dermatolog
17
1.9
(0.2, 7.4) 1.9
(0.2, 7.4) -
3.2
(0.8, 9.7) 3.0
(0.9, 8.5) 5.7
(2.2, 14.2 5.5 ( 1.3, 19.8
2.4
(0.7, 6.6) 2.3
(0.7, 6.1) 4.4
(0.9, 16.7 3.8 (0.7, 14.3)
3.1
(1.0, 7.9) 3.0
(1.0, 7.6) 15.5 b
2.5
(0.7, 7.1) 2.4
(0.7, 6.7) 8.0
5.9 (1.6, 19.2)
Type of doctor
not
RACGPa
-
istb
Number in practice
1
82
1
2
54
6
3
5.4 (2.6, 10.5)
77
0
4+
( 1.0, 48.7 4.7 (1.9, 10.8)
69
9
aRACGP = affiliated with the Royal Australian College of General Practitioners (either as Fellow
of Member)
— 103 —
bThere was one dermatologist working part-time in the control city
There was a significant difference in the distribution of figures across all the groups with respect
to year of graduation (p < 0.001): those who graduated most recently provided smaller margins of
normal tissue around the lesion (2.4mm for those graduating since 1985) compared to earlier (for
example 3.3mm from those graduating before 1966). This effect was significant for the benign
lesions too (p < 0.001), but not for the melanomas and Hutchinson's melanotic freckles.
With respect to type of doctor, those without any affiliation with the RACGP had a smaller margin
of normal tissue around their excised lesions (2.7mm) that those with (2.9mm). Surgeons had the
largest margins (3.6mm). There was only one dermatologist who managed only 17 lesions in this
manner (1.9mm margins). These differences were significant at the p < 0.001 for lesions overall
and the benign ones by uni-variate analysis, and the differences in the Hutchinson's melanotic
freckle was at the p < 0.05 level.
Although the differences in the groups was significant (p < 0.001 overall and for the benign
lesions) for the cross tabulation of numbers in the practice by diagnosis), no clear pattern emerges:
smaller margins were left by those in 2-person and 4+ person practices (3.2 and 3.1mm
respectively) than in one-person and three-person ones (2.4 and 2.5mm respectively) overall. A
similar pattern was evident for benign and malignant lesions.
Multi-variate analysis
Only patient age (p=0.001) and type of doctor (p=0.054) remained significant with multivariate
modeling.
— 104 —
F Results of the intervention component of the study
The results of the intervention are presented.
Comparison at baseline
In the six months before the date of introduction of the intervention, a total of 1,358
melanocytic lesions were reported by the pathology laboratories: 55% from the control
community, and 45% from the intervention community (Table IV.21). The distributions of
excised cutaneous melanocytic lesions by sex and age of patients and site were very similar
for both cities.
Table IV.21 Comparison of characteristics of patients having lesions excised at baseline and
after the intervention, between and within cities
Baseline
Control
City
Post-intervention
Intervention
City
n
%
n
%
752
55
606
45
male
326
44
277
46
female
425
56
329
< 20
206
28
20-29
197
30-39
> 40
Control City
p
Intervention
City
n
%
n
%
2468
55
1997
45
1013
42
897
45
54
1426
58
1091
55
166
27
637
26
461
23
26
173
29
694
29
510
26
162
22
117
19
538
22
454
23
182
24
149
25
551
23
549
28
28
(1,87)
30
p
Total excised
lesions
Sex
0.396
<0.05
Age years
0.680
<0.001
Median age
(range)
28
(0,94)
27 (7,93)
0.956
(2,90) <0.05
Site of lesion
head/neck
170
24
132
22
518
22
418
21
trunk
375
52
349
59
1315
56
1043
53
arms
76
11
47
8
240
10
231
12
legs
89
12
63
11
270
11
241
12
buttocks
5
1
4
1
28
1
21
1
0.187
— 105 —
0.318
Although the percentage of lesions that were submitted for histology which were non-invasive
was lower in the control city (96.1%) than in the intervention city (98.2%), (p < 0.05), there
was no difference by city in the proportion of benign lesions
—that is, lesions that were
neither invasive nor potentially malignant, (p = 0.73) (Table IV.22). The median thickness of
the melanomas excised in both cities was similar (p = 0.34).
Comparison after the intervention
During the 24 months after the intervention was introduced, a total of 4,465 lesions were
excised and reported in the two study cities, of which 45% were excised in the intervention
city, the same proportion as at baseline (Table IV.22).
— 106 —
Table IV.22
Comparison of characteristics of excised melanocytic lesions at baseline and
after intervention between and within cities
Baseline
Control
Intervention
City
City
Total
Total excised
lesions
Diagnosis
benign naevus
lentigo
dysplastic naevus
Hutchinson’s
melanotic
freckle
melanoma
other
Total potentially
malignant
lesionsb
Post-intervention
Total
%
%
752
666
39
10
3
32
2
P
60
6
8
9
5
1
53
7
23
18
0
4
0
6
15
7
Control City
Total %
2468
2210
101
27
89
4
3
0.01
2
1
2
1
13
113
4
Average
a
Total
617
9
0
4
1
1
5
0
47
153
45
39
Intervention City
1997
3
28
1
4
11
0
Percentage of
96.1%
98.2%
81
7
4
27
114
7
1
6
0
lesions that were
(94.8-
(97.1-
non-invasiveb c
97.5)
99.2)
94.0%
93.6%
(92.3-
(91.6-
95.7)
0.13
3
30
82
1
8
26
—
30
82
2
0.02
(95.9-
(94.9-
7
97.3)
96.7)
93.8%
88.8%
0.73
(92.8-
(87.4-
95.5)
1
94.8)
90.2)
0.40
0.60
0.34
0.60
0.50
thickness (mm)
(0.10-
(0.10-
4
(0.2-11.0)
(0.10-
(range)
4.20)
14.0)
(95% CI)d
Percentage of
lesions that were
CI)d
Median melanoma
68
224
95.8%
malignantb c (95%
499
1621
145
83
96.6%
potentially
Average
a
0.73
1
Total melanomas
level I
levels II+
unknown level
neither invasive nor
%
— 107 —
13.0)
8
26
—
Lesions for which there were missing data for a particular variable, are excluded.
a
Six-monthly average for direct comparison of counts with baseline phase (expected values
calculated based on the baseline total);
b
Potentially malignant lesions include melanomas, Hutchinson’s melanotic freckle and
dysplastic naevi;
c
as a percentage of the total number of melanocytic lesions;
d
95% confidence intervals.
To compare the number of lesions excised during the six month period before
the
intervention with those after the intervention, the latter total (comprising 24 months) was
divided by four to derive the average in both time intervals (of six months). The average six
monthly number of lesions excised in both cities decreased by 242 (135, 18%, in the control
city and 107, 18%, in the intervention city) after the intervention was introduced. However
the percentage of excised lesions that were neither malignant nor potentially malignant fell
significantly (p < 0.001) from 93.6% at baseline to 88.8% in the intervention city only (Table
IV.22), a difference of 4.8% (95% confidence interval of 2.4% - 7.2%).
There was also a decrease compared with the percentage of lesions neither malignant nor
potentially malignant (93.8%) that were excised in the control city during the postintervention surveillance period (p < 0.001). Further, no change from the baseline proportion
of 94.0% was observed in the percentage of benign lesions excised during surveillance in the
control city. The magnitude and statistical significance of the intervention effect was not
diminished on adjustment for sex, age group, and site of lesion. Over the same period the
percentage of melanomas excised in the intervention city rose from 2.5% to 5.7% while in the
control city they remained nearly constant (4.3% baseline and 4.6% post intervention).
In contrast to the similar sex and age distributions in both cities at baseline, lesions were
excised from proportionately more males in the intervention community (p = 0.017), and the
ages of patients were significantly higher in the intervention community than in the control
community (p = 0.0004) (Table IV.21). The site distributions of the excised lesions remained
similar for both cities (p = 0.318).
The reason for excision is described in Table IV.23:
— 108 —
Table IV.23
Reason for excision of lesions
Post-intervention
difference
between
Intervention
Control
cities
City
%
City
%
• to exclude malignancy
1871
78
1241
72
• discomfort
237
10
247
14
• cosmetic
188
8
157
9
• other
110
5
72
4
p
Reason for excision given
by excising doctor
<0.0001
Significantly fewer doctors in the intervention community than in the control community
offered ‘exclusion of malignancy’ as the reason for excision (p < 0.0001) (Table IV.23).
The pressure that the doctors felt themselves to be under from the patients is tabulated below
in Table IV.24:
Table IV.24
Perceived patient pressure on excising physician
Post-intervention
difference
between
Intervention
Control
cities
City
%
City
%
532
22
399
24
426
18
311
19
perceived
655
27
391
23
2
474
20
299
18
3
314
13
275
16
p
Patient pressure to excise
perceived by excising
doctor
1 no pressure
0.88*
4
5 excision fully due to
patient pressure
* Test for trend
— 109 —
Following the intervention, doctors in the intervention community perceived significantly less
pressure from patients to excise melanocytic lesions than doctors in the control community
(p < 0.005). However similar proportions of lesions were excised as a direct result of patient
pressure. The differences in trend across the cities of excision in relation to patient pressure is
not consistent. The test for trend, which treats the pressure scale as continuous, achieved p =
0.88 only. Therefore it must be assumed that there is no significant difference as a
consequence of the intervention on perceived patient pressure.
Population changes between the cities during the study period
One concern is that there might be changes in each city to account for any differences found
between them apart from the intervention delivered. One difference might have been
differential changes in population. This would be important because many other changes
might be consequent, including changes in the doctor workload, which might alter the rate at
which doctors excised lesions.
The populations in each city were investigated by examining the relevant Australian Bureau
of Statistics data, Table IV.25.[121]
Table IV.25
Population changes in the two cities during the study period
1998
1991
Percentage
Percentage
mean annual
increase
increase
Mackay statistical district
49 480
53 225
7.57
1.51
Rockhampton statistical district
59 760
63 598
6.42
1.28
In summary each city had undergone similar growth (under 2% in each city between the
census years of 1986 and 1991).
There were no differences in pathology reporting management. Nor were there any other
known relevant events that might alter rates of excision in either population.
— 110 —
Use of camera and acceptability of intervention
The results of the survey, which was a postal questionnaire, are displayed in Table IV.26.
Table IV.26 Responses to a questionnaire sent to 64 primary care doctors in the intervention
city about the processes of using a camera
Coding
Q No Question
Q1
Q2
Q3
Q4
Q5
Q6
How many times did you use the camera per week?
0
<1
1
2
3
4
5
10
Missing
Where was the camera kept?*
Reception
Treatment room
Consulting room
Other
Missing
n
3
20
23
6
4
1
6
1
0
1
2
3
4, 5, 6, 7
10
37
14
3
0
Did you have technical difficulties?*
Yes – no comment
Yes – quality of the pictures inadequate
Yes – time taken/loading film problems
No
Missing
1
3
4
2
1
4
6
52
1
Where did you store the pictures?
Patient's main file
A second patient file
A special photograph file
Missing
1
2
3
53
6
3
2
What was the average number of photos per patient
per visit?
1
2
3
Missing
Was there provision for patients to take photos away
with them?
Never
About half the time
always
Missing
— 111 —
50
10
2
2
1
2
3
49
6
7
2
* Coding assigned after the data were collected from open comments.
— 112 —
Continued…
Table IV.26
Responses to a questionnaire sent to 66 primary care doctors in the
Continued…
intervention city about the processes of using a camera
Q No Question
Coding
n
1 and 2
1
2
1
51
8
4
1
2
27
33
4
1
2
30
28
6
1
2
46
13
5
1
2
19
39
6
1
2
45
14
5
1
2
44
14
6
1
2
52
6
6
Q.11 Did you reduce unnecessary excisions?
Yes
No
Missing
1
2
31
29
4
Q.12 Did patients attend for follow-up?
Yes
No
Missing
1
2
36
22
6
Q7
a
b
c
d
e
Q8
Are photos accurate in respect of:—
size?
Yes and No
Yes
No
Missing
colour overall?
Yes
No
Missing
colour variation?
Yes
No
Missing
characteristics of edges
Yes
No
Missing
surface features?
Yes
No
Missing
Were the photos helpful in documenting changes
later?
Yes
No
Missing
Q9
Was follow-up more accurate?
Yes
No
Missing
Q.10 Were photographs reassuring for patients?
Yes
No
Missing
— 113 —
Almost all of the doctors (98%) in the intervention city who initially agreed to participate
reported using the camera in their practice, with the modal frequency of use being once every
week. Two doctors indicated that they used the camera very infrequently (one lost the camera
after a year; and the other used the camera for other than managing naevi). The camera was
kept in a ‘treatment room’ by 58% of doctors (37/64), while another 16% (10/64) kept the
camera in another room outside their own consulting room. Difficulties were apparently few:
83% of doctors experienced none; 10% had some difficulties loading new film; 6%
complained about the quality of the pictures. Eighty five percent stored the photograph with
the patient’s main clinical record; 10% used a secondary patient file; and 5% used a special
storage file for photos. Most doctors (81%) usually photographed only one lesion per patient.
Usually they did not provide patients with pictures of their own lesions routinely, although
20% occasionally did. About two-thirds of doctors thought that patients attended for followup, though this was not documented formally. Photographs were reported as being more
helpful in recording changes in size and outline characteristics, than in recording colour and
surface features (Table IV.26). Responses to overall usefulness indicated that the majority of
doctors found the cameras worthwhile for objectively documenting changes or achieving
more accurate follow-up of lesions, and very useful for reassuring patients. Less than onethird reported that they had consciously reduced the frequency of unnecessary excisions as a
result of using the camera.
— 114 —
G
G.1
Discussion
Methodological problems
The following issues are discussed:Errors of omission
Each pathology company was assumed to be diligent in ensuring that copies of every report
was made available for the study. No formal checks on this could be made. The protocols
developed by each laboratory appeared to be foolproof. It is unlikely that there would be any
systematic bias in any such possible effect (that is, that some groups would be more likely to
be under-reported than others) because any such error presumably would arise as a
consequence of the failure of protocols within the laboratory.
Assumption that all excised lesions were submitted for histopathology
Every melanocytic lesion excised by local practitioners in the study was assumed to have been
submitted for histological examination, since in Queensland with its very high annual
incidence rate of melanoma[128], this is standard medical practice.[111, 143] However it is
possible that some lesions were not submitted for histology. This is likely to be affected by the
diagnosis. Lesions under suspicion of being melanomas may be more likely to be submitted
than those thought benign, as might patient pressure, and various doctor characteristics.
Therefore the ratio of benign to total melanocytic naevi as an absolute measure of doctor
performance must be regarded as indicative only. Whether relative comparisons between
ratios used in the different analyses are subject to threats to validity as well depends on
whether the ratio is likely to be influenced by differences in the probability that doctors were
more or less likely to submit for histology lesions with different factors operating. It is
possible for example, that lesions removed for cosmetic reasons were less likely to be
submitted for histology than those for exclusion of malignancy. Similarly those thought to be
benign clinically may have been less likely to be submitted for histopathology than those
thought to be malignant.
It is worth speculating what such an effect would have on the results. The effect presumably
would be to diminish the difference between the result of histology from reason for excision,
and the clinical diagnosis. Therefore if there is an error arising from failures to submit lesions
differentially, the described differences is likely to produce an underestimate of the true ratio
of excised melanoma lesions that are melanomas.
— 115 —
Generalisation to Australian practice
The cities studied might not be representative of Australia. There may be characteristics of the
city that make generalisation of the results to other parts of Australia hazardous. Even as
representative of regional Australia, these cities may have idiosyncrasies both as a population
and as a medical community. Therefore the results cannot be generalised beyond provincial
Queensland with any confidence.
Gold standard of diagnosis
The gold standard of the result was taken to be the pathology result. In general this is the gold
standard as applied to clinical medicine. There are suggestions that there may be flaws with
this approach for melanoma. Perhaps the diagnosis of melanoma is over-diagnosed
pathologically, a suggestion based on the divergence between the relatively stable death rate
from melanoma and rapidly increasing incidence rates being reported.[144] However direct
evidence coming from pathologists worldwide who achieved over 92% concordance with the
diagnosis of melanoma, suggest otherwise.[74] Certainly to have undertaken a validity check
on this area (which would have required samples of lesions to be examined by other
pathologists) would appear to have been unnecessary, and would have involved expense
beyond this study's resources. In particular the intervention data are analysed by relative
changes in the ratios of different diagnoses. It is difficult to imagine how a systematic effect
would have biased the results from this potential source of error.
Validity of questionnaire responses
Clinicians answered their questionnaires after getting the results of the histology. This means
that knowledge of the histological diagnosis could have influenced their response, to the
reason for excision, for example. Ideally the study would have imposed an artificial delay in
the clinician getting the results so that they could be administered the questionnaire before.
This would have been impossible to arrange or to justify on ethical grounds because it can be
imagined that patients might have been harmed should treatment have been delayed as a
consequence. Other measurements (for example margin of normal tissue around the lesion)
were not subject to this effect.
Again it is worth speculating what if any such an effect would have on the results. The effect
presumably would be to diminish the difference between the result of reason for excision, and
the clinical diagnosis, from the histology. Therefore if there is an error arising from
differential invalid questionnaire responses, the described differences is likely to be an
underestimate.
Validity of the concept of patient pressure
— 116 —
Patient preference is clearly a subjective notion on the behalf of the treating doctor. At face
value the measurement could be criticised on this basis, (that it subjective to the doctor and
does not represent the reality of whether patients were or were not, consciously or
unconsciously, putting pressure on their doctors). It is certainly possible.that doctors may be
over-sensitive or under-sensitive to the perception of pressure. However it is argued that the
item of interest is the management of the lesion, and therefore the doctors' perceptions, the
greatest determinant of management, are of greater interest that that of patients. Whether a
lesion is excised or not will be more sensitive to the doctor's received notion of what the
patient wants than the patient's actual pressure (or not) on the doctor. Doctors often
misapprehend their patients' fears, concerns, and expectations of the consultation, particularly
when they do not ask explicitly.[130, 145, 146]
Design of the experimental component of the study
The greatest problem for the intervention component of the study is that of the study design
outlined above. This was a quasi experiment in which there are several possibilities to explain
the result. Those possibilities are related to local events that might have influenced the
intervention city but not that acting as control. Therefore the result should be regarded as
preliminary and not definitive. Replication of the same result in other sites would be very
suggestive that the provision of an algorithm together with a camera improves the clinical
accuracy of melanocytic skin lesion management in general practice.
The effect of financial inducements to excise
One possible influence which this study has not taken into account is that of financial
remuneration for excisions. It is possible that GPs were better rewarded for performing
excisions than other clinical services for patients, and this either consciously or unconsciously
encourages them to undertake excisions more often than if such possible perverse incentives
did not exist. This study made no attempt to study this effect. Doctors were likely to have
been very sensitive to such suggestions, explicit or implicit, and to study such an effect
without threatening the success of the rest of the study would have been difficult. Therefore it
is not possible to predict how changes in the funding of doctors services with respect to
managing skin excisions would operate. It is known that such changes influenced GP activity
in the UK, where changes to the funding arrangements in primary care led to a large increase
in GP skin excisions for melanoma (from less than two melanomas per year in the nine years
prior to the 1990 New Contract to more than 13 per year after it in South East Scotland).[98]
— 117 —
G.2 Clinical significance of the findings of the descriptive component of the Naevus
Management Study
Age and sex distribution of patients from whom melanocytic lesions were excised
The broad observations that the bulk of excisions occurs in the under 40 age group, and
among females, are confirmed. The exact age and sex incidence of the management of
melanocytic lesions in general practice in these cities are not calculated because 1) this would
have involved measuring the population rates, and 2) there are better data for the whole of
Australia in Chapter 2. These data also provide confirmation that most melanocytic lesions
excised are benign. The ratio of benign lesions to malignant or potentially malignant is very
high.
Referrals of melanocytic skin lesions
Most melanocytic lesions were managed by primary care doctors. There was little evidence of
referral even within practices (from one general practitioner to another, for example). These
data in part address the shortcoming of those analysed in Chapter III (the series of
melanocytic lesions in one laboratory) in which it was not possible to estimate what
proportion of lesions came from primary care and which from specialist or hospital care.
Clearly most melanocytic skin lesions were excised from primary care in provincial
Queensland. Very little referral took place in the management of melanocytic skin lesions in
general practice in these provincial cities. This is in contrast to parts of Europe and the USA,
where referrals to specialists or hospital services are the mainstay of possible malignant
naevi.[90]
A greater proportion of lesions ultimately found to be melanomas were referred presumably
because of increased concern that these lesions should be treated definitively. The explanation
for the greater proportion of lesions ultimately found to be HMFs may be that they often are
large and found on the face.
These finding cannot be generalised to the whole of Australia since this study considered only
provincial Queensland, where it is possible that patterns of melanocytic skin lesion
management are different from environments where more relevant specialists are available.
Nevertheless the data have implications about the best site of any intervention designed to
improve the management of naevi among Australians in provincial Queensland.
— 118 —
Reasons for excising melanocytic skin lesions
Of great interest is the new observation that most lesions are excised to confirm or exclude
melanoma. This observation, as seen from the caveats above, is more likely to be an underestimate than over-estimate. Over three quarters of melanocytic lesions are removed because
of some concern about malignancy.
Patient pressure to excise
A second important new observation concerns the estimate of patient pressure. As discussed
above, this might not represent the true incidence of patient pressure, but rather what is
perceived by the doctor. Perceived patient pressure is the factor most likely to influence
medical management. It is very high: the great majority of excisions are perceived by the
excising doctor to be occasions of pressure on them. A great minority of lesions are perceived
to be free of patient pressure. This suggests that addressing patient concerns is an important
matter to consider in terms of managing consultations in which melanocytic lesions are a part.
Steps that are felt by the doctor to reduce patient anxiety might be predicted to reduce the
number of benign ('unnecessary') excisions.
Excision margins
In summary, wider excisions of skin melanocytic lesions appeared to be performed by older
and more experienced doctors, on older patients, and for suspicious or frankly malignant
lesions.
The mean excision margin was small at less than 3mm, although it was greater for lesions
suspected of being, and those that actually were, melanomas. This seems to follow the move
towards smaller excisions of tissue evident from other reports.[112]
Perhaps surgeons excised with greater margin than other doctors because the lesion had a
greater probability of a working diagnosis of malignancy, or because the lesions were thought
to be technically difficult by the referring doctor. The reason for the association of a greater
margin of excision among doctors affiliated with the Royal Australian College of General
Practitioners compared with other non-specialists is not known.
The less generous margins of lesions removed by doctors who felt themselves to be under
greater pressure to excise may reflect their decreased concern that these lesions were
malignant. Whether an increased concern explains the greater margins of lesions from older
patients, or whether this reflects an interest in obtaining the better cosmetic effects of smaller
rather than larger scars on young patients, is an issue for speculation. Support for the latter
idea comes from the trend for smaller excisions of benign lesions from females, who might be
expected to be more concerned about the cosmetic consequences of scars than males.
— 119 —
G.3 Clinical significance of the findings of the intervention component of the Naevus
Management Study
The results coming from this Chapter suggest that a simple intervention might alter clinical
behaviour to positively influence the diagnostic process.
The trade-off between over-excision and missing melanomas
It is an established principle of clinical epidemiology that altering the threshold of an
imperfect diagnostic cut-off point will alter both the sensitivity and the specificity of a
diagnostic test in opposite directions.[147] This has consequences for the acceptance of a new
diagnostic test.
One method of analysing the potential benefits of any medical intervention is to estimate the
number-needed-to-treat (NNT).[148] This number represents the number of patients who
must be intervened with for one to benefit. Ideally this number would be 1:1.
In this setting the NNT would be represented by the number of excisions patients needed to be
subjected in order to remove one melanoma. We have shown that the NNT can be calculated
from the 4% figure of melanomas removed. It is calculated from the inversion of this figure:
100/4 or 1:25. In other words 25 lesions must be removed to remove one melanoma. This
figure might be revised to accommodate the 22% of lesions removed for reasons other than to
exclude malignancy derived earlier in this Chapter (see Table IV.9 and associated text). This
modifies the figure to 78/4, or about 1:19.5.
How does this figure compare to others? Investigators in Western Australia studied a group of
4 103 people aged 40-64 from the electoral roll in Geraldton to estimate the number of skin
cancers. A dermatologist examined them all by whole-body examination. A suspicious
melanoma or a 'suspicious pigmented lesion' was identified among 102, so that excision was
recommended. From these, 14 were later shown to be melanomas.[57] This represents a ratio
of 102/14 which yields a NNT of 1:7.3.
In a survey, GPs were asked what the ratio of benign to malignant melanocytic lesions should
be. There was a range of responses, from 31% of respondents who thought it should be less
than one, 9% who proposed a ratio of 1:1, and of the rest (60%), most gave 10:1.[149] This
can be converted crudely into NNT for the majority into 1:11. This lies between the figure
derived from the Western Australian data and those produced here.
— 120 —
Chapter V
Primary prevention – another approach?
Introduction
The previous chapters (II and III) have shown that general practice is the site of considerable
work load of care for skin cancer. A large burden is carried by the management of melanoma.
Included in this management is the diagnostic strategies for addressing the differentiation of
melanoma from banal naevi.
Chapter IV demonstrated that most management of naevi of the skin is in fact separating
benign from malignant pigmented lesions. It also showed that a large proportion of lesions
excised are a consequence of the perceived pressure doctors feel themselves to be under from
their patients. The chapter has concentrated on the improvement of diagnosis to increase the
specificity of diagnosis whilst maintaining sensitivity.
This chapter will now concentrate on other areas of preventing or reducing mortality and
morbidity from skin cancer from a general practice perspective.
Interventions outside general practice
Before enlarging on the possible interventions that might be engendered from within general
practice, it is important to look at the public health interventions that have been generated
from outside the clinical system – that is, from health promotion. Considerable effort has been
undertaken in trying to get people to avoid the damage of ultraviolet sunlight. This is based on
the premise that reducing the ultraviolet on the skin will reduce the incidence and secondary
damage caused by skin cancer. Australian public policy in this regard started in the 1960s.[19]
However there are possible problems with this approach.
Problems with a primary skin cancer prevention approach
There may be insufficient evidence
The problems in this regard have been described in Chapter I. Ultimately the level of evidence
reached will be a value-laden judgement. Each worker is likely to reach different conclusions
based on their variable thresholds for what is an acceptable level of evidence.
— 121 —
The ethical need for increased stringency with regard to preventive measures
Some health workers and commentators have been highly critical of preventive measures in
general. Their concern is that every preventive measure carries with it a cost. The cost may be
direct (for example, in this case, the fiscal expenditure on advertising borne by the
community; or the emotional cost in the form of distress of causing people worry about
cancer), indirect (for example the costs, either monetary or in the form of loss of amenities,
consequent on people avoiding being outside in sunny weather), or in the form of opportunity
costs (for example the alternative healthy activities that people might have undertaken if they
were not focussed on sunlight avoidance). The costs have rarely been balanced against the
supposed benefits.[150] To develop this theme further requires the synthesis of the previous
point as well: it is argued that when addressing the health of people who are well, increased
stringency is required for the weighing of the benefit of any preventive activity.[151] This is
based on the duty of the medical and health promoting professions to first do no harm (the
principle of primum non nocere generated by Hippocrates).
The anomaly with occupational exposure to sun and skin cancer rates.
It has already been shown from the literature under ‘Deciding if the association between
sunlight and sun cancer is causal’ in Chapter I that there may be circumstances in which a sun
tan provides protection for some people. Perhaps there is a group of people who are relatively
protected by developing a tan. The tan protects them against developing skin cancer from
intermittent sun exposure on an untanned skin.
The importance of this lies in the ethics of harming some sectors of the population by sending
a message to the whole community about protection against the sun. Even though the majority
might benefit from interventions designed to assist avoiding the sun, there are some subgroups who might be harmed.
Types of sun avoiding interventions
The most important sun avoiding intervention has been the 'Slip Slap Slop' campaigns of the
1970s and 1980s in Australia. They are still current today. Campaigns started in Queensland
in the 1960s.[19] They are now initiated in all parts of Australia by the cancer societies of
each state in the Spring (usually November) of each year. This is called National Skin Cancer
Awareness Week.[152] The main focus is on primary prevention. That sentence hides a
— 122 —
considerable debate: the Australian Cancer Societies are seriously considering the introduction
of campaigns to increase the detection of undiagnosed melanoma in an attempt to reduce its
morbidity and mortality). A target of the Australian Cancer Societies is to reduce the incident
ultraviolet to 60% of the 1988 value.[153] Theoretical estimates of the benefits of using a
sunscreen with a sun protective factor of 15 regularly during the first 18 years of life would
reduce the lifetime incidence of non-melanocytic skin cancer by 78%.[154] This assumes no
harmful effect of sunscreen: the benefits in terms of melanoma incidence would be tiny in
comparison.
Estimating the harm from a primary care approach
The opportunity to examine the effects of a primary prevention skin cancer program on the
excision rate of melanocytic naevi was afforded during the phase of collecting data in the city
of the descriptive component of the Naevus Management Study described in Chapter IV.
Rationale for the study
The possibility that primary prevention might actually result in harm has been outlined above.
However in the area of primary prevention against skin cancer there has been very little
investigation into this aspect. A search of the literature undertaken at the time of undertaking
the analysis did not reveal any such estimates of harm.
Campaigns encouraging the avoidance of sunlight usually mention skin cancer. This may
encourage people to present to their doctors skin lesions which might be cancers, most of
which will be benign. If this occurs, it will generate a cost to primary prevention which has
not been described.
Description of the study
The study from which these data have been derived has been described in detail in Chapter
IV. For this analysis there was collaboration with both Adèle Green and a statistician, Diana
Battistutta. Some of the data have been published, (Appendix)[155] and some of the
discussion in this chapter have been published also (Appendix).[89, 156] The number of
melanocytic excisions submitted for pathology were tabulated by every week between
November 1990 and March 1993. The melanocytic lesions were divided into the following
two groups of lesions: 1) all levels of melanoma and all potentially malignant lesions
(including Hutchinson's melanotic freckles, and dysplastic naevi); and 2) all other (benign or
banal) melanocytic lesions. The rationale for including Hutchinson's melanotic freckles and
dysplastic naevi is because their excision could improve patients' health either directly (HMFs
— 123 —
for example are thought to be pre-malignant lesions that eventually develop into melanomas),
or indirectly because their excision affords a diagnosis of a risk that requires increased
surveillance, such as dysplastic naevi. The effect of the campaigns on the distribution of the
excisions, and the proportions of the benign and malignant-or-potentially-malignant lesions
was studied. However first we had to adjust for the effect of season on the distribution of the
excisions. There is evidence that naevus melanocyte activity is greater during sunny seasons
of the year.[131, 138] Also the consultation rate for naevi has been shown to be strongly
associated with different seasons from previous work in this thesis, (see Chapter II Section
B).
Chi squared goodness-of-fit tests were performed on the distributions of numbers of excised
lesions to determine the significance of monthly variation. Expected values were calculated
assuming a uniform distribution of lesions would be excised each month if there were no
secular trends. Poisson regression models were used to consider variations in the rates of
malignant and potentially malignant lesions over individual months, and separately over time
periods summarised as ‘campaign’ and ‘non-campaign’, or as ‘Summer’ and ‘non-Summer’
periods. Non-parametric Kruskall-Wallis and Mann-Whitney tests considered differences in
median thickness of melanomas over time. We assumed that the effect of a campaign lasted
only as long as the campaign because the campaigns were long (over five, and two months,
respectively) and any estimates of the period of a carry-over of effect would have been
arbitrary.
Results
While there was some suggestion that pooling months into the campaign and non-campaign
periods resulted in loss of information about the variation in lesions by month (p = 0.074 for
the information lost in comparing a model by month and a model by period), the main
analytical aim was to consider seasonal and campaign effects.
During the two-and-a-half year study period 3 221 melanocytic lesions were excised, of
which 198 (6%) were either malignant (145, 4%), or potentially malignant (53, 2%).
Distributions of Level of the 145 melanomas have been described also, above, (see within
Table IV.22 of Chapter IV). The reason for excision was known for three quarters (2 406) of
the lesions, of which 1 871 (78%) were excised to confirm or exclude malignancy. Confining
the denominator to lesions removed to exclude or confirm malignancy, 6.5% malignant, and
8.5% potentially malignant lesions, were removed outside the campaign periods, Table V.1.
— 124 —
TableV.1
Effect of the campaign periods on the proportion of lesions of different
diagnostic category excised weekly, the median extent of melanoma invasion
(mm thickness) and range, and on the proportion of lesions excised to exclude
malignancy and on patient pressure to have the lesion excised.
After
Time
Before
period
any
First
Between
campaign campaign
campaign
weeks
Total
n
55.3
1295
Second second
campaign campaig
s
21.6
732
34.7
748
a
n
8.7
187
Significance
11.0
258
melanocytic
skin lesions
n/week
All melanomas,
n
dysplastic naevi
% of
and HMFs
total
n/week
Melanomas only
n
% of
23.4
33.9
21.6
21.5
23.5
77
31
47
17
26
5.9
4.2
6.3
9.1
10.1
1.4
1.4
1.4
2.0
2.4
50
23
34
15
23
p < 0.001
p < 0.01
3.9
3.1
4.5
8.0
8.9
p < 0.001
0.9
1.1
1.0
1.7
2.1
p = 0.04
total
n/week
a
Comparing across the five periods; p refers to test for trend over time
The number of benign lesions, melanomas (all levels), and Hutchinson’s melanotic freckles
excised during the course of the study changed. The total number of melanocytic lesions per
week rose during the first (longer) campaign, then fell, but did not appear to rise during the
second campaign. In contrast the numbers of melanomas and Hutchinson’s melanotic freckles
appeared not to be influenced by the first campaign, but did rise during the second, Figure
V.1.
— 125 —
Number of all
types of
melanocytic
lesions
excised,
(benign naevi,
freckles,
dysplastic
naevi,
Hutchinson's
melanotic
freckles and
melanomas)
Periods of
public
awareness
campaigns
20
0
18
016
0
14
012
0
10
08
14
12
06
0
10
8
6
4
2
Summer
months
Number of
melanomas
level 1 and
greater
Number of
Hutchinson's
melanotic
freckles
0
Month
Figure V.1 Changes in numbers of melanocytic lesions excised each month in relation to the
summer months and public awareness campaigns
There were both campaign and season effects on the monthly variation in total lesions excised
(p = 0.006 and p < 0.001 respectively). Approximately 20% more lesions were excised during
campaign periods than during non-campaign periods (rate ratio 1.24, 95% confidence interval
(CI) 1.11, 1.37). An independent effect of similar magnitude was observed for the Summer
season (rate ratio 1.22, 95% CI 1.06, 1.40). There was no statistical evidence to suggest that
the Summer effect was any higher in campaign compared to non-campaign periods (test for
interaction, p = 0.84, total lesion excision rate ratio was 1.52 for Summer, campaign periods
relative to non-Summer, non-campaign periods).
Unadjusted for campaign effects, there was a significant effect of season on excision rates of
potentially malignant lesions (p = 0.022), being 51% higher during Summer than during nonSummer periods (rate ratio 1.51 95% CI 1.06, 2.16). However, some of this effect was due to
confounding by campaign effect. The adjusted rate ratio estimates for Summer relative to
non-Summer periods was 1.33 (0.81, 2.18) and for campaign relative to non-campaign was
1.27 (0.65, 2.48). There was no statistical evidence to suggest that the Summer effect was any
higher in campaign compared to non-campaign periods (test for interaction p = 0.964,
potentially malignant lesion excision rate ratio was 1.73 for Summer, campaign periods
relative to non-Summer, non-campaign periods).
— 126 —
In considering lesions which were excised solely due to patient pressure, there was a trend
over time of decreasing patient pressure to excise, although the period after the second
campaign was not representative of this trend (Table V.2). Doctors reported feeling
themselves under significantly less pressure from patients to excise lesions during the second
campaign period, (p< 0.05). Overall, relatively fewer excisions due to patient pressure alone
were performed during campaign periods than during non-campaign periods (p = 0.009).
Table V.2.
Table V.2
Effect of the campaign periods on the patient pressure to have the lesion
excised.
After
Before any
campaign
First
Between
campaig campaign
Second
second
campaign campaig
n
s
521
710
739
177
no pressure 1
19.4
21.0
24.4
28.8
20.1
2
14.6
20.1
16.1
16.4
23.3
3
21.3
28.5
30.0
31.6
25.2
4
25.9
18.5
18.1
16.9
17.3
excision fully a 5
18.8
12.0
11.4
6.2
14.2
Number of lesions for
n
Significance
a
254
which data available (n)
Patient pressure to excise,
as perceived by the doctor
(%)
consequence of
patient pressure
a
Comparing across the five periods, pt refers to test for trend over time
b
p = 0.023 for total campaign versus total non-campaign periods.
The reason for excision was to exclude malignancy during the second campaign
period significantly more often than in other periods including the first campaign
(p< 0.0001).
— 127 —
pt = 0.023b
TableV.3
Effect of the campaign periods on the proportion of lesions excised to exclude
malignancy.
Before
Time
any
period campaig
After
First
Between
campaig campaign
Second
second
campaig campaig
n
n
s
n
n
521
710
740
179
256
Significancea
Reason for excision (%)
Number of lesions for
pt < 0.0001b
which data available (n)
a
b
To exclude malignancy
66.4
79.3
80.1
89.9
81.3
Discomfort
16.7
8.3
8.6
4.5
7.4
Cosmetic
10.9
9.9
4.9
3.4
7.4
Other
6.0
2.5
6.4
2.2
3.9
Comparing across the five periods, pt Refers to test for trend over time
Also p<0.0001 for total campaign versus total non-campaign.
Conversely, relatively more excisions to exclude malignancy were performed during
campaign periods than during non-campaign periods (p = 0.001).
There was no significant difference between the thickness of melanomas excised during
campaign periods and non-campaign periods, (p = 0.70), (Table V.4).
Table V.4
Effect of the campaign periods on the median extent of melanoma
invasion (mm thickness) and range.
Before
Time
any
First
Between
Second
second
campaig
campaign
campaig
campaign
n
n
s
n
0.50
0.33
0.32
period campaig
median
After
0.20
0.30
thickness
p = 0.304a
(mm)
range
(mm)
Significance
0.0-11.0
0.0-7.0
0.0-6.0
— 128 —
0.0-9.0
0.0-6.0
a
Mann-Whitney test for difference in median thickness between overall campaign and non-
campaign periods, p = 0.659
Methodological problems
This study was designed for the purpose of estimating the effect of public awareness
campaigns on excisions rates: the data collection was opportunistic. The effect of season has
been difficult to separate from that of the intervention. (Indeed this was deliberate: the
interventions were timed to occur when people were more likely to be susceptible to messages
about skin cancer). If financial and ethical restraints were not an issue, we might have
designed a study to answer this question by randomising the timing of the intervention, and
delivering the campaigns for different time intervals to measure the decay of any effect with
time.
Although adjustments were made to the analysis of the data to account for the effect of season
as described, some caution must be used to generalise from these data.
Conclusions
More skin lesions were excised to exclude malignancy during a public awareness campaign,
and this effect was independent of any small seasonal effect.
The main finding is congruent with an increase in the number of patients asking general
practitioners for skin examinations, as well as the increase in the number of skin examinations
performed, demonstrated during other programs educating the public about skin cancer in
Queensland.[157]
Presumably this occurred as a side-effect of the primary prevention
program rather than as a conscious attempt to increase the numbers of early melanomas
excised. An important question is whether the net effect was beneficial, that is, whether there
was an increase in the rate of detection of early malignant or potentially malignant
melanocytic lesions. A similar public awareness campaign had no significant effect on the
odds of lesions presented to general practitioners being clinically suspicious for nonmelanocytic skin cancer as well as melanoma.[158]
While this study was not specifically designed to address this question, it demonstrated a
significant campaign-related increase in rates of total lesions excised of just over 20%. This
was associated with a corresponding but statistically insignificant rise in the rates of
potentially malignant lesions excised, suggesting that excisions of malignant or potentially
— 129 —
malignant melanocytic skin lesions did not increase significantly in relation to total excisions.
We found no evidence of an increased harvest of malignant lesions, nor a reduction in the
thickness of the melanomas excised as would be expected if melanomas were excised at an
earlier stage.
The finding that doctors felt less pressured during the campaigns was unexpected. Perhaps
increased patient anxiety about skin cancer generated by the publicity campaign may have
been shared by local doctors which would off-set any perception of pressure to excise by
patients on doctors.
Whether the campaign resulted in its primary objective of improved sun-protective behaviour
is not known. Its cost was increased by unplanned additional skin excisions for which it is
hard to demonstrate benefit. Perhaps attention should be directed formally to measuring these
effects in future skin cancer publicity campaigns.
Primary prevention as a part of general practice
Role of general practice
Nature of general practice in Australia
Australian general practice is a hybrid system lying somewhere between the extremes of a
general practice-based system (such as exists in Britain and many other North European
counties including Denmark and Sweden), and a completely open 'market' such as exists in
Germany, France, and many parts of the USA.[159] The features that characterise Australian
general practice as a general practice-based system are the requirements of patients to enter
the specialist network exclusively through general practitioners, and the recognition that GPs
are central to the non-hospital care (especially by specialist and hospital-based medical
services), and the remuneration system that makes every Australian eligible for Medicare
rebates for general practice services. The most important 'free-market' characteristic of
Australian general practice is its fee-for-service form of payment for GPs, and the fact that
payment for services is 'uncapped' (meaning that there is no budgetary limitation of
expenditure on general practice payments).
— 130 —
Introduction to primary prevention for skin cancer in general practice
Public awareness campaigns have several problems with respect to reducing the harm from
skin cancer. The previous part of this chapter describes the possible harm that such campaigns
might be generating that should be measured in future campaigns so that the cost-benefit can
be estimated to decide if the balance is correct.
Attention will now be brought to bear on the possible contribution of general practice on
preventive measures for skin cancer.
Primary prevention within general practice:
General practice has become one of the main avenues for the delivery of preventive medicine
during the last 20 years. Moves in this direction were condensed in a very influential and
thoughtful paper.[160] The essential message was firstly that preventive medicine is one of
the four areas of responsibility for general practitioners in the consultation (the others being:a) dealing with the patient's primary complaint; b) addressing other health problems; and c)
ensuring that the patient had appropriate access to health care). Secondly that GPs should be
able to incorporate preventive medicine into the consultation as part of all the other
responsibilities. This notion has been called 'opportunistic' health promotion and disease
prevention, the term being used to convey the opportunistic manner in which GPs can bring in
health promoting and disease preventing activities into the consultation when they may not
have been in the patient's mind when arranging to see the doctor. There are particular
advantages of this way of delivering healthy messages:Patients are usually in a receptive frame of mind to receive any health promoting
message (because they are in the act of seeking health care);
The message can be delivered personally to each patient in relation to specific
health problems so that they will feel relevant.
Thinking in this regard may have been influenced by some successful results in the area of
smoking prevention. A randomised trial was undertaken that showed that a very simple
intervention (consisting of the doctor establishing which patients smoked; admonishing them
personally for smoking in relation to any individual health problems, and providing a brief
leaflet that recommended stopping) resulted in a small (4% overall) increase in the number
who were able to successfully stop smoking one year later.[161] The health benefits of such
an intervention have been calculated and found to be large.[162] The reason for describing in
a little detail this example is that it demonstrates the theoretical framework for providing
primary prevention in general practice rather than from wholesale messages to the community.
— 131 —
Skin cancer prevention: estimates of the possible benefits
Problems of primary prevention of skin cancer from general practice
There are several problems associated with delivering a simple primary preventive message
from primary care:The message should be evidence-based.
The two principal guidelines for the determination for preventive guidelines in this area comes
from documents produced by the Royal Australian College of General Practitioners[163] and
the National Health and Medical Research Committee. The latter has spent considerable effort
in establishing the evidence for different preventive activities for clinicians, based on the
evidence as produced by experts in the field.[164] The idea is based on a Canadian project for
the same purpose[165] and repeated by the United States Government.[166] The NHMRC
document has a chapter on skin cancer prevention.[167] It describes the evidence and
concludes that all patients should be advised of the hazards of excessive exposure to sunlight
by clinicians. This should be especially directed to children and adolescents. There is no
evidence for screening patients for skin cancer (secondary prevention), and except in
exceptionally high risk patients, this is not recommended routinely.
The RACGP 'Red Book' on preventive activities[163] has similar recommendations:p11 "Protection from sun exposure
…all patients should be informed regularly about the value of protection of the
skin from solar radiation…"
and p24 "…insufficient evidence of the accuracy of skin self-examination or of
compliance following counseling by the general practitioner" (with references to the
Canadian and US Preventive Task Force books[165] [166])
Both sets of guidelines are widely available. Perhaps, the RACGP document (which although
used evidence from a draft of the NHMRC document) was produced slightly earlier, and is
much shorter and more accessible to busy practising GPs, is more widely distributed.
— 132 —
GPs are remiss in opportunistic preventive activities
There is wealth of data to suggest that GPs are sub-optimal in their opportunistic preventive
activities.[168-175] In particular a study of the preventive activities concluded that GPs were
particularly poor at intervening in skin cancer screening because only 5% of patients attending
their GP in Queensland at risk for skin cancer (66% of men and 70% of women) were
screened for it.[171] However it must be admitted that the source used for this criterion was
not evidence-based. Using the evidence-based guidelines described above[165] [166] [163]
(not available at the time of publication), this intervention would not have been recommended.
It is not clear what the advice should be
One of the mainstays of sun-protection is the use of sun cream. These act by filtering the sun's
ultraviolet rays and converting them into longer wavelength or reflecting them out of the
tissue. Powerful creams achieve a protection called Sun Protection Factor (SPF) of 15,
meaning that the cream delays the time to erythema in sunlight in humans by 15 times.
Implicit in the use of sun-creams against skin cancer is the notion that 15 times the time to
erythema is equivalent to the same order of protection against sun cancer. This has not been
established. An evidence-based review suggests that sun creams should not be relied upon for
protection against sun cancer.[176] Therefore it must be assumed that advice should be given
about providing ancillary advice — 'Slip, Slop and Slap' (meaning slip on sun-opaque
clothing, such as long-sleeve shirts; slop on a hat with a brim wide enough to shade the face
and neck; as well as slop on sun cream) and in addition tell people to avoid going outside at
the time of day when the incident rays of ultraviolet are strongest (most vertical, so that least
scattering through the atmosphere occurs and most the rays are most closely packed).
There may be pragmatic obstacles
During a consultation during which a GP was to propose opportunistic screening for skin
cancer, presumably the GP would have to ask the patient to disrobe for an examination of the
skin naevi (and for other evidence of skin cancer if NMSC were to be included in the
examination). Any lesions that looked suspicious would be either recorded for follow-up,
referred for an opinion and management, or excised. The basis for deciding this might be
based on either the Glasgow seven-point plan[177] or the ABCD mnemonic.[91] This process
might take as long (if not longer) than quite complicated preventive manoeuvers such as
— 133 —
cervical cytology screening (because although in contrast the only equipment required is a
good light and magnification, more clothes must be removed and a greater area examined).
Moreover the numbers of naevi may prove to be daunting from a GP’s point of view. Let us
assume for the point of argument that a GP was able to screen as many as 20% of the patients
attending. This would constitute 24 patients a week multiplied by 52 weeks a year multiplied
by 20 naevi per person (to take a conservative estimate form the estimates outlined in D. 2. iii
in Chapter I), or 24 960 naevi a year. This represents a considerable number of decisions
about each lesion. It must be remembered that every benign naevus may be indistinguishable
from an 'early' melanoma. To ask a GP to accept this burden may be unreasonable. To make a
suitable decision is every case when the probability of a melanoma being present is
vanishingly small may be counter-productive.
Special advantages of primary prevention of skin cancer from general practice
General reasons
General reasons have been outlined above.
Avoiding patients who might be harmed
An ethical dilemma was outlined above whereby patients who are protected by a tan, (such as
those constantly exposed to sunlight by their occupation) might be harmed by being persuaded
to avoid a tan. Such a wholesale message might be modified by individual advice to patients
during opportunistic prevention from general practice.
Selecting patients who will benefit especially
People have been made aware of the dangers of the sun by public awareness campaigns.[178,
179] Perhaps in consequence, there is increasing evidence that the population is keeping out
of the sunlight more now than in the past.[180] For example a study of fashion magazines
over a decade showed that the presence and depth of a tan became less desirable
characteristics.[181]
However the effect is not uniform across all populations. An observational study of 85
children at the beach in the USA showed that the reasons why those that did not have
sunscreen applied (40) was related not to their skin type, past education, or child's age, but to
the parents' previous experience of a child having been painfully sunburnt.[182] Moreover,
— 134 —
children are the group who still do not elect to protect themselves from the sun according to
an observational study of over 3 000 school children in Australia.[183] A similar descriptive
study among older Australian children at school showed that the reasons they did not employ
sun protection (including but not restricted to sunscreen) was because of the desire to look
tanned, concern about peer pressure, and specific problems related to using clothes that felt
hot, and pragmatic issues related to using sunscreen cream.[184]
It appears that children, as described in Chapter I, form the most important group at special
risk from sunlight. Therefore keeping them away from the dangers of sunlight should provide
most benefit. This provides an imperative to ensure that children should be protected against
solar radiation above all other patients. Such sunlight-vulnerable stages of people's life stages
might be targeted in general practice, something that may be more difficult to achieve as
effectively in wholesale public campaigns.
Conclusions
This chapter has shown that there is indeed a role for public health interventions to encourage
the community to avoid solar radiation, and this is likely to reduce the community's incidence
of both NMSC and melanoma. There are problems with this approach. The balance between
harm and benefit has not been well defined. Data are presented that show the effects of
primary prevention interventions might have far-reaching and unexpected costs. There is a
theoretical concern that some individuals within the community might be harmed by such a
wholesale approach.
The role of general practice in primary prevention is potentially very high. It might avoid
some of the ethical concerns, and better direct attention towards people for whom there would
be highest return for preventive effort. There appears to be very little attention on this aspect
of prevention, and it is not possible to assess the extent to which general practice is rising to
meet this challenge in Australia.
— 135 —
Chapter VI
Conclusions
VI.A Workload considerations
Skin cancer is clearly an important part of general practice. NMSC is important because it so
common, and melanoma because of the vast numbers of naevi that pose diagnostic confusion.
Skin cancer is particularly interesting because it is one of the groups of problems that can be
managed almost wholly within the discipline without recourse to referral. Although advanced
and serious skin cancers will be referred, and those with advanced disease will need
considerable effort from a wide range of health workers, the vast majority of reasons for
people to talk to their doctors about skin cancer will require little outside assistance. This
emphasises the importance of good clinical management in general practice. It also
emphasises the fact that interventions designed to improve the care of skin cancer
management need to be aimed at general practice.
Since the critical area of skin cancer management is diagnosis, good management seems to
focus on this aspect of management. This is especially true for melanoma, where the presence
of a few dangerous and potentially fatal malignancies among a huge number of naevi in the
community poses a source of anxiety not only for doctors, but also people in the community at
large. Therefore it seems that there is potential to address this area. Particularly as, although
there are suggestions from the literature about how clinical diagnosis might be improved or
enhanced, there have been few attempts at testing out any ideas. This is taken further.
VI.B
The dissonance between excision patterns and the epidemiology of melanoma
The emergence of the dissonance between the workload distribution across age and sex, and
what might be expected from the risks posed by skin cancer is interesting. It suggests that
there might be potential to improve clinical performance among GPs. This dissonance has
been confirmed for naevus management in widely disparate study designs: not only the
Australian Morbidity and Therapeutics Study (Chapter II B), the Australian Sentinel Practice
Research Network (Chapter II C), the series of lesions submitted in Queensland (Chapter III),
but also in the control arm of the Naevus Management Study (Chapter IV). It seems likely to
represent a real phenomenon.
— 136 —
VI.C Patient pressure to excise
The emergence of the phenomenon of patient pressure is important. It has been explored in an
extremely applied manner. That is, little validation of whether it is real has been undertaken. It
may be that the experience lies mainly in the minds of the clinicians who describe it. This
matters little in the context of managing skin cancer, because it is what the clinicians perceive
as their patients’ concerns about the lesion that is likely to affect management.
Patient pressure to excise, as perceived by the clinicians, was found to be an important factor
on excision. Very few excisions appeared to be free of the perception. For 13%, patient
pressure was reported to be the only reason for excision. Because this factor was likely to be
important in assisting clinicians with management of naevi, it was addressed in the
intervention part of the thesis.
VI.D Improve clinical management
The main part of the intervention focussed on the diagnostic component of the management of
naevi of the skin. It had already been demonstrated that melanoma is the most important skin
cancer, despite being less common than either of the main NMSC types. However the
ubiquitous skin naevi make detecting this a great management challenge.
Part of the workload arises from perceived concern among patients, as evidenced by the
elucidation of the patient pressure problem. Another problem lies in the lack of assistance in
recording the appearance of naevi – something that would assist doctors by enabling them to
be secure in the knowledge that a naevus that they thought looked benign was in fact behaving
like a benign lesion by not changing with time.
A solution to these problems was tested using an instant-developing camera. This presented
considerable challenges to the design of an appropriate study. Funding could only be raised
for a quasi-experiment in which the doctors of an intervention city were provided with access
to the camera. The provision of the algorithm was designed more to assist in the explanation
of the purpose of the camera, and present the notion that excision of suspicious lesions
represented one option of a decision tree. This makes the option of watching and waiting a
suspicious naevus more attractive, particularly with a camera to record the appearance at one
point in time, and provide an obvious datum point not only for the clinician but also for the
— 137 —
patient whose concerns (expressed as patient pressure) can be better allayed. The results of the
trial suggest that the intervention (and it must be assumed that the algorithm as well as the
camera might have been conjointly responsible) resulted in a reduction in the number of
benign lesions excised.
The fact that the rate of melanomas excised actually increased (if not significantly) while the
benign lesions decreased suggests that the enhanced diagnostic process might tend to increase
sensitivity as well increase specificity. Such interventions are rare in medicine. Usually an
increase in sensitivity is accompanied by a decrease in specificity: detecting more diseases
usually comes at the cost of labeling more non-diseases as diseases. This suggests that some
important new process is at operation here. The diagnostic process has not simply moved the
target point further along a receiver-operator curve.
Unfortunately the methodology is not beyond criticism. The fact that the unit of
randomisation was at the city level means that the observed change in the Intervention City
might be attributable to some other unmeasured event that only affected that city. The
Intervention City had an excision of skin naevi profile along age and sex factors that better fits
the ideal according to melanoma epidemiology patterns. This fits better with the intervention
being responsible for the observed effect than some extraneous phenomenon. The patientpressure changes were more difficult to interpret.
A group of researchers (among whom I am numbered) has decided to redress this by obtaining
funding to re-run the experiment with units of randomisation at the general practice level in
Perth (far from the intervention site). This leads the methodology into another area of danger.
The risk of contamination (that is the intervention effect ‘leaking’ from intervention to control
practices by either the control practice GPs hearing of the nature of the study, or patients
hearing informally about alternative methods of managing skin ‘moles’) is more likely. This
would tend to decrease any intervention effect. This study is on going.
In the meantime the best available evidence suggests that use of a camera and algorithm has
the potential to improve diagnostic performance in the management of skin moles. There is
better evidence for this than most diagnostic aids lying about the typical GP’s surgery.
VI.E Primary Prevention
To return to NMSC as well melanoma skin cancer, it remains for the issue of primary
prevention to be addressed. Employing sun exposure avoidance measures to prevent the
— 138 —
problem is a direction that has intrinsic attractiveness as outlined in the literature review.
However there are theoretical difficulties. For one of these there was evidence from the data
collected in the Control City of the Naevus Management Study. Public awareness campaigns
appear to result in unexpected and unplanned effects on excision patterns. The fact that these
extra excisions generated by the public awareness campaigns resulted in no detectable benefit
to the population is a cause for concern because the cost of the extra excisions must have been
substantial. Moreover the excisions may represent only the tip of an iceberg of other
consultations for which no excisions was made.
Speculation at this point suggests that there might be a role for general practice in primary
prevention. GPs targeting patients at special risk (those with many naevi, those with very fair
skin, and all babies and small children) might be a new direction. However this would require
a new body of work.
— 139 —
References
1
Washington CV. Chapter 324. Skin cancer. In: Isselbacher KJ, Braunwald E, Wilson
JD, Matin JB, Fauci AS, et al, eds. Harrison's Principles of internal medicine. New
York: McGraw-Hill Inc. 1994:1866-7.
2
Emmett AJJ, O'Rourke MGE. Malignant skin tumours. Churchill Livingstone,
Edinburgh, 1982.
3
Cotran RS, Kumar V, Collins T. Robbins pathologic basis of disease. WB Saunders
Company, Philadelphia, 1999.
4
Fry J, Sandler G. Common diseases. Their nature, prevalence and care. Kluwer
Academic, Dordrecht, Netherlands, 1993.
5
Giles GG, Marks R, Foley P. Incidence of non-melanocytic skin cancer treated in
Australia. BMJ 1988;296:13-17.
6
Marks R, Staples M, Giles GG. Trends in non-melanocytic skin cancer treated in
Australia: the second national survey. Int J Cancer 1993;53:585-590.
7
Stenbeck KD, Balanda KP, Williams MJ, Ring IT, et al. Patterns of treated nonmelanoma skin cancer in Queensland — the region with the highest incidence in the
world. Med J Aust 1990;151:511-515.
8
Marks R, Jolley D, Dorevitch AP, Selwood TS. The incidence of non-melanotic skin
cancers in an Australian population: results of a five year-prospective study. Med J Aust
1989;150:475-8.
9
Harris TJ. Squamous cell carcinoma. In: Emmett AJJ, O'Rourke MGE, eds. Malignant
skin tumours. Edinburgh: Churchill Livingstone. 1982:66-82.
10
Emmett AJJ. Surgical treatment of basal cell carcinoma. In: Emmett AJJ, O'Rourke
MGE, eds. Malignant skin tumours. Edinburgh: Churchill Livingstone. 1982:59-66.
11
Bridges-Webb C, Britt H, Miles DA, Neary S, Charles J, Traynor V. Morbidity and
treatment in general practice in Australia 1990-1991. Med J Aust 1992;157:S1-S56.
12
Armstrong BK. The epidemiology and prevention of cancer in Australia. Aust NZ J
Surg 1988;58:179-187.
13
Kahn HS, Tatham LM, Patel AV, Thun MJ, Heath CW, Jr. Increased cancer mortality
following a history of nonmelanoma skin cancer. JAMA 1998;280:910-2.
14
Weinstock MA, Bogaars HA, Ashley M, Litle V, Bilodeau E, Kimmel S. Nonmelanoma
skin cancer mortality. A population-based study. Arch-Dermatol 1991;127:1194-7.
15
Armstrong BK. Epidemiology of malignant melanoma: intermittant or total
accumulated exposure to the sun? J Dermalol Surg Oncol 1988;14:835-49.
16
Milton GW. Care of the dying patient. In: Balch CM, Houghton AN, Milton GW, Sober
AJ, Soong S-J, eds. Cutaneous melanoma. Philidelphia: JB Lippincott. 1992:560-566.
— 140 —
17
Grin-Jorgensen CM, Rigel DS, Friedman RJ. 3. The worldwide incidence of malignant
melanoma. In: Balch CM, Houghton AN, Milton GW, Sober AJ, Soong S-J, eds.
Cutaneous melanoma. Philadelphia: Lipincott. 1992:27-39.
18
Hennekens CH, Buring JE. Epidemiology in medicine. 383. Little, Brown & Co,
Boston, 1987.
19
Green A. Incidence and reporting of cutaneous melanoma in Queensland. Aust J
Dermatol 1982;23:105-9.
20
Giles GG, Armstrong BK, Burton RC, Staples MP, Thursfield VJ. Has mortality from
melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. BMJ
1996;312:1121-1125.
21
Melia J. Early detection of cutaneous malignant melanoma in Britain. Int J Epidemiol
1995;24 (Suppl 1):S39-S44.
22
McCarthy WH, Martyn AL, Roberts G, Dobson AJ. Melanoma in New South Wales
1970-1976. Confirmation of increased incidence. Med J Aust 1980;2:137-40.
23
Bonett A, Roder D, Esterman A. Melanoma case survival rates in South Australia by
histological type, thickness and level of tumour at diagnosis. Med J Aust 1986;144:6802.
24
Cooke K, McNoe B, Spears G. General practice consultations involving pigmented
naevi presented for assessment of malignancy. NZ Med J 1993;106:493-5.
25
Clark W, From l, Bernandino E, Mihm M. The histogenesis and biologic behaviour of
primary human malignant melanoma of the skin. Cancer Res 1969;29:705-27.
26
Kerl H, Hödl S, Stettner H. Acral lentiginous melanoma. In: Ackerman A, eds. 12.
Pathology of malignant melanoma. New York: Masson. 1981:217-42.
27
Balch CM, Cascinelli N, Drzewiecki KT, Eldh J, MacKie RM, McCarthy WH, et al. 15.
A comparison of prognostic factors worldwide. In: Balch C, Houghton A, Milton G,
Sober A, Soong S-J, eds. Cutaneous melanoma. Philadelphia: JB Lipincott. 1992:18899.
28
Davis NC. Malignant melanoma. Clinical presentation and differential diagnosis. In:
Emmett AJJ, O'Rourke MGE, eds. Malignant skin tumours. Edinburgh: Churchill
Livingstone. 1982:107-16.
29
Koh HK. Cutaneous melanoma. New Engl J Med 1991;325:171-182.
30
Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of
cutaneous melanoma. Annals Surgery 1970;172:902-908.
31
Coleman WP, Gately LE, Krementz AB, Reed RJ, Krementz ET. Nevi, lentigines, and
melanomas in blacks. Arch Dermatol 1980;116:548-551.
32
Armstrong BK, English DR. 2. Epidemiologic studies. In: Balch C, Houghton A, Milton
G, Sober A, Soong S-J, eds. Cutaneous melanoma. Philadelphia: JB Lippincott.
1992:11-26.
— 141 —
33
Swerdlow A, English J, MacKie R, O'Doherty C, Hunter J, Clark J, et al. Benign
melanocytic naevi as a risk factor for malignant melanoma. BMJ 1986;292:1555-1559.
34
Thörn M, Pontén F, Johansson A-M, Bergström R. Rapid increase in diagnosis of
cutaneous melanoma in situ in Sweden, 1968-1992. Cancer Detect Control
1998;22:430-37.
35
Deleo VA. Prevention of skin cancer. J Dermatol Surg Oncol 1988;14:902-6.
36
Elwood JM, Gallagher RP, Hill GB, Spinelli JJ, Pearson JCG, Threlfall W.
Pigmentation and skin reaction to sun as risk factors for cutaneous melanoma: Western
Canada Melanoma Study. BMJ 1984;288:99-102.
37
Gilbody JS, Aitken J, Green A. What causes basal cell carcinoma to be the commonest
cancer? Aust J Public Health 1994;18:218-21.
38
Rhodes AR, Weinstock MA, Fitzpatrick TB, Mihm MC, Sober AJ. Risk factors for
cutaneous melanoma. A practical method of recognising predisposed individuals. JAMA
1987;258:3146-54.
39
Evans RD, Kopf AW, Lew RA, Rigel DS, Bart RS, Friedman RJ, et al. Risk factors for
the development of malignant melanoma—1: review of case-control studies. J Dermatol
Surg Oncol 1988;14:393-408.
40
MacKie RM, Freudenberger T, Aitchison TC. Personal risk-factor chart for cutaneous
melanoma. Lancet 1989;2:487-90.
41
Gellin GA, Kopf AW, Garfinkle L. Malignant melanoma. A controlled study of possible
associated factors. Arch Dermatol 1969;99:43-8.
42
Lee JAH, Strickland D. Malignant melanoma: social status and outdoor work. Br J
Cancer 1980;41:757-63.
43
Kricker A, Armstrong BK, English DR. Sun exposure and non-melanocytic skin cancer.
Cancer Causes and Control 1995;5:367-92.
44
Bliss JM, Ford D, Swerdlow AJ, Armstrong BK, Cristofolini M, Elwood JM, et al. Risk
of cutaneous melanoma associated with pigmentation characteristics and freckling:
systematic overview of 10 case-control studies. The International Melanoma Analysis
Group (IMAGE). Int J Cancer 1995;62:367-76.
45
English DR, Armstrong BK, Kricker A, Winter MG, Heenan PJ, Randell PL. Casecontrol study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer
1998;77:347-53.
46
English DR, Armstrong BK. Identifying people at high risk of cutaneous malignant
melanoma: results from a case-control study in Western Australia. BMJ 1988;296:12858.
47
Kricker A, Armstrong BK, English DR, Heenan PJ. Pigmentary and cutaneous risk
factors for non-melanocytic skin cancer—a case-control study. Int J Cancer
1991;48:650-62.
— 142 —
48
Garbe C, Kruger S, Stadler R, Guggenmoos Holzmann I, Orfanos CE. Markers and
relative risk in a German population for developing malignant melanoma. Int J
Dermatol 1989;28:517-23.
49
Holman CD, Armstrong BK. Cutaneous malignant melanoma and indicators of total
accumulated exposure to the sun: an analysis separating histogenetic types. J Natl
Cancer Inst 1984;73:75-82.
50
Armstrong BK, de Klerk NH, Holman CD. Etiology of common acquired melanocytic
nevi: constitutional variables, sun exposure, and diet. J Natl Cancer Inst 1986;77:32935.
51
Augustsson A, Stiener U, Rosdahl I, Suurkula M. Common and dysplastic naevi as risk
factors for cutaneous malignant melanoma in a Swedish population. Acta Derm
Venereol (Stockh) 1990;71:518-524.
52
Sober AJ, Koh HK. Chapter 325. Melanoma and other pigmented skin lesions. In:
Isselbacher KJ, Braunwald E, Wilson JD, Matin JB, Fauci AS, et al, eds. Harrison's
Principles of internal medicine. New York: McGraw-Hill Inc. 1994:1867-71.
53
Marks R, Jolly D, Lectsas S, Foley P. The role of childhood exposure to sunlight in the
development of solar keratoses and non-melanotic skin cancer. Med J Aust
1990;152:62-6.
54
Kricker A, Armstrong BK, English DR, Heenan PJ. A dose-response curve for sun
exposure and basal call carcinoma. Int J Cancer 1995;60:482-8.
55
Osterlind A, Tucker MA, Stone BJ, Jensen OM. The Danish case-control study of
cutaneous malignant melanoma. II. Importance of UV-light exposure. Int J Cancer
1988;42:319-24.
56
Elwood JM, Gallagher RP, Davison J, Hill GB. Sunburn, suntan and the risk of
cutaneous malignant melanoma - The western Canada melanoma study. Brit J Cancer
1985;51:543-549.
57
Kricker A, English DR, Randell PL, Heenan PJ, Clay CD, Delaney TA, et al. Skin
cancer in Geraldton, Western Australia: a survey of incidence and prevalence. Med J
Aust 1990;152:399-407.
58
Holman CD, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant
melanoma to individual sunlight-exposure habits. J Natl Cancer Inst 1986;76:403-14.
59
Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies.
Int J Cancer 1997;73:198-203.
60
Autier P, Dore JF, Schifflers E, Cesarini JP, Bollaerts A, Koelmel KF, et al. Melanoma
and use of sunscreens: an EORTC case-control study in Germany, Belgium and France.
Int J Cancer 1995;61:749-55.
61
Westerdahl J, Olsson H, Masback A, Ingvar C, Jonsson N. Is the use of sunscreens a
risk factor for malignant melanoma? Melanoma Research 1995;5:59-65.
— 143 —
62
Hill AB. The environment and disease: association or causation? Proc Roy Soc Med
1965;58:295-9.
63
Hennekens CH, Buring JE. Chapter 3. Statistical association and cause-effect
relationships. In: Mayrent SL, eds. Epidemiology in medicine. Boston: Little, Brown &
Co. 1987:30-53.
64
Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen
use. N Engl J Med 1993;329:1147-51.
65
Weinstock MA, Colditz GA, WIllett WC, Stampfer MJ, Bronstein BR, Mihm MC, et al.
Melanoma and the sun: the effect of swimsuits and a 'healthy' tan on the risk of
nonfamilial malignant melanoma in women. Am J Epidemiol 1991;134:462-70.
66
Green A. A theory of site distribution of melanomas: Queensland, Australia. Cancer
Causes Control 1992;3:513-6.
67
Koh HK, Kligler BE, Lew RA. Yearly review. Sunlight and cutaneous malignant
melanoma: evidence for and against causation. Photochemistry and photobiology
1990;51:765-79.
68
Marks R, Whiteman D. Sunburn and melanoma: how strong is the evidence? BMJ
1994;308:75-6.
69
Swerdlow AJ, English J, MacKie RM, O'Doherty JAA, Clark J. Benign naevi associated
with high risk of melanoma [letter]. Lancet 1984;2:168.
70
Grob JJ, Gouvernet J, Aymar D, Mostaque A, Romano MP, Collet AM, et al. Count of
benign melanocytic naevi as a major indicator of risk for nonfamilial nodular and
superficial spreading melanoma. Cancer 1990;66:387-395.
71
Clark WHJ, Reimer RR, Greene M, Ainsworth AM, Mastrangelo MJ. Origin of familial
melanomas from heretable melanocytic lesions. “The B-K Syndrome”. Arch Dermatol
1978;114:732-8.
72
NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA
1992;268:1314-9.
73
Ford D, Bliss JM, Swerdlow AJ, Armstrong BK, Franceschi S, Green A, et al. Risk of
cutaneous melanoma associated with a family history of the disease. The International
Melanoma Analysis Group (IMAGE). Int J Cancer 1995;62:377-81.
74
Clemente C, Cochrane AJ, Elder DE, et al. Histopathic diagnosis of dysplastic nevi:
concordance among pathologists convened by the World Health Organisation
Melanoma Programme. Hum Pathol 1991;22:313-319.
75
Elder DE, Greene MH, Bondi E, Clark WHJ. 11 Acquired melanocytic nevi and
melanoma. The dysplastic nevus syndrome. In: Ackerman A, eds. Pathology of
malignant melanoma. New York: Masson. 1981:185-215.
— 144 —
76
Carr BR, Wilson JD. Chapter 340. Disorders of the ovary and female reproductive tract.
In: Isselbacher KJ, Braunwald E, Wilson JD, Matin JB, Fauci AS, et al, eds. Harrison's
Principles of internal medicine. New York: McGraw-Hill Inc. 1994:2012-36.
77
Mayer RJ. Chapter 257. Tumours of the large and small intestine. In: Isselbacher KJ,
Braunwald E, Wilson JD, Matin JB, Fauci AS, et al, eds. Harrison's Principles of
internal medicine. New York: McGraw-Hill Inc. 1994:1424-31.
78
Marks R, Dorevitch AP, Mason G. Do all melanomas come from "moles"? A study of
the histological association between melanocytic naevi and melanoma. Australas J
Dermatol 1990;31:77-80.
79
Skender Kalnenas TM, English DR, Heenan PJ. Benign melanocytic lesions: risk
markers or precursors of cutaneous melanoma? J Am Acad Dermatol 1995;33:1000-7.
80
Greene MH, Clarke WHJ, Tucker MA, Elder DE, Kraemer KH, Guerry D, et al.
Acquired precursors of cutaneous malignant melanoma. The familial dysplastic nevus
syndrome. New Engl J Med 1985;312:91-7.
81
Shoenfeld Y, Mor R, Weinberger A, Avidor I, Pinkhas J. Diagonal ear lobe crease and
coronary risk factors. J Am Geriatr Soc 1980;28:184-7.
82
Lund HZ, Stobbe GD. The natural history of the pigmented nevus factors of age and
anatomic location. Am J Pathol 1949;25:1117-1147.
83
MacKie RM, English J, Aitchison TC, Fitzsimons CP, Wilson P. The number and
distribution of benign pigmented moles (melanocytic naevi) in a healthy British
population. Br J Dermatol 1985;113:167-74.
84
Coombs BD, Sharples KJ, Cooke KR, Skegg DCG, Elwood JM. Variation and
covariates of the number of benign nevi in adolescents. Am J Epidemiol 1992;136:344355.
85
English DR, Armstrong BK. Melanocytic nevi in children. 1 Anatomic sites and
demographic and host factors. Am J Epidemiol 1994;139:390-401.
86
Black HS, Thornby JI, Wolf JE, Goldberg LH, Herd JA, Rosen T, et al. Evidence that a
low-fat diet reduces the occurrence of non-melanoma skin cancer. Int J Cancer
1995;62:165-169.
87
Bain C, Green A, Siskind V, Alexander J, Harvey P. Diet and melanoma; an exploratory
case-control study. Ann Epidemiol 1993;3:235-238.
88
Osterlind A, Tucker MA, Stone BJ, Jensen OM. The Danish case-control study of
cutaneous malignant melanoma. IV. No association with nutritional factors, alcohol,
smoking or hair dyes. Int J Cancer 1988;42:825-8.
89
Del Mar C. Slip, slop, slap and wrap. Should we do more to prevent skin cancer? Med J
Aust 1995;163:511-2.
90
MacKie RM. Clinical recognition of early invasive malignant melanoma. BMJ
1990;301:1005-6.
— 145 —
91
McGovern TW, Litaker MS. Clinical predictors of malignant pigmented lesions. A
comparison of the Glasgow seven-point checklist and the American Cancer Society's
ABCDs of pigmented lesions. J Dermatol Surg Oncol 1992;18:22-6.
92
Witheiler DD, Cockerell CJ. Histologic features and sensitivity of diagnosis of
clinically unsuspected cutaneous melanoma. Am J Dermatopathol 1991;13:551-6.
93
Andersen WK, Silvers DN. 'Melanoma? It can't be melanoma!' A subset of melanomas
that defies clinical recognition. JAMA 1991;266:3463-5.
94
Higgins EM, Hall P, Todd P, Murthi R, Du Vivier AW. The application of the sevenpoint check-list in the assessment of benign pigmented lesions. Clin Exp Dermatol
1992;17:313-5.
95
DeCoste SD, Stern RS. Diagnosis and treatment of nevomelanocytic lesions of the skin.
A community-based study. Arch Dermatol 1993;129:57-62.
96
Fernando SSE. Incidence of melanoma in surgically removed pigmented lesions.
Australas J Dermatol 1987;28:126-128.
97
Bosch MMC, Boon M. Profile of the malignant melanoma excised in general practice.
Br J Dermatol 1994;130:57-61.
98
Herd RM, Hunter JA, McLaren KM, Chetty U, Watson AC, Gollock JM. Excision
biopsy of malignant melanoma by general practitioners in south east Scotland 1982-91.
BMJ 1992;305:1476-8.
99
Koh HK, Miller DR, Geller AC, Clapp RW, Mercer MB, Lew RA. Who discovers
melanoma? Patterns from a population-based survey. J Am Acad Dermatol
1992;26:914-9.
100 Hennrikus D, Girgis A, Redman S, Sanson-Fisher RW. A community study of delay in
presenting with signs of melanoma to medical practitioners. Arch Dermatol
1991;127:356-61.
101 Doherty VR, MacKie RM. Reasons for poor prognosis in British patients with
cutaneous malignant melanoma. BMJ 1986;292:987-9.
102 Krige JE, Isaacs S, Hudson DA, King HS, Strover RM, Johnson CA. Delay in the
diagnosis of cutaneous malignant melanoma. A prospective study in 250 patients.
Cancer 1991;68:2064-8.
103 Cassileth BR, Clark WH, Lusk EJ, Frederick BE, Thompson CJ, Walsh WP. How well
do physicians recognise melanoma and other problem lesions? J Am Acad Dermatol
1986;14:555-60.
104 Ramsay D, Benimoff A. The ability of primary care physicians to recognize the
common dermatoses. Arch Dermatol 1981;117:620-22.
105 Kelly JW, Crutcher WA, Sagebiel RW. Clinical diagnosis of dysplastic melanocytic
nevi. A clinicopthologic correlation. J Am Acad Dermatol 1986;14:1044-52.
— 146 —
106 Green A, Leslie D, Weedon D. Diagnosis of skin cancer in the general population:
clinical accuracy in the Nambour survey. Med J Aust 1988;148:447-50.
107 Girgis A, Sanson-Fisher RW, Howe C, Raffan B. A skin cancer training programme:
evaluation of a postgraduate training for family doctors. Medical Education
1995;29:364-371.
108 Paine SL, Cockburn J, Noy SM, Marks R. Early detection of skin cancer. Knowledge,
perceptions and practices of general practitioners in Victoria. Med J Aust 1994;161:188195.
109 Grin CM, Kopf AW, Welkovich B, Bart RS, Levenstein MJ. Accuracy in the clinical
diagnosis of malignant melanoma. Arch Dermatol 1990;126:763-6.
110 Curley RK, Cook MG, Fallowfield ME, Marsden RA. Accuracy in clinically evaluating
pigmented lesions. BMJ 1989;299:16-18.
111 Davis NC. Malignant melanoma. Clinical presentation and differential diagnosis. In:
Emmett A, O'Rourke M, eds. Malignant skin tumours. Sydney: Churchill Livingston.
1991:71-80.
112 Davis NC, McLeod GR. 1. The history of melanoma from Hunter to Handley (17871907). In: Balch C, Houghton A, Milton G, Sober A, Soong S-J, eds. Cutaneous
melanoma. Philadelphia: JB Lippincott. 1992:3-11.
113 Timmons MJ. Malignant melanoma excision margins: making a choice. Lancet
1992;340:1393-5.
114 Heenan PJ, English DR, Holman CD, Armstrong BK. The effects of surgical treatment
on survival and local recurrence of cutaneous malignant melanoma. Cancer
1992;69:421-6.
115 Veronesi U, Cascinelli N, Adamus J, Balch C, Bandiera D, Barchuk A, et al. Thin stage
I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or
3 cm. N Engl J Med 1988;318:1159-62.
116 Balch CM, Urist MM, Karakousis CP, Smith TJ, Temple WJ, Drzewiecki K, et al.
Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm):
Results of a multi-institutional randomized surgical trial. Ann Surg 1993;218:262-9.
117 Ringborg U, Andersson R, Eldh J, Glaumann B, Hafstrom L, Jacobsson S, et al.
Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor
thickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group.
Cancer 1996;77:1809-14.
118 Dickinson J, Lalor E, Calcino G, Douglass J, Knight R. The supply and distribution of
general practitioners. In: Branch GP, eds. General Practice in Australia 1996. Canberra:
Commonwealth Government Publisher. 1996:25-64.
119 Australian Bureau of Statistics C. http://www.abs.gov.au/websitedbs/. 1996.
— 147 —
120 Lamberts H, Woods ME. ICPC. International classification of primary care. OUP,
Oxford, 1987.
121 Australian Bureau of Statistics. June 1987-June 1992. Estimated resident population by
sex and age. States and Territories of Australia. Commonwealth Government of
Australia. Catalogue number 3201.0. 1993.
122 Australian Sentinel Practice Research Network.
ASPREN
Annual
Report
1993.
Research and Health Promotion Unit, Royal Australian College of General
Practitioners. ISSN 1038-3069. 1994.
123 O'Toole B, Driver B, Britt H, Bridges-Webb C. Using general practitioners to measure
community morbididty. Int J Epidemiol 1991;20:1125-1132.
124 Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology, the essentials. Williams
and Williams, Baltimore, 1988.
125 Fletcher RH, Fletcher SW, Wagner EH. Chapter 7. Treatment. eds. Clinical
epidemiology, the essentials. Baltimore: Williams and Williams. 1988:129-56.
126 Green A. Changing patterns in incidence of non-melanoma skin cancer. Epithelial Cell Biol
1992;1:47-51.
127 Davis NC. Malignant melanoma: the Australian contribution. Aust N Z J Surg
1988;58:605-617.
128 MacLennan R, Green AC, McLeod GRC, Martin NG. Increasing incidence of
cutaneous melanoma in Queensland, Australia. J Natl Cancer Inst 1992;84:1427-32.
129 Brown J, Stewart M, McCCracken E, McWhinney IR, Levenstein J. The patient centred
clinical method. 2: definition and applications. Family Practice 1986;3:75-79.
130 Pendleton DA, Schofield TPC, Tate PHL, Havelock PB. The consultation; an approach
to learning and teaching. Oxford University Press, Oxford, 1984.
131 Fleming MG, Swan LS, Heenan PJ. Seasonal variation in the proliferation fraction of
Australian common nevi. Am J Dermatopath 1991;13:463-6.
132 Bain C, Colditz GA, Willett WC, Stampfer MJ, Green A, Bronstein BR, et al. Selfreports of mole counts and cutaneous malignant melanoma in women: methodological
issues and risk of disease. Am J Epidemiol 1988;127:703-712.
133 McPherson A. Women's problems in general practice. Oxford University Press, Oxford,
1987.
134 Green A, Swerdlow AJ. Epidemiology of melanocytic nevi. Epidemiological Reviews
1989;11:204-221.
135 Hancock L, Sanson-Fisher R, Redman S, Reid A, Tripodi T. Knowledge of cancer risk
reduction practices in rural towns of New South Wales. Aust N Z J Public Health
1996;20:529-37.
— 148 —
136 Del Mar C, Green A, Cooney T, Cutbush K, Lawrie S, Adkins G. Melanocytic lesions
excised from the skin: what percentage are malignant? Aust J Public Health
1994;18:221-3.
137 Queensland Cancer Register. Cancer in Queensland: incidence of malignancy 1985.
Queensland Department of Health. 1991.
138 Armstrong BK, Heenan PJ, Caruso V, Glancy RJ, Holman CDJ. Seasonal variation in
the junctional component of pigmented naevi (letter). Int J Cancer 1984;34:441-442.
139 Stern RS, Boudreaux C, Arndt KA. Diagnostic accuracy and appropriatness of care for
seborrheic keratoses. A pilot study of an approach to quality assurance for cutaneous
surgery. JAMA 1991;265:74-77.
140 Marks R, Jolley D, McCormack C, Dorevitch AP. Who removes pigmented skin
lesions? A study of the ratio of melanoma to other benign tumours removed by different
categories of physicicans in Australia in 1989 and 1994. J Am Acad Dermatol
1997;36:721-6.
141 de Dombal FT, Leaper DJ, Horrocks JC, Staniland JR, McCann AP. Human and
computer-aided diagnosis of abdominal pain: Further report with emphasis on
performance of clinicians. BMJ 1974;1:376-380.
142 Green A, MacLennan R, Youl P, Martin N. Site distribution of cutaneous melanoma in
Queensland. Int J Cancer 1993;53:232-6.
143 Weedon D, Strutton G. Malignant melanoma. Pathology. In: Emmett AJJ, O'Rourke
MGE, eds. Malignant skin tumours. Edinburgh: Churchill Livingstone. 1982:116-22.
144 Burton RC, Coates MS, Hersey P, Roberts G, Chetty MP, Chen S, et al. An analysis of
a melanoma epidemic. Int J Cancer 1993;55:765-70.
145 Bain DJ. The content of physician/patient communication in family practice. J Fam
Pract 1979;8:745-53.
146 Del Mar CB. Communicating well in general practice. Med J Aust 1994;160:367-70.
147 Fletcher RH, Fletcher SW, Wagner EH. Chapter 3. Diagnosis. eds. Clinical
epidemiology, the essentials. Baltimore: Williams and Williams. 1988:42-75.
148 Fahey T, Newton J. Conveying the benefits and risks of treatment. Br J Gen Pract
1995;45:339-41.
149 Ward J, Boyle K. General practitioners' estimates of the ideal benign-to-malignant ratio
for excised pigmented lesions [letter]. Aust J Public Health 1994;18:454-5.
150 Skrabanek P, McCormick J. Follies and fallacies in medicine. The Tarragon Press,
Glasgow, 1989.
151 Skrabenek P. The death of humane medicine and the rise of coercive healthism. The
Social Affairs Unit, Bury St Edmunds, 1994.
152 Marks R. Freckles, moles and melanoma. National Skin Cancer Awareness Week 1988.
Aust Fam Physician 1988;17:1025.
— 149 —
153 McCarthy WH, Shaw HM. Trends in the epidemiology, diagnosis and management of
melanoma. Cancer Forum 1990;14:6-10.
154 Stern RS, Weinstein MC, Baker SG. Risk reduction for nonmelanoma skin cancer with
childhood sunscreen use. Arch Dermatol 1986;122:537-45.
155 Del Mar CB, Green AC, Battistutta D. Do public media campaigns designed to increase
skin cancer awareness result in increased skin excision rates? Aust NZ J Public Health
1997;21:751-3.
156 Del Mar C. Should general practitioners embrace primary prevention rather than early
detection to prevent skin cancer mortality and morbidity? Cancer Forum 1998;22:2730.
157 Del Mar CB, Stanton WR, Gillespie AM, Lowe JB, Balanda KP. What use do people
make of physicians in checking their skin for cancer? Cancer Detect Prev 1996;20:32531.
158 Lowe JB, Balanda KP, Del Mar CB, Purdie D, Hilsdon AM. General practitioner and
patient response during a public education program to encourage skin examinations.
Med J Aust 1994;161:195-8.
159 Starfield B, Powe N, Weiner J, Stuart M, Steinwachs D, Scholle S, et al. Costs vs
quality in different types of primary care. JAMA 1994;272:1903-8.
160 Stott NCH, Davis RH. The exceptional potential in each primary care consultation. J
Roy Col Gen Pract 1979;29:201-205.
161 Russell MAH, Wilson C, Taylor C, Baker CD. Effects of general practitioner's advice
against smoking. BMJ 1979;2:231-235.
162 Copeman D, Del Mar C, Swannell R. Helping patients to stop smoking. Aust Fam Phys
1990;19:67-92.
163 Preventive Community Medicine Committee of RACGP. Guidelines for preventive
activities in general practice (4th edition). Royal Australian College of General
Practitioners, Melbourne, 1996.
164 NHMRC. Guidelines for preventive interventions in primary health care: cardiovascular
disease and cancer. Commonwealth of Australia. 2117. 1997.
165 The Canadian Task Force on the Periodic Health Examination.
Clinical
preventive
health care. Minister of Supply and Services Canada, Ottawa, 1994.
166 US Preventive Services Task Force. Guide to clinical preventive services. Williams &
Wilkins, Baltimore, 1996.
167 NHMRC. Chapter 10. Screening for skin cancer. eds. Guidelines for preventive
interventions in primary health care: cardiovascular disease and cancer. Canberra:
Commonwealth of Australia. 1997:99-115.
168 Ward JE, Gordon J, Sanson-Fisher RW. Strategies to increase preventive care in general
practice. Med J Aust 1991;154:523-531.
— 150 —
169 Mant D. Facilitating prevention in primary care. BMJ 1992;304:652-3.
170 Heywood A, Ring I, Sanson-Fisher R, Mudge P. Screening for cardiovascular disease
and risk reduction counselling behaviours of general practitioners. Prev Med
1994;23:292-301.
171 Heywood A, Ring I, Sanson-Fisher R, Mudge P. Risk prevalence and screening for
cancer by general practitioners. Prev Med 1994;23:152-9.
172 Dunn EV, Bass MJ, Williams JI, Borgiel AE, MacDonald P, Spasoff RA. Study of
relation of continuing medical education to quality of family physicians' care. J Med
Educ 1988;63:775-84.
173 Morrell DC, Evans ME, Moris RW, Roland MO. The five minute consultation: effect of
time constraint on clinical content and patient satisfaction. BMJ 1986;292:870-876.
174 Silagy C, Muir J, Coulter A, Thorogood M, Yudkin P, Roe L. Lifestyle advice in
general practice: rates recalled by patients. BMJ 1992;305:871-874.
175 Tudor Hart J. Coronary heart disease: preventable but not prevented? Br J Gen Pract
1990;40:441-443.
176 Anon. Do sunscreens prevent skin cancer? Drug and Therapeutics Bulletin 1998;36:4951.
177 MacKie RM. Malignant melanoma: a guide to early diagnosis. Pillans & Wilson,
Edinburgh, 1989.
178 Borland R, Hill D, Noy S. Being sunsmart: changes in community awareness and
reported behaviour following a primary prevention program for skin cancer control.
Behaviour Change 1990;7:126-35.
179 Borland RM, Hocking B, Godkin G, Gibbs AF, Hill DJ. The impact of a skin cancer
control education package for outdoor workers. Med J Aust 1991;154:686-688.
180 Marks R. Skin cancer control in Australia: have we made any difference? Aust J Public
Health 1994;18:127-8.
181 Chapman S, Marks R, King M. Trends in tans and skin protection in Australian fashion
magazines, 1982 through 1991. Am J Public Health 1992;82:1677-80.
182 Maducdoc DR, Wagner RF, Wagner KD. Parents' use of sunscreen on beach-going
children. Arch Dermatol 1992;128:628-629.
183 Cockburn J, Hennikus D, Scott R, Sanson-Fisher R. Adolescent use of sun-protection
measures. Med J Aust 1989;151:136-40.
184 Lowe JB, Balanda KP, Gillespie AM, Del Mar CB, Gentle AF. Sun-related attitudes and
beliefs among Queensland school children: the role of gender and age. Aust J Public
Health 1993;17:202-8.
— 151 —