Preoperative Serum Prostate-specific Antigen, Clinical Stage and Gleason Sum
as Basis for Predicting Final Pathological Stage in Japanese Patients with
Prostate Cancer
Shin Egawa, Hjdeshige Koh, Takefumi Satoh, Makoto Ohori, Toyoaki Uchida, Sadahito Kuwao
and Ken Koshiba
Departments of Urology and Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa
By logistic regression analysis and log-likelihood ratio chi-square test, the usefulness of preoperative variables (prostate specific antigen [PSA], clinical stage and biopsy Gleason sum) for predicting the final pathological stage was assessed in 77 patients with clinically resectable prostate
cancers. Pathologically, 32 (41.6%) had organ-confined disease. Extracapsular extension was found
in 41 (53.2%), seminal vesicle involvement in 30 (39.0%), positive pelvic lymph nodes in 10
(13.0%) and a positive surgical margin in 27 (35.1%). Each preoperative variable was found to
be significantly associated with the final pathological stage. Any combination of these variables
was more predictive for extraprostatic disease, compared with each individual. variable. Extraprostatic spread was found more frequently in patients with lower serum PSA in this Japanese
elderly male population compared with North American males. These preoperative variables considered in combination may provide valuable information for management decisions related to
prostate cancer. Serum PSA alone cannot reliably predict pathological stage on an individual
basis except in patients with a PSA level of 20 ng/ml or greater. The high incidence of extraprostatic spread at intermediate PSA underscores the importance of selecting an ideal cutoff
value for PSA-based screening in a Japanese male population.
(Jpn J Clin Oncol 26: 438-444, 1996)
Key words:. Prostate cancer—Pathological stage—Clinical staging—Prostate specific antigen—
Tumor grade
Introduction
The incidence of prostate cancer is presently increasing and it is now the 9th cause of male cancer
death in Japan.1"3' The incidence of this disorder
has soared from 6482 in 1988 to an estimated 9000
in 1994. Several options are available for treatment.
Radical prostatectomy is most effective and is
usually indicated when the disease is organconfined. Accurate preoperative staging is thus
paramount for the proper selection of patients for
this operation if cure or enhanced long-term survival is the primary objective. However, microscopic tumor extension beyond the capsule is found not
infrequently, and as a result, many patients with
Received: March 14, 1996
Accepted: May 20, 1996
For reprints and all correspondence: Shin Egawa, Department of Urology, Kitasato University School of Medicine,
15-1, Kitasato 1-chome, Sagamihara, Kanagawa 228
438
stage pT3 disease undergo radical prostatectomy.4'^
Thus, existing techniques for staging are often inaccurate and inadequate. Several investigators have
advocated the combined use of prostate specific antigen (PSA) level, clinical stage and biopsy Gleason
sum to improve the preoperative predictability of
the pathological stage.6"8'
The usefulness of these variables in combination
for predicting tumor extent has not yet been assessed in the Japanese elderly male population. A
given serum PSA for a Japanese male may have a
clinical meaning differing from that in a Caucasian
of the same age.9) A model for Japanese patients
should thus be established to distinguish patients
with organ-confined disease from those with more
advanced disease. The present study is the first in
Japan to compare preoperative staging data with final pathological findings in patients with prostate
cancer following radical prostatectomy.
Jpn J Clin Oncol 26(6) 1996
PREDICTION OF PATHOLOGICAL STAGE
Materials and Methods
Between January 1992 and October 1995, 87
Japanese men diagnosed as having clinically resectable prostate cancer (T1-T3N0M0) underwent radical prostatectomy at Kitasato University Hospital.
In 17 patients, the disease was discovered through
a PSA-based early detection program.9' Since 1992,
all tumors have been assigned a clinical stage according to the unified tumor node metastasis
(TNM) system at our institution.l0) Briefly, stage
Tla tumors were incidental histologic findings in
5% or less of tissue resected, stage Tib tumors
were an incidental histologic findings in more than
5% of tissue resected. Patients with positive biopsy cores and benign-feeling glands were considered
as stage Tic when sonographic findings were unremarkable for malignancy. T2a arid b were palpable tumors confined to within the prostate and
involving a portion of or the entire lobe; stage T2c
were palpable tumors confined to within the
prostate and involving both lobes; stage T3a and b
were palpable tumors extending through the prostatic capsule with unilateral or bilateral extension,
respectively; stage T3c were palpable tumors extending through the prostatic capsule and involving the
seminal vesicles. Eight of these patients underwent
preoperative hormonal manipulation. Two cases initially diagnosed as stage Tic, well differentiated
carcinoma, showed only atypical adenomatous
hyperplasia (AAH) and a moderate degree of
prostatic intraepithelial neoplasia in the surgical
specimens. A retrospective review of patient biopsy cores indicated AAH rather than invasive
tumors. These 10 cases were excluded from further
study.
Rectal examination was conducted by one of the
authors (S.E.) preoperatively, and abnormal findings such as irregularity, asymmetry and nodule
(nodularity or presence of a nodule) were recorded.
An arbitrarily chosen lower PSA cut-off value of
2.0 ng/ml is used at our institution as indication
for biopsy instead of that recommended by the
manufacturer (0 to 4.0 ng/ml).9>1112) Pretreatment
PSA, collected on an ambulatory basis prior to biopsy or other studies, was measured by either a
Dinapak® IMx PSA (Dinabot, Tokyo, 44 patients)
or an Eiken polyclonal radioimmunoassay (Eiken,
Tokyo, 33 patients).11"13' For uniformity, PSA data
were expressed as IMx PSA. Frozen serum samples
kept at -80°C were used to obtain data on IMx
PSA in 28 patients, after being stored for an average of 22.5 (range, 2-36) months. Data for the
other five patients could be obtained only by Eiken
polyclonal radioimmunoassay. Eiken PSA data were
inter-converted as recommended by Machida et al.
as follows: IMx PSA = 1.39 X Eiken PSA -1.02. 12 '
Pre- and postoperative histological diagnoses of
biopsy and surgical specimens were made by a single pathologist (S.K.). All needle biopsies were conducted with an 18- gauge automated spring-loaded
biopsy gun within 3 months before radical
prostatectomy. When no hypoechoic area could be
found, the needle was directed in such a way as to
maximize sampling of the peripheral zone as
described by Hodge et c/. u ) For suspicious
hypoechoic lesions, directed biopsy from the lesion
as well as random sextant biopsy were usually conducted. However, random sampling biopsy from
the contralateral side in addition to directed biopsy of a hypoechoic lesion was conducted in 8 patients. The number of needle cores per specimen
varied from 2 to 8 (mean 6.3). Gleason primary
and secondary patterns as well as Gleason sum
were evaluated in each biopsy specimen containing
cancer and assigned accordingly. All patients underwent pelvic lymphadenectomy followed by radical
prostatectomy. All lymphadenectomy specimens
were made into permanent sections. Radical
prostatectomy specimens were examined by whole
organ step-section techniques in all but two cases.9'
The specimens were fixed in 10% formalin and sectioned at 5-mm intervals in a plane perpendicular
to the long axis of the gland, from the prostatic
apex to tip of the seminal vesicles. Random sectioning was done in two patients and each section
was stained with hematoxylin and eosin. Tumor
grade and depth of capsular penetration were determined based on criteria specified previously.15'
Searches for, and assessment of, seminal vesicle invasion, tumor extension to surgical margin and the
presence of nodal metastasis were done. A tumor
was categorized as organ-confined if appearing
pathologically confined to the prostate and advanced if extending through the capsule.
Logistic regression analysis with log-likelihood ratio chi-squared test was carried out to define the
correlation between each preoperative variable (clinical stage, serum PSA and preoperative Gleason
sum) and each component of pathological stage.
Results
Mean subject age was 63.9 years (range 50 to 74,
median 64). Mean serum PSA for the 77 patients
was 16.3 ng/ml (range 0.8 to 136, median 7.9).
The 77 cancers were classified clinically as stages
Tla in one, Tib in three, Tic in 23, T2a in eight,
T2b in 17, T2c in nine, T3a in two, T3b in three
and T3c in 11 patients. Tumor grade was classified
preoperatively as well (Gleason sum 2-4) or moderately (Gleason sum 5 or 6) differentiated in 20
(26.0%) or 22 (28.6%) patients, respectively.
Nineteen (24.7%) and 16 (20.8%) patients had
439
EGAWA ET AL.
Table I.
Correlation of Clinical Stage with Final Pathological Findings
Final pathological findings
Clinical
stage
No. Pts.
No. (<%)
1
3
23
8
17
9
2
3
11
77
Tla
Tib
Tic
T2a
T2b
T2c
T3a
T3b
T3c
Total
(1.3)
(3.9)
(29.9)
(10.4)
(22.0)
(11.7)
(2.6)
(3.9)
(14.3)
(100.0)
PSA (ng/ml)
Mean±SD
Organ
confined
No. (%)
ECE
No. (•%)
SVI
No. (%)
Nodal inv.
No. (%)
Positive
margin
No. (%)
0.8
3.7±2.8
9.0±11.4
21.6±29.9
9.5±7.2
21.7 ±26.2
30.5 ±26.4
15.8±17.4
38.0±38.4
16.3 ±22.9
1 (100.0)
2 (66.7)
16 (69.6)
3 (37.5)
10 (58.8)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
32 (41.6)
0 (0.0)
1 (33.3)
6 (26.1)
5 (62.5)
7 (41.2)
6 (66.7)
2 (100.0)
3 (1OO.0)
11 (1OO.0)
41 (53.2)
0 (0.0)
1 (33.3)
4 (17.4)
3 (37.5)
2(11.8)
7 (77.8)
1 (50.0)
3 (100.0)
9 (81.8)
30 (39.0)
0 (0.0)
0 (0.0)
2 (8.7)
1 (12.5)
0 (0.0)
2 (22.2)
0 (0.0)
1 (33.3)
4 (36.4)
10 (13.0)
0 (0.0)
2 (66.7)
5 (21.7)
3 (37.5)
3 (17.6)
3 (33.3)
1 (50.0)
2 (66.7)
8 (72.7)
27 (35.1)
ECE, extracapsular extension; SVI, seminal Vesicle invasion; Nodal inv., nodal involvement.
Table II.
Correlation of Preoperative Gleason Sum with Final Pathological Findings
Final pathological findings
Preoperative
Gleason sum
2-4
5,6
7
8-10
Total
No. Pts.
No. (<%)
20
22
19
16
77
(26.0)
(28.6)
(24.7)
(20.8)
(100.0)
Organ
confined
No. («7o)
ECE
No. (<%)
SVI
No. (%)
Nodal inv.
No. (%)
14 (70.0)
9 (40.9)
4(21.1)
5 (31.3)
32(41.6)
4
12
14
11
41
4 (20.0)
6 (27.3)
12 (63.2)
8 (50.0)
30 (39.0)
1 (5.0)
1 (4.5)
5 (26.3)
3 (18.8)
10 (13.0)
(20.0)
(54.5)
(73.7)
(68.8)
(53.2)
Positive
margin
No. (<Po)
3
8
6
10
27
(15.0)
(36.4)
(31.6)
(62.5)
(35.1)
ECE, extracapsular extension; SVI,"seminal vesicle invasion; Nodal inv., nodal involvement.
poorly differentiated tumors with Gleason sums 7
and 8-10, respectively. Of the 77 patients, 32
(41.6%) had organ-confined disease pathologically.
Extracapsular extension was apparent in 41(53.2%),
seminal vesicle involvement in 30 (39.0%), nodal involvement in 10 (13.0%) and positive surgical margin in 27 (35.1%) patients.
Table I shows the distribution of staging of the
77 patients, based on rectal examination and correlation with the final pathological stage. Among
stage Tl patients, 70.4% had organ-confined cancer
and all clinical stage T3 cases had disease beyond
the capsule according to the final pathologic analysis. Over half of stage T2a-b cases had organconfined disease which was absent from stage T2c
patients. Of the 61 clinically localized tumors
(^T2), 32 (52.5%) were organ-confined at the final pathology. The incidence of extracapsular extension for stage Tl, T2 and T3 diseases was 25.9%,
52.9% and 100.0%, respectively. The corresponding
values for seminal vesicle and nodal involvement
were 18.5%, 35.3%, 81.3% and 7.4%, 8.8%,
31.3%, respectively.
440
Table II shows the distribution of patients by
preoperative Gleason sum and corresponding correlations with the final pathological stage. Graded increase was noted in extraprostatic extension with an
increase in the Gleason sum. The incidence of
organ-confined disease in patients with Gleason
sums 2-4, 5 or 6, 7 and 8-10 tumors was 70.0%,
40.9%, 21.1% and 31.3%, respectively. The corresponding values for extracapsular extension and
seminal vesicle involvement were 20.0%, 54.5%,
73.7%, 68.8% and 20.0%, 27.3%, 63.2%, 50.0%,
respectively. Those for nodal involvement and positive surgical margin were 5.0%, 4.5%, 26.3%,
18.8% and 15.0%, 36.4%, 31.6%, 62.5%, respectively. Of the 10 tumors with nodal involvement,
eight showed poorly differentiated histology of
Gleason sum 7 and above. Of the men with Gleason sum 7-10, 71.4% had extraprostatic disease and
22.9% positive pelvic lymph nodes.
Table III indicates the distribution of PSA levels
and correlations with the final pathological stage.
Of the 77 patients, 19 (24.7%) had preoperative serum PSA of 4.0 ng/ml or less and 73.7% organJpn J Clin Oncol 26(6) 1996
PREDICTION OF PATHOLOGICAL STAGE
Table III. Correlation of Preoperative PSA with Final Pathological Findings
Final pathological findings
PSA
(ng/ml)
0.0-2.0
2.1-4.0
4.1-10.0
10.1-15.0
15.1-20.0
20.1Total
No. Pts.
No. (%)
4 (5.2)
15 (19.5)
27 (35.0)
10 (13.0)
6 (7.8)
15 (19.5)
77 (100.0)
Organ
confined
No. (<%)
ECE
SVI
No. (%)
2 (50.0)
12 (80.0)
10 (37.0)
5 (50.0)
3 (50.0)
0 (0.0)
32 (41.6)
1 (25.0)
2 (13.3)
16 (59.3)
5 (50.0)
3 (50.0)
14 (93.3)
41 (53.2)
No. (%)
1 (25.0)
1 (6.7)
10 (37.0)
2 (20.0)
2 (33.3)
14 (93.3)
30 (39.0)
Nodal inv.
No. (%)
0 (0.0)
0 (0.0)
2 (7.4)
0 (0.0)
1 (16.7)
7 (46.7)
10 (13.0)
Positive
margin
No. (<7b)
1 (25.0)
3 (20.0)
4 (14.8)
6 (60.0)
3 (50.0)
10 (66.7)
27 (35.1)
ECE, extracapsular extension; SVI, seminal vesicle invasion; Nodal inv., nodal involvement.
Table IV. Correlation of Preoperative PSA, Gleason Sum and Clinical Stage with Final Pathological Findings
Final pathological findings
PSA
(ng/ml)
0.0-2.0
Preoperative
Gleason sum
2-6
Clinical
stage
Tl, T2
T3
2.1-4.0
2-6
7-10
4.1-10.0
2-6
7-10
Tl,
Tl,
Tl,
Tl,
T2
T2
T2
T2
T3
10.1-15.0
2-6
Tl, T2
7-10
Tl, T2
T3
T3
15.1-20.0
20.1-
2-6
Tl, T2
7-10
T3
2-6
Tl, T2
T3
7-10
Tl, T2
T3
No.
Pts.
3
1
11
4
11
13
3
5
1
3
1
5
1
4
1
2
8
Organ
confined
No. (%)
2 (66.7)
0 (0.0)
9 (81.8)
3 (75.0)
5 (45.5)
5 (38.5)
0 (0.0)
4 (80.0)
0 (0.0)
1 (33.3)
0 (0.0)
3 (60.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
ECE
SVI
No. (%)
0 (0.0)
1 (100.0)
2 (18.2)
0 (0.0)
5 (45.5)
8 (61.5)
3 (100.0)
1 (20.0)
1 (100.0)
2 (66.7)
1 (100.0)
2 (40.0)
1 (100.0)
3 (75.0)
1 (100.0)
2 (100.0)
8 (100.0)
No. (%)
1 (33.3)
0 (0.0)
1 (9.1)
0 (0.0)
1 (9.1)
6 (46.2)
3 (100.0)
1 (20.0)
0 (0.0)
1 (33.3)
0 (0.0)
1 (20.0)
1 (100.0)
4 (100.0)
1 (100.0)
1 (50.0)
8 (100.0)
Positive
Nodal inv.
margin
No. (%)
No. (%)
0 (0.0)
1 (33.3)
0 (0.0)
0 (0.0)
0 (0.0)
2 (18.2)
0 (0.0)
1 (25.0)
0 (0.0)
1 (9.1)
2 (15.4)
1 (7.7)
0 (0.0)
2 (66.7)
0 (0.0)
2 (40.0)
0 (0.0)
- 1 (100.0)
0 (0.0)
2 (66.7)
0 (0.0)
1 (100.0)
0 (0.0)
2 (40.0)
1 (100.0)
1 (100.0)
2 (50.0)
2 (50.0)
0 (0.0)
0 (0.0)
1 (50.0)
2 (100.0)
4 (50.0)
6 (75.0)
ECE, extracapsular extension; SVI, seminal vesicle invasion; Nodal inv., nodal involvement.
confined disease. Organ-confined disease was found
in 37.0% and 41.9% of patients at intermediate
PSA of 4.1 to 10.0 ng/ml and 4.1 to 20.0 ng/ml,
respectively. The incidence of extracapsular extension for tumors with PSA 0.0-4.0 ng/ml, 4.1-20.0
ng/ml and 20.1ng/ml or greater was 15.8%, 55.8%
and 93.3%, respectively. The corresponding values
for seminal vesicle and nodal involvements were
10.5%, 32.6%, 93.3% and 0.0%, 7.0%, 46.7%,
respectively. Seven of the 10 patients with pelvic
lymph node metastasis had PSA of 20 ng/ml or
greater.
Table IV shows the probability of pathological
stages as determined from a combination of
preoperative parameters. More locally advanced
tumors with less differentiated histology and higher
PSA had less chance of organ confinement. None
of the 15 patients (T1-T2, 6 and T3, 9) with PSA
exceeding 20 ng/ml had organ-confined tumors
pathologically. Ten of these patients had poorly
differentiated tumors with a Gleason sum of 7 or
more. Logistic regression analysis and log-likelihood
ratio chi-squared test indicated all levels of final
pathological stages to be predictable with greater
accuracy using a combination of the three variables.
All such predictions were better than those based
on a single variable. Table V summarizes the multivariate combinations of preoperative variables for
predicting final pathological stages.
441
EGAWA ET AL.
Table V.
Univariate and Multivariate Predictors of Final Pathological Stage by Logistic Regression Analysis with Log Likelihood Ratio Chi-squared Test
Pathological stage
ECE
SVI
Positive margin
Nodal inv.
Chi-squared
P value
Chi-squared
P value
Chi-squared
P value
Chi-squared
P value
Chi-squared
P value
11.3
0.01
10.2
0.017
11.1
0.011
7.2
0.065
2.9
0.40
Clinical stage and
PSA
36.9
0.00005
30.9
0.00005
27.6
0.0943
23.0
0.0003
11.5
0.0745
PSA and biopsy
grade
41.2
0.00005
34.1
0.00005
13.8
0.0002
20.9
0.0019
17.7
0.0071
Clinical stage
and biopsy grade
36.8
0.00005
26.5
0.0001
11.9
0.0006
24.5
0.0002
18.4
0.0054
Clinical stage, PSA,
and biopsy grade
30.5
0.00005
21.9
0.0013
11.3
0.0008
19.3
0.0017
5.8
0.4470
Clinical stage —•
Serum PSA
Biopsy grade —1
ECE, extracapsular extension; SVI, seminal vesicle invasion; Nodal inv., nodal involvement.
Table VI.
Comparison of Patients with Pathologically Organ-confined Disease According to Preoperative PSA
Present study
Partin
Catalona
et al.U)
No. (<%)
PSA
(ng/ml)
All pts.
No. (%)
P t s . ^ T 2 disease
No. (%)
Narayan
et a/.61
No. (%)
No. (%)
0.0-4.0
14/19 (73.7)
14/18 (77.8)
114/137 (83.2)
211/284(74.3)
7/10 (70.0)
4.1-10.0
10/27 (37.0)
10/24 (41.7)
193/287 (67.2)
131/246 (53.3)
193/263 (73.4)
10.1-15.0
5/10 (50.0)
5/8 (62.5)
77/127 (60.6)
15.1-20.0
3/6 (50.0)
3/5 (60.0)
31/66 (47.0)
20.1-
0/15 (0.0)
0/6 (0.0)
58/196 (30.0)
9/55 (16.4)
Total
32/77 (41.6)
32/61 (52.5)
473/813 (58.2)
382/703 (54.3)
et alJ1
31/118 (26.3)
61/133 (45.9)
J
I
Discussion
The ultimate goal of clinical staging is to narrow
differences between clinical and pathological staging. However, currently available modes for staging
of prostate cancer are rather inaccurate.'17i 16>
Moreover, the recent increase in the detection of
nonpalpable, nonvisible stage Tic disease has made
preoperative staging more challenging.9' '0| 17) The
combined use of PSA, clinical stage and biopsy
Gleason sum is advocated in North America to improve the preoperative predictability of the final
pathological stage.6"8' Though each variable correlates well with advancing clinical and/or pathological stage, a combination of these more accurately
predicted pathological stage than any single variable on an individual basis. Probability plots and
442
261/406 (64.3)
nomograms have been constructed to predict the final pathological staging.6"8'
The same model may not necessarily be applicable to Japanese patients since they may have a significantly lower serum PSA than Caucasians.9-18)
We used IMx PSA assay rather than the Hybritech
Tandem-R assay as in other studies.6"8' Differences
in these two assays have been shown to depend
primarily on the sample with its own particular
concentration of free PSA only at extremes of freeto-total PSA ratios. 19 '^ The results of the assays
are thus closely correlated and may be considered
virtually identical. Serum levels of testosterone have
been shown to be essentially the same among ethnic groups.2" The lower mean PSA in Japanese
males may be due primarily to the smaller average
gland volume as well as reduced 5a-reductase enJpn J Clin Oncol 26(6) 1996
PREDICTION OF PATHOLOGICAL STAGE
zymatic activity and less tissue concentration of dihydrotestosterone, since PSA gene expression and
glycoprotein production are under androgenic regulation.9' 18-21) Low serum PSA does not necessarily
indicate organ-confined disease6-22-M> and this may
apply particularly to the Japanese male population.
A given serum PSA for a Japanese male may have
a clinical meaning different from that for a Caucasian of the same age. Organ-confined disease was
found less frequently at the same PSA range in this
study, compared to North America, 52.2% versus
64.5-73.3% in patients with preoperative PSA of
10.0 ng/ml or lower.6-7-^ (Table VI) Clinically
localized tumors (^T2) in this PSA range also had
less probability of pathologically organ confined
disease (57.1%) in this study.
The above findings clearly demonstrate the importance of selecting an ideal cutoff value for PSAbased screening in Japanese males.9-2S) If the principal objective of prostate cancer screening is early detection of clinically significant, organ-confined
and potentially curable disease, a lower cutoff value
may perhaps be better, should specificity not to be
too greatly compromised.9-2i) The higher the PSA
value, the narrower the window of curability for
prostate cancer becomes. Tumor differentiation has
been shown to be inversely correlated with the serum PSA level.22' Inclusion of many poorly
differentiated tumors in our study may have affected these results. Lack of grade- and stage-specific
serum PSA data regarding pathological stage in the
literature precludes any definitive conclusions. This
hypothesis should be tested in a prospective study.
By logistic regression analysis and the loglikelihood ratio chi-squared test, preoperative PSA,
clinical stage and preoperative Gleason sum were
found to be significantly associated with the final
pathological stage. These variables used in combination make possible more accurate prediction than
that based on a single variable. The small number
of cases in this study obscures differences in combination of these 2 and 3 variables. A model for
accurately predicting the final pathological stage in
oriental male populations should be established using samples of larger size.
Pathological stages as determined by various
combinations of preoperative parameters are
presented in Table IV. For locally advanced tumors
with less differentiated histology and higher PSA,
organ confinement is less probable. In this study,
tumors with PSA of 4.1-10.0 ng/ml had 40-100%
chance of being pathologically advanced, depending
on the tumor grade and clinical stage. Clinically
localized cancers (^T2) with well to moderately
differentiated histology of this PSA had more than
a 50% chance of being locally advanced disease
pathologically. Probability increases as tumors ac-
quire a poorly differentiated histology. No patient
with PSA higher than 20 ng/ml had organ-confined
tumors, regardless of the tumor grade or stage.
One quarter of tumors with a PSA level of 0.0-4.0
ng/ml already had extraglandular spread. The levels of PSA alone could thus not reliably predict the
final pathological stage on an individual basis but
could do so at 20 ng/ml or greater. Of the 10
cases with pelvic lymph node metastasis, seven had
a PSA level of 20 ng/ml or greater and eight had
poorly differentiated tumors. Five of these had
stage T3 disease. Patients with a PSA level of 20
ng/ml or greater, a Gleason sum of 7 or more and
local clinical stage T3 thus have a greater likelihood
of nodal involvement. Pelvic lymph node dissection
may be omitted in well selected patients without
these adverse findings. More detailed subcategorization should be possible with a greater number of
cases.
Our experience is limited owing to the small
number of patients, use of archival serum samples
and interconversion of PSA data in this study.
Measurable PSA is known to be lost with
prolonged freezing even at -80°C. 26) The mean
coefficient of variation (±SD) for serum PSA in
fresh and stored pairs is 9.2% (±16.6%) after 3-5
years of storage. Though the period of storage was
much shorter in this study, PSA degradation may
possibly have affected the present data to some extent. For five patients, PSA data could^be obtained
only from Eiken polyclonal radioimmunoassay. The
validity of inter-conversion of PSA may be compromised by the possibility of inter-institutional as
well as inter-assay variation. The conclusions of this
study should thus be considered preliminary, since
no means were available to control these possibilities. Further investigation is warranted.
Acknowledgments
This work was supported in part by a Grant from the
Ministry of Health and Welfare of Japan (7-42).
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