Cutaneous Malignant Melanoma The science behind the guidelines For decades the frequency of cutaneous melanomas worldwide has been increasing faster than any other cancer. Melanomas cause about 90 percent of skin cancer mortality. Even seemingly small lesions can be life-threatening because just a few millimeters in depth of invasion can effectively make the difference between life and death. Melanomas are malignant tumors which derive from certain melanincontaining cells in the body and pre-dominantly manifest on the skin. In rare cases, melanomas may also appear in the eye (choroid, conjunctiva or uvea), in the meninges or on mucosal surfaces in different locations. In relation to their size, melanomas have a very high tendency to metastasize, which leads to an unfavorable prognosis. Melanomas therefore cause about 90 percent of skin cancer-associated mortality, although other skin cancers are considerably more common clinically. Despite this, melanomas are usually curable if recognized and treated at an early stage. Today, about 90 percent of melanomas are without obvious metastasis at the time of diagnosis. Epidemiology Sun exposure during childhood is an important risk factor for developing melanomas. The incidence of melanomas has steadily increased in the white population worldwide over the last few decades, especially in areas with high sun exposure. At an average of 6 percent per year, the increase of melanomas over the last 50 years has been faster than for any other cancer. In central Europe, the incidence averages about 10 to 12 cases per 100,000 inhabitants per year, in the United States 10 to 25 cases, and the highest incidence rates are reported from Australia, with 50 to 60 cases per 100,000. In ethnic groups with stronger pigmented skin, like native African and Asian populations, melanomas are very rare but no less serious. Graph 1: Melanoma incidence in the white U.S. population over 1970-201011 Melanoma incidence rate per 100,000 USA (white population) 30 25 20 15 10 Source: seer.cancer.gov/faststats/ 5 1970 1975 1980 1985 1990 1995 2000 2005 2010 Munich Re Cutaneous Malignant Melanoma. Page 2/4 Risk factors for developing melanomas It is generally accepted that sun exposure plays a major role in the develop ment of melanomas. Only 5–10 percent of melanomas are related to hereditary factors. Sun exposure during childhood seems to have more impact than during adulthood, which is in contrast to epithelial skin cancer. Number of moles and atypical moles are indicators for the risk of melanomas. The number of melanocytic nevi (moles) on the body surface can be seen as an indicator for the risk of developing melanoma, where the probability for melanomas steadily increases with the number of moles on the skin4. In the presence of atypical moles, the risk further increases. Atypical moles are moles with either clinical atypical findings (e.g., size over 5 mm or irregular borders) or microscopic abnormalities. To take this risk into consideration, the impairments “atypical mole syndrome” and dysplastic nevus syndrome have been included in EDGE. The atypical mole syndrome is defined according to the following criteria: ■■ 50 to 100 or more nevi and ■■ at least one ≥ 8 mm diameter and ■■ at least one with atypical features Depending on the number of atypical moles and a family history of melanomas, there is a wide range of melanoma risk and therefore extra-mortality in this impairment4, 5. Table 1: Odds ratios of melanoma in relation to the number of common and atypical nevi5 Numbers of atypical nevi Numbers of common nevi 0 1 ≥2 0–24 1.0* 5.9 5.5 25–49 1.8 6.5 2.0 50–99 2.4 5.6 12.0 ≥ 100 2.6 6.2 53.5 *Odds ratios Classification of melanoma in EDGE EDGE ratings for melanoma have been revised according to the latest international prognostic standards. In 2009, a new internationally acknowledged staging classification for melanomas was instituted by the American Joint Committee on Cancer (AJCC) after analysis of a large database of melanoma patients from 13 international cancer centers including Australia and Europe3. The investigations of the AJCC are the largest prognostic factor studies on melanoma patients worldwide. The staging system is based on melanoma thickness in mm and presence or absence of lesion ulceration as the two major prognostic indicators. Additionally, T1 tumors without ulceration are categorized into T1a or T1b according to mitotic rate. This was a change compared to the previous classification, where Clark’s level of invasion had been used instead of mitotic rate1. (Mitotic rate data may not always be reported, e.g., in older pathology reports, therefore, in EDGE, Clark’s level can still be used in absence of mitotic rate data for classifying T1 lesions). According to the AJCC staging analysis, the location of melanomas (e.g. trunk, extremities, head) and growth patterns (e.g. lentigo maligna, superficial spreading, nodular) need not be taken into account for determining the prognostic staging group1. Munich Re Cutaneous Malignant Melanoma Page 3/4 Table 2: Classification of T stages in AJCC 2009 melanoma staging3 Classification T Thickness (mm) Ulceration status/Mitoses Tis NA NA T1 ≤ 1.00 a: Without ulceration and mitosis < 1/mm2 b: With ulceration or mitoses ≥ 1/mm2 T2 1.01–2.00 a: Without ulceration b: With ulceration T3 2.01–4.00 a: Without ulceration b: With ulceration T4 > 4.00 a: Without ulceration b: With ulceration Graph 2: Survival of melanoma patients related to staging published by AJCC 20093 Survival rate proportion 1.0 0.9 0.8 0.7 0.6 T1a (n = 9,452) T2a (n = 6,529) T3a (n = 3,127) T4a (n = 1,064) T1b (n = 2,389) T2b (n = 1,517) T3b (n = 2,164) T4b (n = 1,397) Source: Final version of 2009 AJCC melanoma staging and classification3 0.5 0.4 0.3 0.2 0.1 0 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 Time (years) Graph 3: Melanoma ten-year mortality rate in relation to tumor thickness2 10-year mortality rate ( percent) 100 80 60 40 Source: Prognostic factor analysis of 17,600 melanoma patients: validation of the American joint committee on cancer melanoma staging system2 20 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Tumor thick ness (mm) Looking at the prognosis of melanomas, it is worth noting that a very small increase of thickness in melanomas makes a big difference in terms of survival. Most of the prognostic impact takes place within the first four millimeters where the ten-year mortality rate increases from 5 percent to 50 percent (see Graph 3). The new AJCC staging system has been implemented into the melanoma section in EDGE. The Clark’s level can still be used instead of mitotic rate, because there may be no information about mitosis in cases dating back some years or depending on the reporting lab. Munich Re did an extensive extramortality analysis on the SEER (Surveillance Epidemiology and End Result) database of the U.S. National Cancer Institute using the AJCC staging system as the prognostic grid10. Munich Re Cutaneous Malignant Melanoma Page 4/4 The most frequent T1a melanomas have virtually normal survival rates, but then prognosis dramatically deteriorates with minimal increase of the tumor depth. On the basis of our analysis, the most frequent melanoma, stage 1A (T1aN0M0), shows virtually normal survival rates and can be accepted as standard for life. Progressively higher stages demonstrate increasing mortality with stage IIB being insurable only at highly substandard rates. Fortunately, the vast majority of newly diagnosed melanomas today fall into insurable categories and again most of them into the favorable T1a group. Our results from the SEER database are on all stages congruent with the published survival rates from the AJCC studies1, 3. One result for Stage IB (T1bN0M0) as an example is given in Graph 4. Graph 4: Survival with derived excess mortality (patients vs. normal population) Survival ( percent) Excess death rate (per mille) 100 16 14 80 12 10 60 8 Melanoma Stage IB (T1bN0M0), N = 4526 Patients Normal population 40 6 4 20 Source: Munich Re own calculations based on U.S. SEER data base10 2 0 0 1 EDGE allows rapid and reliable risk assessment on the basis of only a few prognostic criteria. 5 10 15 Years after diagnosis 1 5 10 15 Years after diagnosis It is also evident from our results – as well as consistently shown by other studies – that melanomas bear a significant long-term risk going beyond ten years after diagnosis7, 8, 9. In a study at Duke University among 651 long-term melanoma survivors, 25 percent developed recurrent disease after more than ten years7. Also ultra-late recurrences after more than 15 years are not uncommon9. Summary Melanoma ratings are now based on the most recent AJCC staging system. Extramortalities have been calculated based on the U.S. SEER database and have been compared internationally. Results show that prognosis of melanoma rapidly deteriorates with increasing tumor stage. Fortunately, these early diagnosed melanomas constitute the majority of all patients. In many cases, melanomas bear a long-term risk which definitely goes beyond ten years after diagnosis. Literature Balch CM et al. Final version of the American joint committee on cancer staging system for cutaneous melanoma. Journal of clinical oncology 2001; 19: 3635–3648 2 Balch CM et al. Prognostic factor analysis of 17,600 melanoma patients: validation of the American joint committee on cancer melanoma staging system. Journal of C linical Oncology 2001; 19: 3622–3634 3 Balch CM et al. Final version of 2009 AJCC melanoma staging and classification. Journal of Clinical Oncology 2009; 27: 1–8 4 Bauer J, Garbe C. Acquired melanocytic nevi as risk factor for melanoma development. A compre hensive review of epidemiological data. Pigment Cell Res 2003; 16: 297–306 5 Bataille et al. Risk of cutaneous melanoma in relation to the number, types and sites of naevi: a 1 Dr. Jürgen Becher is a Senior Medical Consultant for Munich Re at the Centre of Competence for Medical Risks Research, Underwriting & Claims. For more information, contact Dr. Mark Skillan, Vice President and Medical Director at Munich American Reassurance Company. He can be reached at [email protected]. NOT IF, BUT HOW case-control study. British Journal of Cancer 1996; 73: 1605–1611 Berrino et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study. Lancet Oncology 2007; 8: 773–783 7 Crowley NJ, Seigler HF. Late recurrence of malig nant melanoma. Annals of Surgery 1990; 212: 173– 177 8 Gamel JW et al. The long term clinical course of patients with cutaneous melanoma. Cancer 2002; 95: 1286–1293 9 Tsao H, Cosimi AB, Sober AJ. Ultra-late recurrence (15 years or longer) of cutaneous melanoma. Cancer 1997; 79: 2361–2370 10 seer.cancer.gov/data/ 11 seer.cancer.gov/faststats/ 6 © 2013 Munich American Reassurance Company, Atlanta, Georgia
© Copyright 2024 Paperzz