A total of 89 515 patients survived 2 months or longer following a diagnosis of a primary melanoma. The patients were followed up for a maximum of 34 years (median, 9.2 years); 53.4% of the patients were men and 46.6% were women (). The median age at first melanoma diagnosis was 54 years, with men having a higher median age at diagnosis than women (56 vs 52 years, respectively). The proportion diagnosed at ages 50 years and older was also substantially greater among men than women (63.9% vs 50.3%, respectively). Among men, the most common site of the first melanoma was the trunk (41.5%), whereas in women, it was the lower limbs (32.7%). In men (37.1%) and women (42.6%), the most frequent histological diagnosis of the first primary melanoma was superficial spreading melanoma. The large majority of patients were surgically treated (94.3%), and few patients received radiation treatment (2.1%).
Characteristics of Patients With Cutaneous Malignant Melanoma in the 9 SEER Registries From 1973–2006a
Of the 89 515 patients diagnosed with an initial melanoma, 12.1% developed 1 or more subsequent primary tumors (), including 9348 patients (10.4%) with 2 primary cancers, 1290 (1.4%) with 3 primary cancers, and 219 (0.2%) with 4 or more primary cancers. A total of 96.4% of patients had their first and all subsequent cancers confirmed via histological analysis.
In survivors of a first primary melanoma, the overall risk of developing a subsequent primary cancer increased by 28% among men and women who survived for 2 months or longer (O:E, 1.28; O, 12 559 [95% CI, 1.26–1.30]; EAR, 34/10 000 person-years) (). This excess was primarily owing to subsequent primary melanoma (O:E, 8.61), with 25% of the subsequent cancers being primary melanomas. The risk of subsequent primary melanoma was highest 2 months to 1 year after the initial melanoma diagnosis (O:E, 16.94), with the risk decreasing as the latency period increased. At 20 years or longer after the initial melanoma diagnosis, however, the risk was still elevated (O:E, 5.58 [95% CI, 4.80–6.44]). The relative risk of subsequent primary melanoma was similar for men and women (O:E, 8.40 [95% CI, 8.04–8.78]; EAR, 43/10 000 person-years; and 9.00 [8.479.54]; EAR, 24/10 000 person-years, respectively).
Risk of Selected Subsequent Primary Cancers After Melanoma in the 9 SEER Registries From 1973–2006a
There were, however, significantly elevated risks for specific subsequent primary cancers other than melanoma. For each of the cancer types listed in Table 2, increased risks among melanoma survivors were noted in comparison to what would be expected in the general population. The most common cancers with elevated risks after an initial melanoma were prostate cancer (O:E, 1.15; EAR, 3.49), female breast cancer (1.10; 1.34), and non-Hodgkin lymphoma (NHL) (1.25; 1.18) (). Risks were also significantly increased for cancers of the salivary gland, small intestine, kidney, ocular melanoma, and thyroid as well as soft tissue sarcomas and chronic lymphocytic leukemia.
We evaluated the risks for subsequent primary cancers among melanoma survivors in 3 age groups: younger than 30 years, 30 through 49 years, and 50 years and older. Patients younger than 30 had the greatest relative risk for developing subsequent cancers after a melanoma diagnosis (O:E, 2.41 [95% CI, 2.17–2.68]) (). This was owing to the markedly higher relative risks of developing subsequent melanoma in those initially diagnosed at ages younger than 30 (O:E, 13.40 [95% CI, 11.66–15.33]) ( and ). Among those aged 30 through 49 years, the relative risk of second primary melanoma was 8.74; among those aged 50 years and older, it was 8.23. , shows that the EAR for developing melanoma increased as patients aged. The EAR for developing subsequent melanomas was highest among those aged 50 years and older at the first melanoma diagnosis (43.89) ().
Figure Risk of subsequent primary cancers after cutaneous malignant melanoma (CMM) diagnosis by age groups in the 9 SEER (Surveillance, Epidemiology, and End Results) Registries, 1973–2006. A, Relative risk (observed to expected ratio [O:E]). B, Excess (more ...)
Risk of Subsequent Melanoma by Sex, Age, and Tumor Characteristics of Initial Melanoma Based on Data From the 9 SEER Registries, 1973–2006
Overall, individuals with their initial melanoma on the head or neck had the highest risk of developing subsequent primary melanomas (O:E, 9.69 [95% CI, 8.97–10.45]; EAR, 46.72) compared with those with initial melanomas on other anatomic sites (). Individuals with melanoma of the head and neck were also older (mean age at diagnosis, 61.6 years) compared with those diagnosed with melanoma at other sites (mean age range, 50.9–55.4 years). Women with initial head and neck melanoma had a higher relative risk (O:E, 13.22 [95% CI, 11.43–15.20]) of developing a subsequent melanoma than did men (8.72 [7.96–9.54]). Men who had their first melanoma on the head and neck, however, had higher EARs of developing subsequent melanomas than did women (51.59 and 38.32, respectively). The most frequent result of histological analysis of the melanomas of the head and neck in both sexes was lentigo maligna melanoma (data not shown).
The lack of central review of histological characteristics limited our ability to fully evaluate the risk of subsequent melanomas according to histological type, but there did not appear to be large differences. Based on limited data, risks of subsequent melanomas appeared lower for first acral lentiginous melanoma (data not shown). Risks by thickness were also difficult to interpret. Overall, patients whose first melanoma was more than 2.01 mm thick (based on fewer observations) had higher risks for developing subsequent melanomas (). This group, however, is the group that is most likely to have misclassification of second melanomas owing to misdiagnosis of local recurrence as a new primary melanoma.
compares thickness of multiple primary melanomas. Second melanomas were significantly more likely to be thin compared with the first of multiple primary melanomas (77.9% vs 70.3% diagnosed at <1.00 mm, respectively; P<.001). Also, women had a higher percentage of thin melanomas than did men. However, we could not discount a calendar effect for these trends. When we stratified the thickness of subsequent melanomas by calendar periods, there was a higher percentage of first, second, and third melanomas with a thickness at diagnosis of less than 1.00 mm during the period 1997–2006 in comparison to 1988–1996 (data not shown).
Thickness of Multiple Primary Melanomas by Sex in the 9 SEER Registries, 1988–2006a