Impact of initial stage on metastatic melanoma survival

Patients diagnosed with metastatic melanoma have varied clinical courses, even in patients with similar disease characteristics. We examine the impact of initial stage of melanoma diagnosis, BRAF status of primary melanoma, and receiving adjuvant therapy on postmetastatic overall survival (pmOS). We studied melanoma patients presenting to Perlmutter Cancer Center at New York University and prospectively enrolled in New York University melanoma biospecimen database and followed up on protocol-driven schedule. Patients were stratified by stage at initial melanoma diagnosis as per AJCC 7th ed. guidelines. pmOS was determined using the Kaplan-Meier method and Cox's proportional hazards models were used to assess hazard ratios (HRs). Three hundred and four out of 3204 patients developed metastatic disease over the time of follow-up (median follow-up 2.2 years, range: 0.08-35.2 years). Patients diagnosed with stage I (n=96) melanoma had longer pmOS (29.5 months) than those diagnosed with stage II (n=99, pmOS 14.9 months) or stage III (n=109, pmOS 15.1 months) melanoma (P=0.036). Initial stage of diagnosis remained significant in multivariate analysis when controlling for lactate dehydrogenase and site of metastases [primary diagnosis stage II (HR 1.44, P=0.046), stage III (HR 1.5, P=0.019)]. Adjuvant treatment was associated with better survival but BRAF mutation status did not show an association. Our data challenge the general assumption that primary melanomas converge upon diagnosis of metastatic disease and behave uniformly. Primary stage of melanoma at the time of diagnosis may be prognostic of outcome, similar to lactate dehydrogenase and metastatic disease sites.