Survival impact of second primary cutaneous and non‐cutaneous melanoma in melanoma survivors

Background Melanoma survivors have a high risk of developing second primary neoplasms, both cutaneous melanoma (SPCM) and non‐cutaneous melanoma (SPNCM), but little is known about the survival impact of the diagnosis of SPCM and SPNCM. Objective To compare overall survival between melanoma survivors with first primary melanoma and SPCM/SPNCM by stage at diagnosis of second primary neoplasms. Methods Among cutaneous (CM) and non‐cutaneous melanoma (NCM) survivors of all ages, SPCM ( N = 7314) or SPNCM ( N = 157) between 2004 and 2020 were identified from the Surveillance, Epidemiology, and End Results 17 Research Plus database. Flexible parametric modelling was conducted to evaluate the time‐varying effect of SPCM and SPNCM, compared to single melanoma, on survival. Results Over the study period, 3.4% of patients had a SPCM (12.9% regional/distant‐stage) and 0.1% had a SPNCM (36.3% regional/distant or unknown‐stage). Compared with single CM, patients with SPCM (regional/distant‐stage hazard ratio [HR] = 1.71, 95% confidence interval [CI] = 1.55–1.89; localized‐stage HR = 1.09, CI = 1.01–1.18) and regional/distant‐stage SPNCM (Year 1: HR = 1.56, CI = 0.81–3.03) had worse overall survival. Among NCM survivors, regional/distant‐stage SPCM (HR = 2.67, CI = 1.73–4.13) had a more pronounced impact on decreased overall survival than localized‐stage SPCM (HR = 1.19, CI = 0.71–1.99) when compared with single NCM, with similar trends seen for regional/distant‐stage SPNCM (Year 2: HR = 1.39, CI = 0.76–2.54) relative to localized‐stage SPNCM (Year 2: HR = 0.96, CI = 0.61–1.50). Conclusions The reduction in survival among melanoma survivors with SPCM and SPNCM suggests the potential need for prevention and early detection of SPCM and SPNCM.