Patterns of cause of death among patients with subsequent primary malignancies after cutaneous melanoma: A SEER-based analysis (2000–2022).

e21605 Background: As survival after cutaneous melanoma improves, subsequent primary malignancies (SPMs) and non-cancer comorbidities increasingly influence long-term outcomes. We evaluated causes of death (COD) and clinicodemographic characteristics among decedents with melanoma and multiple primaries. Methods: We conducted a retrospective, population-based analysis using Surveillance, Epidemiology, and End Results (SEER) data from 2000–2022. The cohort included decedents with cutaneous melanoma and two or more primary malignancies in whom melanoma preceded a subsequent primary cancer (N = 29,942). Cause of death was obtained from SEER cause-specific classifications and examined in relation to clinicodemographic and treatment characteristics. Variables included sex, age at diagnosis, race/ethnicity, primary site (ICD-O-3/WHO 2008), SEER Summary Stage 2004, and treatment indicators (chemotherapy, radiation, surgery, regional lymph node surgery). Descriptive statistics and frequency distributions were generated, with graphical displays used to visualize cause-of-death patterns and temporal trends. Results: The cohort was predominantly male (71.6%) and non-Hispanic White (96.4%); mean age at diagnosis was 74.4 years (median 76; range 16–90). By sequence number, most patients had ≥2 primaries (2nd primary: 73.3%; 3rd: 17.8%; 4th: 4.9%). The most common indexed primary site category was melanoma of the skin (40.2%), followed by lung and bronchus (9.9%) and prostate (7.2%). Summary stage at diagnosis was localized in 33.9%, distant in 22.0%, in situ in 16.6%, and unknown/unstaged in 8.1%. Chemotherapy was recorded in 17.8%, while radiation was uncommon overall (none/unknown 84.2%; beam 13.1%). COD was most frequently melanoma (17.0%), followed by diseases of heart (13.1%), lung and bronchus cancer (9.7%), and “other cause of death” (9.1%). Additional notable COD categories included pancreas (3.6%), cerebrovascular disease (3.0%), and non-Hodgkin lymphoma (2.0%). Conclusions: In patients with melanoma and multiple primaries, melanoma remains a leading COD, but cardiovascular mortality represents a substantial competing risk. These findings support integrated survivorship strategies emphasizing both second-cancer surveillance and aggressive cardiovascular risk assessment and management.