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Although incidence of second primary malignancies (SPMs) has been investigated in patients with cutaneous melanoma and uveal melanoma, limited studies have investigated their occurrence subsequent to conjunctival melanoma (CM). We conducted a retrospective observational study to assess incidence of SPMs in patients with primary CM and to identify associated risk factors. Cases of first primary CM diagnosed from 2000 to 2018 were extracted from the national cancer database Surveillance, Epidemiology, and End Results Program. Standardized incidence ratios (SIR) and excess absolute risk (EAR) of SPMs were calculated compared to a matched cohort from the general population with similar sex, race, age group, and calendar year. EAR was per 10,000 individuals, and a  P -value of &lt;0.05 was considered significant. A total of 471 patients met inclusion criteria, 57 (12.1%) of whom developed second primary malignancies (excluding eye and orbit melanomas) over an average (±SD) follow-up period of 6.8 (±5.0) years. Average age at diagnosis for the overall cohort was 60.2 (±18.6) years. Patients with CM demonstrated a significantly increased risk for overall SPMs relative to the general population, even after excluding eye and orbit melanomas (SIR 1.52; 95% confidence interval [CI], 1.15–1.97; EAR 67.58). Specific sites and malignancy types with increased risk were cutaneous melanoma (SIR 7.95; 95% CI, 4.45–13.12; EAR 45.34), ophthalmic non-melanoma malignancies (SIR 80.92; 95% CI, 2.05–450.84; EAR 3.41), and non-intrahepatic biliary malignancies (SIR 11.72; 95% CI, 1.42–42.32; EAR 6.32). Risk of overall SPMs (excluding eye and orbit melanomas) was significantly increased 5–10 years from diagnosis date. Patients with CM had an increased incidence of SPMs compared to the general population. Specifically, these patients developed more cutaneous, ophthalmic non-melanoma, and non-intrahepatic biliary malignancies. These second neoplasms could be due to shared pathophysiology or mutual risk factors. Patients with CM may benefit from surveillance for SPMs, such as annual age-appropriate screenings in the first 10 years after diagnosis.

Second Primary Malignancies following a Diagnosis of Conjunctival Melanoma