Second primary cancer risk after penile squamous cell carcinoma: A population-based study.

PURPOSE: Survivors of penile squamous cell carcinoma (SCC) may be at increased risk of second primary cancers (SPCs), but population-based data in the United States are limited. We evaluated SPC risk among pSCC survivors using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We conducted a population-based retrospective cohort study using SEER (2000-2022). Standardized incidence ratios (SIRs) and excess absolute risks (EARs) were used to compare SPC risk with the general population. Fine-Gray competing-risk regression was performed to identify factors associated with SPC development. RESULTS: Among 5,378 patients with penile SCC, 599 (11.1%) developed at least 1 SPC. Overall SPC risk was significantly elevated compared with the general population (SIR 1.17; 95% CI 1.09-1.27). Higher relative risks were observed among patients younger than 60 years (SIR 1.48), Black individuals (SIR 1.58), and those with basaloid SCC (SIR 2.12). SPC risk was greatest within the first year after diagnosis (SIR 1.78) and remained elevated within the first 5 years. The highest site-specific risk was observed for cancers of the anus, anal canal, and anorectum (SIR 5.00). In competing-risk analyses, Black race, and basaloid histology were independently associated with increased SPC risk, while advanced stage and absence of surgery were associated with lower observed incidence, likely reflecting competing mortality. CONCLUSIONS: Survivors of penile SCC have a significantly increased risk of SPCs, particularly HPV-related malignancies. These findings provide important insight into the timing and distribution of SPC risk following penile SCC and may help inform future survivorship research and clinical awareness of SPC risk in this population.