Subsequent risk of non-keratinocyte skin cancers in adult cancer survivors: a SEER-based cohort study

Objective To characterise the risk of subsequent primary non-keratinocyte skin cancers (NKSCs) among adult-onset cancer survivors. Design Data analysis of this population-based cohort study was conducted from September to November 2024. Setting The data are based on 17 Surveillance, Epidemiology and End Results (SEER) registries from 2000 to 2021. Participants Survivors of first primary cancers diagnosed in individuals aged 20–84 years between 2000 and 2021, across 17 registries in the SEER Program Primary and secondary outcome and measure Primary outcomes were a statistically significant increase in the incidence of subsequent NKSCs. Standardised incidence rate (SIR) and excess risk analysis were used to evaluate the risk of subsequent NKSCs after different primary cancers. Results Among 5 691 336 survivors (51.3% male), 31 529 subsequent NKSCs were observed during a total follow-up of 36 440 569 person-years (mean, 6.4 years). The risk of subsequent NKSCs was increased after the first primary cancer (SIR, 1.12 (95% CI 1.10 to 1.13)). Across 35 first primary cancers, 19 showed a statistically significant rise in subsequent NKSC incidence. The highest SIR for subsequent NKSCs was observed after eye and orbit cancer (SIR, 2.96 (95% CI 2.55 to 3.41)), followed by cutaneous melanoma (SIR, 2.67 (95% CI 2.41 to 2.94)) and chronic lymphocytic leukaemia (SIR, 2.24 (95% CI 2.10 to 2.38)). Across NKSC types, cancer survivors were more likely to develop subsequent hemangiosarcoma (SIR, 2.66 (95% CI 2.31 to 3.05)), adenocarcinoma, not otherwise specified (SIR, 2.14 (95% CI 1.53 to 2.91)) and sebaceous adenocarcinoma (SIR, 1.70 (95% CI 1.57 to 1.83)). 10 specific first primary cancers demonstrated a consistently high risk of several specific NKSCs throughout the study period. Furthermore, the risk of subsequent NKSCs among cancer survivors was largely elevated following radiotherapy or chemotherapy (range, 13%–18%), especially for hemangiosarcoma. Conclusions and relevance Several types of primary cancers were strongly linked to an increased risk of subsequent NKSCs, underscoring the critical importance of implementing continuous surveillance and proactive prevention strategies to mitigate the risk of developing subsequent primary NKSCs among cancer survivors.