Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors

Background Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs. Methods Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914–2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death. Results Hereditary survivors had statistically significantly increased SMN risk ( N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4–13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1–17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0–37.2) for a first SMN and 6.0% (95% CI 3.8–8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma ( N = 25; SIR = 0.8; 95% CI 0.5–1.2). Conclusion Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.