In this retrospective cohort study, data were extracted from the Danish Ocular Oncology Group Database containing complete data on all patients diagnosed with
retinoblastoma , and obtained from the Danish
Cancer Registry, which includes information on all patients with
cancer from 1943 to December 31, 2013. Data analysis was conducted from December 1, 2017, to October 1, 2019. Data on 323 patients were included.
Exposures: Standardized incidence rate, excess absolute risk, cumulative incidence of SPC, and mortality from SPC. Association of heritability and treatment with outcomes was estimated.
Results: Of the 323 patients included in the analysis, 181 were men (56%), 133 had heritable
retinoblastoma (41%), and 190 had nonheritable
retinoblastoma (59%). The median age at diagnosis of SPC was 32.4 (interquartile range, 15.4-43.9) years in patients with heritable
retinoblastoma and 38.6 (interquartile range, 20.5-49.4) years in those with nonheritable
retinoblastoma. Twenty-five SPCs were identified in patients with heritable
retinoblastoma vs 14 in patients with nonheritable
retinoblastoma. Standardized incidence rate (SIR) of SPC in patients with heritable
retinoblastoma was 11.39 (95% CI, 7.37-16.81) with an excess absolute risk of 70 cases per 10 000 person-years; the highest SIRs were for
sarcoma (181.13; 95% CI, 98.94-303.92) and
malignant melanoma (26.78; 95% CI, 9.78-58.30). The SIR for SPC in patients with nonheritable
retinoblastoma was 1.52 (95% CI, 0.81-2.60). The cumulative incidence of SPCs at age 60 years was significantly higher in patients with heritable
retinoblastoma (51%) compared with those with nonheritable
retinoblastoma (13%) (P < .001) (hazard ratio, 5.0; 95% CI, 2.5-10.3). No significant differences were identified in overall risk of SPC in patients with heritable
retinoblastoma treated with 3 different modalities: external
radiotherapy, plaque (but no external)
radiotherapy, and enucleation only, but an increased proportion of
sarcomas was noted in the irradiated field. Mortality due to SPC was also higher in survivors of heritable
retinoblastoma compared with those with nonheritable
retinoblastoma (cumulative mortality, 34% vs 12% at age 60 years; P = .03).
Conclusions and Relevance: The findings of this study suggest that the incidence and mortality associated with SPC were significantly higher in patients with heritable
retinoblastoma vs patients with nonheritable
retinoblastoma. The largest increases in risk were noted for
sarcoma and
malignant melanoma. External
radiotherapy did not appear to increase the risk. These findings are relevant when treating patients with
retinoblastoma to manage the risk for SPC.