Incidence and survival of secondary malignancies after external beam radiotherapy for prostate cancer in the Surveillance, Epidemiology, and End Results database

Introduction: The study objective was to investigate the incidence of secondary bladder (BCa) and rectal cancers (RCa) after external beam radiotherapy (EBRT) for prostate cancer (PCa) compared to radical prostatectomy (RP) alone, and to compare cancer-specific survival of these secondary neoplasms to their primary counterparts. Methods: This retrospective cohort study included men in the Surveillance, Epidemiology, and End Results cancer registry with a diagnosis of non-metastatic, clinically node-negative PCa treated with either RP or EBRT from 1995–2011 and allowed a minimum five-year lag period for the development of secondary BCa or RCa. Patients were divided into two eras, 1995–2002 and 2003–2011, to examine differences in incidence of secondary malignancies over time. Univariable and multivariable competing risk analyses with Fine-Gray subdistribution hazard and cause-specific hazard models were used to examine the risk of developing a secondary BCa or RCa. Competing risks analyses were used to compare cancer-specific survival of primary vs. secondary BCa and RCa. Results: A total of 198 184 men underwent RP and 190 536 underwent EBRT for PCa. The cumulative incidence of secondary BCa at 10 years was 1.71% for RP, and 3.7% for EBRT (p<0.001), while that of RCa was 0.52% for RP and 0.99% for EBRT (p<0.001). EBRT was associated with approximately twice the risk of developing a secondary BCa and RCa compared to RP. The hazard of secondary BCa following EBRT delivered during 2003–2011 was 20% less than from 1995–2002 (p<0.09, Fine-Gray model), while that of secondary RCa was 31% less (p<0.001) (hazard ratio 0.78, p<0.001) for Fine-Gray and cause-specific hazard models. In the Fine-Gray model, the risk of death from BCa was 27% lower for secondary BCa after RP compared to primary BCa, while the risk of death was 9% lower for secondary BCa after EBRT compared to primary BCa. There was no difference in RCa-specific survival between primary or secondary RCa after RP or EBRT. Conclusions: The risk of BCa and RCa is approximately twice as high for men undergoing EBRT for localized PCa compared to RP, but that risk is declining, likely reflecting advancements in radiation delivery. The development of secondary RCa or BCa does not confer an elevated risk of death compared to their primary counterparts.