Impact of prostate cancer radiotherapy on the biological behavior and specific mortality of subsequent bladder cancer

Background The impact of different radiotherapy modalities on the development and characteristics of second primary bladder cancers (BCa) and BCa-specific mortality (BCa-SM) remains unclear. Thus, we evaluated the incidence and biological behavior of subsequent BCa and related survival in patients who underwent radiation therapy for prostate cancer (PCa). Methods A total of 530,581 patients in the surveillance, epidemiology, and end results database with localized PCa between 1988 and 2013 were identified. PCa treatments included radical prostatectomy (RP), external beam radiotherapy (EBRT), radioactive implants (RI), and combined EBRT and RI (EBRI). A multivariable competing risk analysis based on a proportional sub distribution hazards model was used to determine the impact of different radiotherapy modalities on BCa incidence and specific mortality. Results Incidence of BCa was significantly high in patients treated with EBRT, RI, and EBRI vs. RP [sub distribution hazard ratio (SHR) 1.41, P<0.001; SHR 1.58, P<0.001; SHR 1.56, P<0.001, respectively]. BCa following EBRT, RI, and EBRI were more commonly non-urothelial (3.3%, 2.9%, 3.3%, respectively, versus 1.2%) and T4 (3.5%, 6.1%, 5.0%, respectively, versus 1.6%) compared with RP. RI associated with a higher rate of BCa metastasis than RP (2.6% vs. 1.1%). Prior EBRT, RI, and EBRI increased BCa-SM (SHR 1.44, P=0.001; SHR 1.21, P=0.047; and SHR 1.42, P=0.032, respectively). Conclusions Patients receiving radiotherapy for PCa have a higher risk of BCa. BCa after EBRT, RI, and EBRI is more likely to be non-urothelial, stage T4, and with increased BCa-SM. Prior RI associated with a higher rate of BCa metastasis.