External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis

Long-term survival can be achieved in patients affected by localized prostate cancer (PCa) treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). However, development of a second primary tumor is still poorly investigated. To investigate the impact of RP and EBRT on subsequent risk of developing bladder (BCa) and/or rectal cancer (RCa) among PCa survivors. A total of 84397 patients diagnosed with localized PCa, treated with RP or EBRT between 1988 and 2009, and older than 65 yr of age were identified in the Surveillance, Epidemiology, and End Results Medicare insurance program-linked database. Our primary objective was to investigate the effect of EBRT and RP on the second primary BCa and RCa incidence. Multivariable competing-risk regression analyses were performed to assess the risk of developing a second primary BCa or RCa. Of the 84397 individuals included in the study, 33252 (39%) were treated with RP and 51145 (61%) with EBRT. Median follow-up was 69 months, and follow-up periods for patients who did not develop BCa, RCa, or pelvic cancer were 68, 69, and 68 mo, respectively. A total of 1660 individuals developed pelvic tumors (1236 BCa and 432 RCa). The 5- and 10-yr cumulative BCa incidence rates were 0.75% (95% confidence interval [CI]: 0.64–0.85%) and 1.63% (95% CI: 1.45–1.80%) versus 1.26% (95% CI: 1.15–1.37%) and 2.34% (95% CI: 2.16–2.53%) for patients treated with RP versus EBRT, respectively. The 5- and 10-yr cumulative RCa incidence rates were 0.32% (95% CI: 0.25–0.39%) and 0.73% (95% CI: 0.61–0.85%) versus 0.36% (95% CI: 0.30–0.41%) and 0.69% (95% CI: 0.60–0.79%) for patients treated with RP versus EBRT, respectively. On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18–1.55; p