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

Abstract

BackgroundLong-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. ObjectiveTo investigate the impact of RP and EBRT on subsequent risk of developing bladder (BCa) and/or rectal cancer (RCa) among PCa survivors. Design, setting, and participantsA 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. Outcome measurements and statistical analysisMultivariable competing-risk regression analyses were performed to assess the risk of developing a second primary BCa or RCa. Results and limitationsOf 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<0.001), but not RCa (p=0.4). Limitations include lack of information regarding the dose of radiotherapy and the retrospective nature with the implicit risk of selection bias. ConclusionsPatients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. These results need to be validated in a well-designed randomized prospective trial. Patient summaryWe retrospectively analyzed the risk of developing a second primary bladder or rectal cancer during follow-up for patients treated with radical prostatectomy or external beam radiotherapy for a localized prostate cancer. We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor.