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<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.

Patients 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.

We 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.

European urology. 2018 Oct 04 [Epub ahead of print]

Marco Moschini, Emanuele Zaffuto, Pierre I Karakiewicz, David D Andrea, Beat Foerster, Mohammad Abufaraj, Francesco Soria, Agostino Mattei, Francesco Montorsi, Alberto Briganti, Shahrokh F Shariat

Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy; Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland. Electronic address: ., Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy; Department of Urology, University of Montreal, Montreal, Quebec, Canada., Department of Urology, University of Montreal, Montreal, Quebec, Canada., Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria., Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan., Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland., Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy., Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.