BACKGROUND: 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.
OBJECTIVE: To 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 PARTICIPANTS: 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.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing-risk 
regression analyses were performed to assess the risk of developing a second 
primary BCa or RCa.
RESULTS AND LIMITATIONS: 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.
CONCLUSIONS: 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.
PATIENT SUMMARY: 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.