Bladder cancer is the most common other malignancy in men treated for prostate cancer [1]. A proportion of this bladder cancer is likely attributable to radiation treatment for prostate cancer. Radiation causes DNA double-strand breaks and has highly been associated with bladder cancer development among atomic bomb survivors [2]. The association between external beam radiation therapy (EBRT) and bladder cancer in men treated for prostate cancer compared with control patients undergoing radical prostatectomy (RP) has been established in several series [3], [4], [5], [6], [7]. Limited data also support a greater proportion of high-grade and advanced-stage bladder cancers after EBRT [8], [9]. The association between bladder cancer and brachytherapy (BT) is less clear [4], [10]. Further, comorbidity differences, especially age and smoking status, confound comparisons between radiation patients and surgical controls, and require special attention in analysis [11].

We sought to provide an updated, longer follow-up, age-matched, comparative analysis on the risk of bladder cancer after different prostate cancer treatment modalities. We assessed the risk of bladder cancer by comparing several radiation treatments to a surgical control, RP. Our radiation treatment arms included EBRT, BT, EBRT + BT, and RP followed by EBRT (RPtoEBRT). The RPtoEBRT arm was included to address the comorbidity differences inherent to the cohorts; the RPtoEBRT patients were hypothesized to be healthy enough to be considered for RP and likely later required EBRT for oncologic purposes. To also address our limited access to patient’s comorbidities, particularly smoking status, we performed a parallel analysis on lung cancer after prostate cancer treatment as a control smoking-related malignancy that was out of the field of pelvic radiation.