Secondary Bladder Cancer After Prostate Cancer Treatment: An Age-matched Comparison Between Radiation and Surgery

Steven Monda; Manolis Pratsinis; Hansen Lui; Onika Noel; Thenappan Chandrasekar; Christopher P Evans; Marc A Dall'Era

doi:10.1016/j.euf.2023.09.002

Secondary Bladder Cancer After Prostate Cancer Treatment: An Age-matched Comparison Between Radiation and Surgery

Eur Urol Focus. 2023 Sep 16:S2405-4569(23)00199-2. doi: 10.1016/j.euf.2023.09.002. Online ahead of print.

Authors

Steven Monda¹, Manolis Pratsinis², Hansen Lui³, Onika Noel⁴, Thenappan Chandrasekar³, Christopher P Evans³, Marc A Dall'Era³

Affiliations

¹ Department of Urologic Surgery, University of California Davis, Sacramento, CA, USA. Electronic address: smonda@ucdavis.edu.
² Department of Urologic Surgery, University of California Davis, Sacramento, CA, USA; Department of Urology, St. Gallen Hospital, St. Gallen, Switzerland.
³ Department of Urologic Surgery, University of California Davis, Sacramento, CA, USA.
⁴ Department of Urologic Surgery, University of California Davis, Sacramento, CA, USA; Department of Urology, University of Texas Health San Antonio, San Antonio, TX, USA.

PMID: 37722954
DOI: 10.1016/j.euf.2023.09.002

Abstract

Background: Secondary malignancy is a long-term risk of radiation. External beam radiation therapy (EBRT) for prostate cancer treatment has been associated with later development of bladder cancer and worse bladder cancer features.

Objective: We sought to provide an updated comparison of the long-term risk of bladder cancer after different localized prostate cancer treatments.

Design, setting, and participants: Using the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we compared an age-matched subset of patients who underwent radical prostatectomy (RP) with those who underwent EBRT, brachytherapy (BT), EBRT + BT, and RP followed by EBRT (RPtoEBRT) between 2000 and 2018. Our final cohort included 261 609 patients with a median follow-up of 11.6 yr.

Outcome measurements and statistical analysis: Our primary outcomes were time to bladder cancer diagnosis, muscle-invasive bladder cancer diagnosis, and bladder cancer death. We used cause-specific hazard models considering death as a competing event. A similar analysis was performed on lung cancer, as a surrogate marker for smoking. We also compared proportions of variant histology, high-grade, and invasive disease among bladder cancers that occurred after radiation versus RP using chi-square testing.

Results and limitations: All radiation groups were associated with bladder cancer diagnosis; hazard ratios (HRs) were 1.72, 1.85, 1.80, and 1.53 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively, using RP as a referent (all p < 0.001). HRs for bladder cancer death were even higher: 2.39, 2.57, and 3.02 for EBRT, BT, and EBRT + BT, respectively (all p < 0.001), except for RPtoEBRT (HR 1.43, p = 0.28). Lung cancer diagnosis was also associated with radiation but at lower HRs-1.63, 1.32, 1.42, and 1.30 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively (all p < 0.001). There were a higher proportion of ≥T2, ≥T3, and sarcomatoid variant bladder cancers after radiation (all p < 0.01) CONCLUSIONS: The risk of developing and dying from bladder cancer is increased in patients treated with radiation compared with those treated with RP. The risk was similar for BT and EBRT. Bladder cancers after radiation are more likely to be sarcomatoid variant and present as muscle invasive.

Patient summary: We observed the rates of bladder cancer after patients had undergone surgery or radiation for prostate cancer, and found higher rates of bladder cancer after radiation. We also observed that bladder cancers that occur after radiation tend to be more aggressive.

Keywords: Bladder cancer; Brachytherapy; Epidemiology; External beam radiation therapy; Prostate cancer; Radiation; Secondary malignancy.