Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy

Purpose Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Methods and Materials Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Results Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Conclusions Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone. The highest increased risk of urinary toxicity occurs within the 2 years after therapy and then declines to an approximately 1% increase in incidence per year.