Impact of timing on salvage radiation therapy adverse events following radical prostatectomy: A secondary analysis of the RTOG 9601 cohort.

The use of adjuvant radiotherapy (RT) after radical prostatectomy (RP) is very limited in prostate cancer patients mainly due to concerns for worsening of functional outcomes with early delivery of RT. We sought to test the impact of timing between RP and RT on adverse events rate. Using the Radiation Therapy Oncology Group (RTOG) 9601 trial cohort, we performed post hoc analysis of 760 men with biochemical recurrence after RP, who received subsequent RT. Bowel adverse events (rectal urgency, diarrhea, and hematochezia); bladder adverse events (urinary frequency, dysuria, hematuria, and incontinence); and new onset of erectile dysfunction were documented as acute (<90 days after starting RT) or chronic, at each visit, per trial protocol. Regression analysis tested the impact of time between RP and RT on the aforementioned adverse events, after adjusting for potential confounders. The rate of acute bladder, acute bowel, late bladder, late bowel, and late impotence adverse events was, respectively, 49.3%, 60.9%, 61.2%, 48.8%, and 13.6% in patients with a time period between RP and RT ≤ 2.1 years (the median) vs. 47.5%, 63%, 59.1%, 47%, and 14.5% in patients with >2.1 years (all P > 0.5). At multivariable analysis, time from RP to RT was not an independent predictor of acute bladder (odds ratio [OR]: 1.002), acute bowel (OR: 1.024), chronic bladder (OR: 0.976), chronic bowel (OR: 1.023), and late impotence (OR: 1.031) adverse events (all P > 0.4). There was no impact of timing between RP and RT on urinary, bowel, and erectile adverse events related to RT. Thus, our RTOG 9601 post hoc analysis challenges the current belief that early postsurgical RT compromises functional outcomes more than late RT and support additional research to evaluate the perceived benefit in terms of adverse effects by prolonging the time between RP and RT.

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