Evaluating the Impact of Prostate Only Versus Pelvic Radiotherapy for Pathological Node-positive Prostate Cancer: First Results from the Multicenter Phase 3 PROPER Trial

Background: The optimal treatment for patients with pathological node-positive (pN1) prostate cancer (PCa) is unclear.Objective: To evaluate whether whole-pelvis radiotherapy (WPRT) improves clinical relapse-free survival (cRFS) in comparison to prostate-only radiotherapy (PORT) in pN1 PCa.Design, setting, and participants: PROPER was a phase 3 trial randomizing patients to WPRT or PORT. All patients had pN1cM0 PCa with fewer than five lymph nodes involved.Intervention: All patients underwent pelvic lymph node dissection followed by radical prostatectomy/primary radiotherapy + 2 yr of androgen deprivation therapy (ADT). Patients were randomized to PORT (arm A) or WPRT (arm B).Outcome measurements and statistical analysis: The primary outcome was cRFS. The sec-ondary endpoints were overall survival (OS), biochemical relapse-free survival (bRFS), and toxicity. The study was stopped because of poor accrual in June 2021 after the inclu-sion of 69 patients. We report on OS, bRFS, cRFS, and acute and late toxicity.Results and limitations: The median follow-up was 30 mo in arm A (n = 33) and 36 mo in arm B (n = 31). The 3-yr OS rate was 92% +/- 5% in arm A and 93% +/- 5% in arm B (p = 0.61). None of the patients died of PCa. The 3-yr bRFS was 79% +/- 9% in arm A and 92% +/- 5% in arm B (p = 0.08). The 3-yr cRFS rate was 88% +/- 6% in arm A and 92% +/- 5% in arm B (p = 0.31). No pelvic recurrence was observed in arm B. Acute grade 2 gastrointestinal toxicity was higher with WPRT (15% in arm A vs 45% in arm B; p = 0.03). Limitations are the early closure because of poor accrual and the limited follow-up. Conclusions: The results of our trial are hypothesis-generating but add evidence sup-porting the recommendation to offer WPRT to patients with pN1 PCa. However, WPRT is associated with more acute gastrointestinal toxicity.Patient summary: We looked at the impact of radiotherapy to the whole pelvis (WPRT) for patients with prostate cancer that had spread to the lymph nodes. Although the trial was closed early because of poor enrolment, we found that WPRT improves survival free from relapse, and no recurrences were observed in the pelvis. WPRT is associated with more acute side effects on the gastrointestinal system in comparison to radiotherapy to just the prostate.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).