Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Abstract

Background The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer is uncertain. The RADICALS-RT trial compared the efficacy and safety of adjuvant RT versus an observation policy with salvage RT for PSA failure. Methods RADICALS-RT is a randomised controlled trial enrolling patients with≥1 risk factor (pT3/4, Gleason 7-10, positive margins or pre-op PSA≥10ng/ml) for recurrence after radical prostatectomy. Patients were randomised in a 1:1 ratio to adjuvant RT (“Adjuvant RT”) or an observation policy with salvage RT for PSA failure (PSA≥0.1ng/ml or 3 consecutive rises) (“Salvage RT”). Stratification factors were Gleason score, margin status, planned RT schedule (52.5Gy/20 fractions or 66Gy/33 fractions) and centre. The primary outcome measure was freedom-from-distant metastases, designed with 80% power to detect an improvement from 90% with Salvage RT (control) to 95% at 10yr with Adjuvant RT. We report on bPFS, freedom-from-non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; HR<1 favours Adjuvant RT. Trial registration: NCT00541047. Findings Between Oct 2007 and Dec 2016, 1396 patients from United Kingdom, Denmark, Canada and Ireland were randomised, 699 Salvage RT and 697 Adjuvant RT. Allocated groups were balanced with median age 65yr. Median follow-up is 4.9yr. 93% (649/697) Adjuvant RT reported RT within 6m; 33% (228/699) Salvage RT reported RT within 8yr after randomisation. With 169 events, 5yr bPFS was 85% for Adjuvant RT and 88% for Salvage RT: HR=1·10 (95%CI 0·81-1·49, p=0·56). Freedom-from-non-protocol hormone therapy at 5yr was 92% vs 94% (HR=1·24, 95%CI 0·76-2·01, p=0.39). Self-reported urinary incontinence was worse at 1yr for Adjuvant RT: 5·3% vs 2·7% (p=0·008). Grade 3-4 urethral stricture within 2yr was reported in 6% Adjuvant RT vs 4% Salvage RT (p=0·02). Interpretation First results from RADICALS-RT do not support routine administration of adjuvant RT after radical prostatectomy. Adjuvant RT increases the risk of urinary morbidity. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy.