Timing of Radiotherapy (RT) after Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]

Background The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for PSA failure. Methods RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, pre-op PSA≥10ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT (“Adjuvant-RT”) or an observation policy with salvage RT for PSA failure (“Salvage-RT”) defined as PSA≥0.1ng/ml or 3 consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5Gy/20 fractions or 66Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant metastasis, designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10yr with Adjuvant-RT. Secondary outcome measures were bPFS, freedom-from-non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; HR<1 favours Adjuvant-RT. Findings Between Oct-2007 and Dec-2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with median age 65yr. 93% (649/697) Adjuvant-RT reported RT within 6m after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10yr FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 (95%CI 0·43–1·07, p=0·095). Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95%CI 0.667–1.440, p=0.917). Adjuvant-RT reported worse urinary and faecal incontinence one year after randomisation (p=0.001); faecal incontinence remained significant after ten years (p=0.017). Interpretation Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy