1764O Timing of Radiotherapy (RT) after Radical Prostatectomy (RP): Final Results of RADICALS RT Randomised Controlled Trial

The optimal timing of RT after RP for prostate cancer is uncertain. RADICALS-RT compared the efficacy and safety of adjuvant RT (aRT) versus an observation policy with salvage RT for early PSA failure (Obs+sRT). We previously reported an early outcome measure (OM): bPFS, and now have enough events to report on the primary OM, freedom from distant metastases (FFDM). Patients with post-op PSA≤0.2ng/ml and ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, or pre-op PSA≥10ng/ml) were randomised ≤22wk after RP to aRT or Obs+sRT for PSA failure: PSA ≥0.1ng/ml or 3 consecutive rises. Stratification factors were Gleason score, margin status, planned RT volume (prostate bed only, prostate bed + pelvis), RT schedule (52.5Gy/20f, 66Gy/33f) and centre. The primary OM was FFDM with >1200 pts needed for 80% power to detect an improvement from 90% to 95% at 10yr with aRT. Secondary OMs include overall survival, safety & patient reported OMs (1, 5, 10yr). Standard survival analysis methods were used. 1396 pts were randomised (697 aRT, 699 Obs+sRT) from Oct-2007 to Dec-2016 (82% UK, 13% Denmark, 4% Canada, 1% Ireland). Median age was 65yrs and 37% (517/1396) had a CAPRA-S score of 6+. Data were frozen May 2022 and median follow-up was 8yrs. 93% (650/697) aRT started RT within 5mo; 39% (270/699) Obs+sRT started RT. Median PSA at time of sRT was 0.2ng/ml. 24% (156/650) aRT and 27% (72/270) Obs+sRT reported HT with their RT. With 80 events, FFDM at 10 yrs was 93% for aRT v 90% for Obs+sRT (HR= 0.68 (95%CI 0·43-1·07, p=0·095). Overall survival at 10-yrs was 88% vs 87% (HR=0.98 (95%CI 0.67 to 1.44, p=0.92). Self-reported urinary incontinence and faecal incontinence were worse at 1yr for aRT (p<0.001). RADICALS-RT is the largest study ever conducted addressing the value of adjuvant RT in prostate cancer. Final results from RADICALS-RT show no evidence of a meaningful benefit for aRT after RP in this patient group. Adjuvant RT increases risk of urinary & bowel morbidity. An observation policy with salvage RT for PSA failure should be the current standard after RP.