1764O - Timing of radiotherapy (RT) after radical prostatectomy (RP): Final results of RADICALS RT randomised controlled trial

Background

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).

Methods

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.

Results

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).

Conclusions

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.

Clinical trial identification

NCT00541047.

Editorial acknowledgement

None

Legal entity responsible for the study

UCL.

Funding

No companies involved.

Disclosure

C. Parker: Financial Interests, Personal, Advisory Board: ITM Radiopharma; Financial Interests, Institutional, Advisory Board: AAA. N. Clarke: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer. W. Cross: Financial Interests, Personal, Advisory Board: Janssen, Bayer. C. Catton: Financial Interests, Institutional, Funding: Canadian Cancer Trials Group, AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer, AbbVie, Janssen, Astellas. H.A. Payne: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Ferring, Ipsen. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Sanofi, Pfizer, Myovant, Novartis, AstraZeneca, Merck, Myovant; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. H. Lindberg: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer, Sanofi-Aventis, Roche; Non-Financial Interests, Personal, Other: Janssen, Astellas, Bayer, Sanofi-Aventis. A. Zarkar: Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Advisory Board: Astellas, Amgen, Pfizer, EUSA Pharma. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL; Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis; Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London; Non-Financial Interests, Advisory Role, rEECur: University of Birmingham; Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen; Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly; Financial Interests, Personal, Other, Educational lecture not associated with any products: Eisai; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. All other authors have declared no conflicts of interest.