PACE-A: An international phase 3 randomised controlled trial (RCT) comparing stereotactic body radiotherapy (SBRT) to surgery for localised prostate cancer (LPCa)—Primary endpoint analysis.

Authors

null

Nicholas John Van As

The Royal Marsden NHS Foundation Trust/Institute of Cancer Research, United Kingdom, London, United Kingdom

Nicholas John Van As , Alison Tree , Peter James Ostler , Hans van der Voet , Daniel Ford , Shaun Tolan , Paula Wells , Rana Mahmood , Mathias Winkler , Andrew Chan , Alan Thompson , Christopher Ogden , Stephanie Brown , Julia Pugh , Stephanie M. Burnett , Clare Griffin , Jaymini Patel , Olivia Naismith , Emma Hall

Organizations

The Royal Marsden NHS Foundation Trust/Institute of Cancer Research, United Kingdom, London, United Kingdom, The Royal Marsden NHS Foundation Trust/Institute of Cancer Research, London, United Kingdom, Mount Vernon Hospital, Dunstable, United Kingdom, The James Cook University Hospital, Middlesbrough, United Kingdom, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom, St Bartholomew's Hospital, London, United Kingdom, Colchester General Hospital, Colchester, United Kingdom, Charing Cross Hospital, London, United Kingdom, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, United Kingdom, The Royal Marsden NHS Foundation Trust, London, United Kingdom, Institute of Cancer Research, London, United Kingdom, The Institute of Cancer Research, London, United Kingdom, Radiotherapy Trials Quality Assurance (RTTQA), Royal Marsden NHS Foundation Trust, London, United Kingdom, The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom

Research Funding

Pharmaceutical/Biotech Company
Accuray, The Royal Marsden Cancer Charity, Varian

Background: People presenting with early-stage LPCa have several treatment options. There is therapeutic equipoise with lack of randomised evidence for superiority of radiotherapy or surgery. PACE-A aimed to determine if there is improved quality of life (QoL) following SBRT compared to surgery. Methods: PACE (NCT01584258) is a phase 3 open-label multiple-cohort RCT. In PACE-A, people with LPCa, T1-T2, Gleason≤3+4, PSA≤20ng/mL & suitable for surgery were randomised (1:1) to SBRT or surgery. SBRT dose was 36.25Gy/5 fractions in 1-2 weeks; surgery was laparoscopic or robotically assisted prostatectomy. Androgen deprivation was not permitted. Co-primary endpoints were patient reported outcomes (PROs) of Expanded Prostate Index Composite (EPIC-26) questionnaire number of absorbent pads per day & EPIC bowel subdomain score at 2 years. Target sample size was 234 participants (pts) to detect 9% difference in urinary incontinence (80% power, 5% 2-sided alpha) & 5-point difference in mean bowel subdomain score (90% power, 5% 2-sided alpha) with higher EPIC score (range 0-100) indicating better QoL. Secondary endpoints included clinician reported toxicity and additional PROs (1% significance level). Analysis is by treatment received. Results: From Aug 2012 to Feb 2022, 123 men from 10 UK centres were randomised. The IDMC advised stopping recruitment after a 2-year gap in during COVID. Pts had median age 66years (IQR: 61, 69), median PSA 8ng/ml (6, 11) with 52% tumours ≥T2b and 79% Gleason 3+4; 93% pts were of white race. 58/63 pts received SBRT as allocated (2 received surgery, 2 unknown, 1 withdrawn); 48/60 received surgery as allocated (1 received SBRT, 3 received CRT, 2 unknown, 6 withdrawn). 8 laparoscopic and 42 robotic assisted operations were performed. Median follow-up is 50 months (IQR 41, 74). At 2 years, fewer SBRT pts reported use of urinary pads: 2/43 (4.5%) vs 15/32 (46.9%), p<0.001. SBRT pts had significantly worse bowel subdomain score (mean (SD) 88.4 (12.7) vs 97.3 (5.5), p<0.001). 7/45 (15.6%) SBRT and 0/31 (0%) surgery pts reported moderate/big problem with bowel symptoms (p=0.04). SBRT pts reported less EPIC sexual subdomain score (58.0 (31.9) vs 29.3 (20.5), p<0.001); there was no evidence of a difference in urinary subdomain score (85.5 (19.8) vs 80.5 (20.8), p=0.29). At 2 years, CTCAE genitourinary grade 2 or higher(G2+) toxicity was seen in 5/54 (9.3%) SBRT vs 4/42 (9.5%) surgery pts (p=0.97); there was no G2+ gastrointestinal (GI) events seen in either group. Conclusions: PACE-A contributes the first randomised data to the comparison of SBRT with surgery in LPCa providing PRO data relevant to informed decision making. Compared to surgery, pts receiving SBRT had better urinary continence & sexual bother score; clinician reported GI toxicity was low but SBRT pts reported more bowel bother at 2 years. Clinical trial information: NCT01584258.

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

General Session

Session Title

Clinical Decision-Making in the Treatment of Localized Prostate Cancer: Controversial Points

Track

Prostate Cancer

Sub Track

Symptoms, Toxicities, Patient-Reported Outcomes, and Whole-Person Care

Clinical Trial Registration Number

NCT01584258

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 298)

DOI

10.1200/JCO.2023.41.6_suppl.298

Abstract #

298

Abstract Disclosures