118 - Phase III Study of Hypofractionated, Dose Escalation Radiotherapy vs. Conventional Pelvic Radiation Therapy followed by High Dose Rate Brachytherapy Boost for High Risk Adenocarcinoma of the Prostate (PCS VI)
Presenter(s)
T. M. Niazi1,2, F. Vincent3, M. Jolicoeur4, J. Yousuf5, G. Delouya6, A. G. Martin7, M. Duclos8, M. I. Lock9, B. Bahoric10, A. Kamran11, R. Archambault12, A. Amjad13, and A. Nabid14; 1McGill University, Montreal, QC, Canada, 2Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada, 3Centre hospitalier regional de Trois-Rivieres, Trois-Rivieres, QC, Canada, 4Charles LeMoin Hospital Montreal CA, Mondtreal C, QC, Canada, 5Windsor Regional Hospital Cancer Program, Windsor, ON, Canada, 6Département de radio-oncologie, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada, 7CHU de Québec – Université Laval, Québec, QC, Canada, 8Cedars Cancer Center, Montreal, QC, Canada, 9Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada, 10Jewish General Hospital, Montreal, QC, Canada, 11Eastern Health Cancer Care Program, St. John''s, NL, Canada, 12Centre Intégré de Santé et de Services Sociaux de l'Outaouais, Gatineau, QC, Canada, 13Allan Blair Cancer Centre, Regina, SK, Canada, 14CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada
Purpose/Objective(s): The low a\ß ratio of 1.2-2 for prostate cancer (PCa) suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of lager fraction size. We have recently shown (PCS5) that high risk prostate cancer patients can safely and effectively be treated with moderate hypofractionated radiation therapy (HF-RT) using 68gy/25 fractions. To date there has been no phase-III randomized clinical-trial comparing moderately HF-RT with EBRT and HDR boost (HDRB). We are reporting on the primary endpoint, delayed toxicity, of EBRT+HDRB compared to moderate HFRT in this Canadian phase III trial: Prostate Cancer Study 6 (PCS6).
Materials/Methods: From January 2015–June 2022, 308 high-risk localized PCa patients were randomized to receive either HF-RT or EBRT+HDRB. All patients received neo-adjuvant, concurrent, and long-term adjuvant androgen deprivation therapy (ADT). EBRT+HDRB consisted of 46Gy in 2 Gy per fraction to the pelvis and a 15 Gy in one fraction HDR boost within 3 weeks of EBRT. HF-RT include concomitant dose escalation of 68Gy in 2.72Gy per fraction to the prostate, and 45Gy in 1.8Gy per fraction to the pelvic lymph-nodes.
Results: Of the 308 patients, 155 patients were treated with HF-RT and 145 with EBRT+HDRB. Eight patients were excluded for different reasons. In both intention to treat and as treated analysis, using log-Rank, there were more grade 1 or worse (G1+) and Grade 2 or worse (G2+) delayed GI events in the HF-RT than HF-RT. As treated analysis the delayed G1+ and G2+ GI events were 83/155 vs 56/145 (53.5% vs. 38.62%; 95% p=0.01) and 20/155 vs 10/145 (13% vs. 7%; p=0.05), respectively for HF-RT and EBRT+HDRB. When adjusted for smoking, diabetes and blood pressure, the difference in late GI G1+ and G2+ persisted with a HR of 1.74 (95% CI [1.23-2.46] p<0.001) for G1+ delayed GI toxicities and a HR of 2.14 (95% CI [1.00-4.59] p=0.05) for G2+ delayed GI toxicities, favoring EBRT+HDRB. There were no differences in G1+ or G2+ delayed GU toxicities between the arms. There were only few G3 GI toxicities in both arms and no grade 4-toxicities were reported.
Conclusion: This is the first study of EBRT+HDRB compared to moderate HF dose escalated RT in high-risk prostate cancer patients treated with long-term ADT and pelvic RT. Our results demonstrate that both treatment approaches are well-tolerated and that EBRT+HDRB carries less G1+ and G2+ delayed GI toxicities.