119 - Conventional vs. Hypofractionated, Radiotherapy for High-Risk Prostate Cancer: 10-Year Outcomes of the Randomized, Non-Inferiority, Phase 3 PCS5 Trial

03:20pm - 03:30pm PT

Room 24

Presenter(s)

Tamim Niazi, MD - McGill University, Montreal, QC

T. M. Niazi¹, A. Nabid², S. A. Tisseverasinghe³, R. Bettahar⁴, R. Dahmane⁵, A. G. Martin⁶, M. Jolicoeur⁷, M. Yassa⁸, M. Barkati⁹, L. Igidbashian¹⁰, B. Bahoric¹¹, R. Archambault¹², H. Villeneuve¹³, and M. Mohiuddin¹⁴; ¹McGill University, Montreal, QC, Canada, ²CIUSSS de l'Estrie - CHUS, Sherbrooke, QC, Canada, ³Department of Radiation Oncology, McGill University, Gatineau, QC, Canada, ⁴CSSS Rimouski-Neigette, Rimouski, QC, Canada, ⁵Hopital Universitaire de Trois Rivieres, Trois Rivieres, QC, Canada, ⁶CHU de Québec – Université Laval, Québec, QC, Canada, ⁷Charles LeMoin Hospital Montreal CA, Mondtreal C, QC, Canada, ⁸CIUSSS de L'Est-de-I'lle-de Montreal Hopital Maisonneuve-Rosemont, Montreal, QC, Canada, ⁹Département de radio-oncologie, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada, ¹⁰Département de radio-oncologie, Centre Intégré de Santé et de Services Sociaux de Laval, Laval, QC, Canada, ¹¹Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada, ¹²Centre Intégré de Santé et de Services Sociaux de l'Outaouais, Gatineau, QC, Canada, ¹³CSSS de Chicoutimi, Chicoutimi, QC, Canada, ¹⁴Saint John Regional Hospital and Dalhousie University, Saint John, NB, Canada

Purpose/Objective(s): The low a\ß ratio of prostate cancer (PCa), 1.5-2, suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of hypofractionated radiation treatment (HFRT). Prostate Cancer Study 5 (PCS5) is the first randomized trial of moderately HFRT in high-risk PCa patients treated with contemporary long term androgen deprivation therapy (ADT) and pelvic nodal radiation. We report the pre-planned analysis of efficacy at ten years.

Materials/Methods: PCS5 is a Canadian multi-centric, non-inferiority phase III trial of conventionally fractionated radiation therapy (CFRT) vs. HFRT in men with high-risk PCa as per NCCN definition. From Feb. 2012 to Mar. 2015, 329 patients were randomized in a 1:1 ratio to receive either CFRT or HFRT. All patients received neo-adjuvant, concurrent and adjuvant androgen suppression, with a median duration of 24 months. CFRT consisted of 76 Gy in 2 Gy per fraction to the prostate where 46 Gy was delivered to the pelvic lymph nodes. HFRT consisted of concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate and 45 Gy, in 1.8Gy per fraction to the pelvic lymph nodes. Participants were analyzed as per intention-to-treat.

Results: Of the 329 patients, 164 were randomized to HFRT and 165 to CFRT. Of these, 160 men in the hypofractionation arm and 160 in the standard arm were included in survival analyses. At 10 years of follow up there were no significant differences in survival outcomes between HFRT and CFRT for overall mortality (68.2% vs. 66%; RR 1.04 [0.87-1.25]; CI:95%; p=0.67), prostate cancer specific mortality (92.3% vs. 89.8%; RR 1.03 [0.94-1.13]; CI:95%; p=0.74), biochemical recurrence (82.7% vs. 82.4%; RR 1.01 [0.90-1.12]; CI:95%; p=0.85), distant recurrence free survival (87.8%-87.6%; RR 1.00 [0.91-1.10]; CI 95%; p=0.972) and distant metastases free survival, including metastases or death (64.1% vs. 64.2%; RR 1.01 [0.83-1.22]; CI:95%; p=0.96), respectively. The Relative Risks were close to 1.00 for all outcomes at 3-, 5-, 7- and 10 years after treatment, with very tight bootstrapped confidence intervals, suggesting equivalent risks for all outcomes in both study arms. There were no significant differences in grade 3 or higher acute and delayed genitourinary (GU) and gastrointestinal (GI) toxicities at 2 years and no new toxicities emerged thereafter at 10 year follow up. There were no grade 4 toxicities in either arm.

Conclusion: This is the first hypofractionated radiotherapy study in high-risk PCa patients treated with contemporary radiation and androgen suppression. Our 10 year results confirm that hypofractionated radiotherapy using 68 Gy in 25 fractions is non-inferior to conventional fractionation using 76Gy in 38 fractions and should be considered as a new standard of care for high risk prostate cancer patients planned to be treated with external-beam radiotherapy and long term ADT.