Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Abdenour Nabid; Nathalie Carrier; Eric Vigneault; Thu Van Nguyen; Peter Vavassis; Marc-André Brassard; Boris Bahoric; Robert Archambault; François Vincent; Redouane Bettahar; Derek Wilke; Luis Souhami

doi:10.1016/j.ejca.2020.10.023

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Eur J Cancer. 2021 Jan:143:64-74. doi: 10.1016/j.ejca.2020.10.023. Epub 2020 Dec 3.

Authors

Affiliations

¹ Centre Hospitalier Universitaire de Sherbrooke, CA, Canada. Electronic address: abdenour.nabid@usherbrooke.ca.
² Centre Hospitalier Universitaire de Sherbrooke, CA, Canada.
³ Centre Hospitalier Universitaire de Québec, CA, Canada.
⁴ Centre Hospitalier Universitaire de Montréal, CA, Canada.
⁵ Hôpital Maisonneuve-Rosemont de Montréal, CA, Canada.
⁶ Centre Intégré Universitaire de Santé et de Services Sociaux Du Saguenay-Lac-Saint-Jean, CA, Canada.
⁷ Hôpital Général Juif de Montréal, CA, Canada.
⁸ Hôpital de Gatineau, CA, Canada.
⁹ Centre Hospitalier Régional de Trois-Rivières, CA, Canada.
¹⁰ Centre Hospitalier Régional de Rimouski, CA, Canada.
¹¹ Nova Scotia Cancer Center, NS, Canada.
¹² McGill University Health Centre, CA, Canada.

PMID: 33279855
DOI: 10.1016/j.ejca.2020.10.023

Abstract

Background: The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone.

Methods: From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria.

Findings: With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity.

Interpretation: In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.

Keywords: Androgen deprivation therapy; Prostate cancer; Radiotherapy; Randomised trial.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Androgen Antagonists / pharmacology
Androgen Antagonists / therapeutic use*
Humans
Male
Middle Aged
Prospective Studies
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / radiotherapy*

Substances

Androgen Antagonists

Associated data

ClinicalTrials.gov/NCT00223145