To identify patients with intermediate risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiotherapy (DERT), we performed a secondary analysis of a phase III trial by measuring biochemical failure (BF), distant metastases (DM), prostate cancer specific mortality (PCSM), overall survival (OS) and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF).
The initial trial randomized 600 patients with IRPC to a three-arm trial with 200 patients per arm consisting of 6 months of ADT plus RT 70Gy (ADT+RT70) vs. ADT plus a DERT of 76Gy (ADT+DERT76) vs. DERT of 76Gy alone (DERT76). We performed an analysis based on IRF present: clinical stage, PSA level, Gleason score, percentage of positive biopsy cores (PBC) ≥50% and Gleason pattern. Patients were allocated into two groups: favorable intermediate risk (FIR), defined as patients with only one IRF without Gleason pattern 4+3 or PBC ≥50% and unfavorable intermediate risk (UIR) all other patients. BF, DM, PCSM, OS and DMFS were compared between FIR and UIR.
The median follow-up is 11.3 years (interquartile range: 10.9-11.7). In the FIR cohort, BF and OS were not significantly different between arms. UIR patients had significantly worse DMFS [Hazard ratio (95% confidence interval) = 1.61 (1.20-2.15), p=0.026] and OS [HR=1.51 (1.12 - 2.04), p=0.0495] and a non-significant higher cumulative incidence of BF rate [1.55 (0.98-2.47), p=0.08]. In UIR patients a significant improvement in BF was seen in the arms receiving ADT compared to DERT76 alone. On multivariable analysis, Gleason pattern 4+3 and PSA >10 ng/ml independently impacted on BF and OS, regardless of the treatment arm.
In IRPC, therapeutic optimization appears possible. To avoid ADT side effects, DERT76 alone appears sufficient in patients harboring only one RF without Gleason pattern 4+3 and PBC ≥50% (FIR). All other UIR patients seem to benefit from ADT + DERT76.
International journal of radiation oncology, biology, physics. 2021 Apr 23 [Epub ahead of print]
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
Centre Hospitalier Universitaire de Sherbrooke, CA. Electronic address: ., Centre Hospitalier Universitaire de Sherbrooke, CA., Centre Hospitalier Universitaire de Québec, CA., Centre Hospitalier Universitaire de Montréal, CA., Hôpital Maisonneuve-Rosemont de Montréal, CA., Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean, CA., Hôpital Général Juif de Montréal, CA., Hôpital de Gatineau, CA., Centre Hospitalier Régional de Trois-Rivières, CA., Centre Hospitalier Régional de Rimouski, CA., Nova Scotia Cancer Center, NS., McGill University Health Centre, CA.