Dose Escalated Radiotherapy Alone or in Combination With Short-Term Androgen Suppression for Intermediate Risk Prostate Cancer: Outcomes From the NRG Oncology/RTOG 0815 Randomized Trial
Androgen suppression can improve outcomes when added to radiotherapy (RT) for intermediate risk prostate cancer, but no study to date has reported its utility in the context of contemporary, dose-escalated RT. Herein, the clinical outcomes of a phase III prospective trial evaluating the utility of total androgen suppression (TAS) combined with dose-escalated RT for patients with intermediate risk prostate cancer are reported.
Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of the following risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA value > 10 and ≤ 20 ng/mL. Patients with all three risk factors and ≥ 50% of biopsy cores positive were ineligible. After stratification by number of intermediate risk factors (single vs. multiple), RT boost modality, and baseline comorbidity (ACE-27 comorbidity index ≥ vs. < grade 2), patients were randomized to dose-escalated RT alone (Arm 1) or combined with TAS (Arm 2) consisting of LHRH agonist/antagonist in combination with oral antiandrogen for a duration of 6 months. Permitted RT modalities were external beam radiotherapy (EBRT) alone to total dose 79.2 Gy or EBRT (45 Gy) combined with LDR or HDR brachytherapy boost. Pelvic nodal RT was not permitted. Under a 1-sided significance level of 0.025 and 85% power, the study was designed to detect an improvement in the 5-year overall survival rate from 90% (Arm 1) to 93.3% (Arm 2). Patient reported quality of life outcomes were collected and are reported in another abstract.
The study completed its accrual objective. Between 2009 and 2016, 1538 patients were randomized. There were 750 eligible patients on Arm 1 and 742 on Arm 2 comprising the modified intent-to-treat population. 67% had a single intermediate risk factor. 88% were treated with EBRT with the remainder receiving EBRT plus brachytherapy boost. 33% had an ACE-27 score ≥ grade 2. With a median follow up of 6.2 years, 219 deaths occurred, 119 in Arm 1 and 100 in Arm 2, yielding 5-year overall survival estimates of 90% vs. 91%, respectively [HR 0.85 (95% CI 0.65-1.11); P = 0.22]. 193 patients experienced PSA failure, 125 in Arm 1 and 68 in Arm 2 [HR 0.52 (0.39-0.70); P < 0.001]. 35 patients developed distant metastases, 28 in Arm 1 and 7 in Arm 2 [HR 0.25 (0.11-0.57); P < 0.001]. 11 deaths were attributed to prostate cancer, 10 in Arm 1 and 1 in Arm 2 [HR 0.10 (0.01-0.80); P = 0.007]. One hundred three acute grade ≥ 3 adverse events occurred, 17 (2.3%) in Arm 1 and 86 (17.5%) in Arm 2 ( P < 0.001). The cumulative incidence of late grade ≥ 3 adverse events was 16.2% in Arm 1 and 17.5% in Arm 2 ( P = 0.27).
While the addition of TAS to dose-escalated RT did not improve overall survival for men with intermediate risk prostate cancer, significant improvements in rates of metastases, deaths due to prostate cancer, and PSA failures support the continued use of combination dose-escalated RT and TAS. Benefits will need to be weighed against the increased risk of adverse events and the patient reported outcomes analysis.
Krauss DJ, Karrison TG, Martinez AA, Morton G, Yan D, Bruner DW, et al. Dose escalated radiotherapy alone or in combination with short-term androgen suppression for intermediate risk prostate cancer: outcomes from the NRG Oncology/RTOG 0815 randomized trial. Int J of Radiat Oncol Biol Phys 2021 Nov 1;111(3): S1.