Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

Shawn Malone 1 2, Soumyajit Roy 1 3, Libni Eapen 1 2, Choan E 1 2, Robert MacRae 1 2, Gad Perry 1 2, Julie Bowen 4, Rajiv Samant 1 2, Scott Morgan 1 2, Julia Craig 1, Kyle Malone 2, Scott Grimes 1

Main idea: In our study, there was no statistically significant difference in biochemical relapse-free survival between the two treatment groups. Similarly, no difference was seen in overall survival or late radiotherapy -related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term androgen-deprivation therapy with dose-escalated prostate radiotherapy are reasonable standards of care for localized prostate cancer.

Abstract

Purpose: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT).

Patients and methods: Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test.

Results: Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS (P = .10) or OS (P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%).

Source NIH