Evaluation of clinical risk stratification to determine benefit from long-term versus short-term androgen deprivation in high-risk localized prostate cancer.

Background: Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT).

Methods: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials. The key outcomes of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis (TTM) and prostate cancer-specific mortality (PCSM). Stratified Cox and Gray's regression were used to obtain the overall treatment effect for outcomes and risk groups, and the Wald interaction test to estimate whether treatment benefit differed by risk group or trial. Heterogeneity of studies was assessed by Cochran's Q and I².

Results: 2780 patients from 3 trials were included. Patients with very-high risk disease had greater benefit with ltADT compared to high-risk disease (MFS HR 0.77 [0.68-0.88] vs. 0.89 [0.76-1.03]; TTM 0.61 [0.51-0.74] vs. 0.77 [0.59-0.99]; PCSM 0.71 [0.56-0.90] vs. 0.82 [0.59-1.14]; OS 0.87 [0.76-1.00] vs. 0.93 [0.79-1.08]), but there was no statistically significant difference in treatment effect by risk group (p-interaction >0.1). Heterogeneity for treatment effect across trials was low in the very high-risk group and moderate in the high-risk group.

Conclusions: Clinical risk stratification merits further evaluation in clinical trials to identify which patients with HRLPC may benefit from ltADT versus stADT.