Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials

The Prostate Subtyping Classifier is both a prognostic and a predictive biomarker in patients with high-risk localized prostate cancer undergoing radiotherapy. In addition to improving risk prediction, this classifier also allows physicians to select which patients will benefit from prolonged androgen deprivation therapy. Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24–28 mo) versus short-term (ST; 4 mo) ADT. Biopsy samples from three randomized, phase 3 trials–NRG/RTOG 9202, 9413, and 9902–were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models. On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3–2.5], p