Abstract 1381P
Background
Prospective reports suggest metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) is associated with improved treatment outcomes. When the addition of androgen-deprivation therapy (ADT) to MDT for omCSPC is needed is unclear. Here we assess the ability of an androgen receptor activity (AR-A) signature to provide prognostic information for omCSPC patients treated with MDT without and with ADT.
Methods
The MDT treatment cohort consisted of patients enrolled on STOMP and ORIOLE trials and similar patients from a retrospective cohort also treated with MDT+/- ADT. RNA next generation sequencing (NGS) was performed on primary prostate tumors from the cohort and AR-A scores were determined. The primary endpoint was time to castration-resistant prostate cancer (ttCRPC). The Kaplan-Meier method and log-rank test were used to assess differences when patients were stratified by median and continuous AR-A score and treatment group. Cox proportional hazard regressions were fit to calculate hazard ratios (HR) and assess the prognostic value of AR-A scores. Our secondary endpoint was proportion of cell types based on PAM50 subtyping.
Results
84 patients were included with median follow-up of 43 months. 5-year ttCRPC was lower with MDT+ADT (3.2%) vs MDT (21.5%) with a pooled HR 0.42 (95% CI, 0.05 – 3.39, p=0.42). Overall, the AR-A was prognostic, in those with high AR-A the 5-year ttCRPC rates were 11.8% vs 33.2% with low AR-A (HR of 0.19, p=0.031). The continuous AR-A scores were also prognostic with HR 0.81 (p=0.023). Patients with high AR-A treated with MDT vs MDT+ADT had similar 5-year ttCRPC (0% vs 11.6%, p=0.289), but there was a significant benefit to the addition of ADT in patients with low AR-A treated with MDT (0% vs 41.9%, p=0.048). PAM50 demonstrated 12% luminal A, 73% luminal B and 15% basal subtypes.
Conclusions
An AR-A signature is prognostic for outcomes in omCSPC treated with MDT and this study suggests that high AR-A patients might derive less benefit from the addition of ADT to MDT. Further validation is needed to optimize omCSPC patient selection for treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Phuoc Tran.
Funding
Anonymous donor, Movember Foundation-Distinguished Gentlemen’s Ride-Prostate Cancer Foundation, Babara's Fund, National Capitol Cancer Research Fund.
Disclosure
P.T. Tran: Financial Interests, Personal, Advisory Board: J&J, RefleXion Medical Inc. A. Hakansson, S. Liu, E. Davicioni: Financial Interests, Personal, Full or part-time Employment: Veracyte. P. Ost: Financial Interests, Personal, Research Grant: Bayer. All other authors have declared no conflicts of interest.