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PD27-06 NOVEL ANDROGEN RECEPTOR RECURRING SPLICE JUNCTIONS IN PROSTATE CANCER PREDICTS RESPONSE TO ABIRATERONE AND OVERALL SURVIVAL IN METASTATIC PROSTATE CANCER
Abstract   Peer reviewed

PD27-06 NOVEL ANDROGEN RECEPTOR RECURRING SPLICE JUNCTIONS IN PROSTATE CANCER PREDICTS RESPONSE TO ABIRATERONE AND OVERALL SURVIVAL IN METASTATIC PROSTATE CANCER

Kendrick Yim, Alyssa Obermeyer, Alex Soupir, Brandon Manley, Daniel Grass, Kosj Yamoah, Sumati Gupta, Laura Graham, Eric Singer, Jennifer King, …
The Journal of urology, Vol.215(5S), p.e1557
05/2026
DOI: 10.1097/01.JU.0001191752.72730.24.06

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Abstract

INTRODUCTION AND OBJECTIVES: Resistance to ADT in metastatic prostate cancer remains a major challenge. Next-generation agents like Abiraterone target the AR pathway more effectively, yet patient response is heterogeneous. Evidence suggests AR-V7 contributes to resistance by sustaining AR activity, yet there has been limited clinical translation. This study investigates novel AR splice variants (SVs) as potential predictive biomarkers of response to abiraterone and prednisone (AA/P) and prognostic of survival. METHODS: Samples from prospective trial, “PROstate cancer Medically Optimized genome enhanced ThErapy (PROMOTE) and retrospectively from Oncology Research Information Exchange Network (ORIEN). PROMOTE included chemotherapy-naïve mCRPC patients who progressed on ADT prior to AA/P treatment and had biopsies of metastasis before treatment. We evaluated unique splicing events in AR signaling. Multivariable Cox regression was performed, comparing individual splice junctions and available clinical factors with overall survival (OS), time to treatment change (TTTC), and progression. SVs identified in PROMOTE were validated in ORIEN prostate tissue samples. RESULTS: We developed a splicing composite signature, consisting of 5 novel AR SVs that were associated with AA/P response and OS. In PROMOTE, 72 patients were included. 23 (32%) patients harbored at least one novel AR SV. Median age was 72 and 60% had high-volume metastatic disease. Median PSA at enrollment was 11.9 ng/mL. Median follow-up was 28.8 months. AR splicing signature was independently associated with OS (HR 4.13, 95% CI 2.10 – 8.11), TTTC (HR 4.12, 95% CI 2.11 – 8.03), and 90-day progression (HR 3.45, 95%CI 1.08 – 11.80). Within ORIEN, 723 patients with primary samples were included. AR SV composite signature was associated with worse OS in ORIEN on KM analysis, p<0.0001 (Figure 1). CONCLUSIONS: We describe an AR splicing signature consisting of 5 novel AR SVs that is predictive of response to AA/P and prognostic for overall survival. Further investigation of these variants may lead to a better understanding of prostate cancer resistance to AA/P and may lead to clinically relevant biomarkers and therapies.

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