Androgen deprivation therapy intensification (ADTi) with androgen receptor pathway inhibitors (ARPI), docetaxel or both has been shown to improve survival outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Currently, baseline tumor genomic markers have no role in clinical decision-making in patients with mHSPC.
In this IRB-approved retrospective study, patients diagnosed with mHSPC who underwent comprehensive genomic profiling from primary tissue or metastatic sites and treated with ADTi were included. Genomic alterations with an incidence ≥5% were included in the analysis.
A total of 276 patients were eligible and included in the study. In the multivariable analysis, TP53 (HR 1.71, 95% CI 1.17-2.49, p = 0.006), RB1 (HR 2.32, 95% CI 1.28-4.18, p = 0.006), PTEN (HR 1.74, 95% CI 1.12-2.7, p = 0.014), and BRCA2 (HR 2.64, 95% CI 1.42-4.92, p = 0.003) were associated with significantly shorter PFS, while TP53 (HR 1.63, 95% CI 1.00-2.64, p = 0.049), RB1 (HR 4.5, 95% CI 2.32-8.70, p < 0.001), and PTEN (HR 2.4, 95% CI 1.38-4.2, p = 0.003) were associated with significantly worse OS.
This is one of the largest studies to show the association of baseline tumor genomic markers with survival in patients with mHSPC treated with ADTi. Upon external validation, these results may aid in developing a clinical-genomic risk stratification model, patient counseling, and prognostication.
Prostate cancer and prostatic diseases. 2025 Jan 31 [Epub ahead of print]
Georges Gebrael, Nicolas Sayegh, Chadi Hage Chehade, Yeonjung Jo, Arshit Narang, Beverly Chigarira, Nishita Tripathi, Ayana Srivastava, Clara Tandar, Jessica F Williams, Diya Garg, Richard Ji, Benjamin L Maughan, Umang Swami, Neeraj Agarwal
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Division of Biostatistics, Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT, USA., Department of Pathology, University of Utah, Salt Lake City, UT, USA., Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. ., Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. .