Genomic biomarkers of survival in patients with metastatic hormone-sensitive prostate cancer undergoing intensified androgen deprivation therapy.

IF 5.1 2区医学 Q1 ONCOLOGY

Prostate Cancer and Prostatic Diseases Pub Date : 2025-01-31 DOI:10.1038/s41391-025-00936-1

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

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引用次数: 0

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊

Prostate Cancer and Prostatic Diseases 医学-泌尿学与肾脏学

CiteScore

10.00

自引率

6.20%

发文量

142

审稿时长

6-12 weeks

期刊介绍： Prostate Cancer and Prostatic Diseases covers all aspects of prostatic diseases, in particular prostate cancer, the subject of intensive basic and clinical research world-wide. The journal also reports on exciting new developments being made in diagnosis, surgery, radiotherapy, drug discovery and medical management. Prostate Cancer and Prostatic Diseases is of interest to surgeons, oncologists and clinicians treating patients and to those involved in research into diseases of the prostate. The journal covers the three main areas - prostate cancer, male LUTS and prostatitis. Prostate Cancer and Prostatic Diseases publishes original research articles, reviews, topical comment and critical appraisals of scientific meetings and the latest books. The journal also contains a calendar of forthcoming scientific meetings. The Editors and a distinguished Editorial Board ensure that submitted articles receive fast and efficient attention and are refereed to the highest possible scientific standard. A fast track system is available for topical articles of particular significance.