接受强化雄激素剥夺治疗的转移性激素敏感前列腺癌患者生存的基因组生物标志物

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

摘要

雄激素剥夺强化治疗（ADTi）与雄激素受体途径抑制剂（ARPI）、多西紫杉醇或两者兼用已被证明可改善转移性激素敏感前列腺癌（mHSPC）患者的生存结果。目前，基线肿瘤基因组标记在mHSPC患者的临床决策中没有作用。方法：在这项经irb批准的回顾性研究中，被诊断为mHSPC的患者接受了来自原发组织或转移部位的全面基因组分析，并接受了ADTi治疗。发生率≥5%的基因组改变被纳入分析。结果：共有276例患者符合条件并纳入研究。在多变量分析中，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）和BRCA2 （HR 2.64, 95% CI 1.42-4.92, p = 0.003）与PFS显著缩短相关，而TP53 （HR 1.63, 95% CI 1.00-2.64, p = 0.049）、RB1 （HR 4.5, 95% CI 2.32-8.70, p = 0.049）与PFS显著缩短相关。这是显示经ADTi治疗的mHSPC患者的基线肿瘤基因组标记物与生存相关的最大研究之一。在外部验证后，这些结果可能有助于开发临床-基因组风险分层模型，患者咨询和预后。

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

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.