Gebrael Georges, Sayegh Nicolas, Hage Chehade Chadi, Jo Yeonjung, Narang Arshit, Chigarira Beverly, Tripathi Nishita, Srivastava Ayana, Tandar Clara, Williams Jessica F, Garg Diya, Ji Richard, Maughan Benjamin L, Swami Umang, Agarwal Neeraj
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Prostate Cancer Prostatic Dis. 2025 Jan 31. doi: 10.1038/s41391-025-00936-1.
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.
雄激素剥夺治疗强化（ADTi）联合雄激素受体通路抑制剂（ARPI）、多西他赛或两者同时使用，已被证明可改善转移性激素敏感性前列腺癌（mHSPC）患者的生存结局。目前，基线肿瘤基因组标志物在mHSPC患者的临床决策中并无作用。
在这项经机构审查委员会批准的回顾性研究中，纳入了被诊断为mHSPC且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ADTi治疗的患者。分析纳入了发生率≥5%的基因组改变。
共有276例患者符合条件并纳入研究。在多变量分析中，TP53（风险比[HR] 1.71，95%置信区间[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）与显著更短的无进展生存期（PFS）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 < 0.001）和PTEN（HR 2.4，95% CI 1.38 - 4.2，p = 0.003）与显著更差的总生存期（OS）相关。
这是最大规模的研究之一，显示了基线肿瘤基因组标志物与接受ADTi治疗的mHSPC患者生存之间的关联。经外部验证后，这些结果可能有助于建立临床 - 基因组风险分层模型、患者咨询和预后评估。
