Department of Medical Oncology, Campus Bio-Medico University, via Alvaro del Portillo, 200, 00128, Rome, Italy.
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Maroncelli, 40, 47014, Meldola, Italy.
Sci Rep. 2022 May 5;12(1):7319. doi: 10.1038/s41598-022-10751-6.
In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel represent the referring options. There is no evidence that the GS/GG systems can add information to guide the choice between AR-directed drugs and docetaxel in the first-line setting of mCRPC. Nowadays there are no validated biomarkers, which define patients who may benefit or not from hormonal treatments or chemotherapy. Androgen receptor (AR) copy number variations (CNV) are predictive factors of poor response to abiraterone and enzalutamide. There are no available data about the association between AR CNV and GG. In this retrospective study, we analysed the association of the highest GG score with AR CNV and their impact on the clinical outcome of AR-directed drugs and docetaxel as first-line therapy for mCRPC patients. Patients benefit from docetaxel, abiraterone or enzalutamide regardless the GG. However, the presence of GG5 and AR CNV gain identifies a subgroup of patients with poor prognosis, which could benefit from front-line docetaxel instead of AR-directed drugs.
在局限性前列腺癌（PCa）中，分级分组（GG）和 Gleason 评分（GS）具有明确的预后作用。在转移性去势抵抗性前列腺癌（mCRPC）中，GS 和 GG 的预后作用定义不明确。在 mCRPC 的一线治疗中，雄激素受体（AR）靶向药物（醋酸阿比特龙、恩扎鲁胺）和多西他赛是参考选择。目前尚无证据表明 GS/GG 系统可以提供信息，以指导在 mCRPC 的一线治疗中选择 AR 靶向药物和多西他赛。目前尚无经过验证的生物标志物可以确定哪些患者可能从激素治疗或化疗中获益或不受益。雄激素受体（AR）拷贝数变异（CNV）是对阿比特龙和恩扎鲁胺反应不良的预测因素。目前尚无关于 AR CNV 与 GG 之间关联的可用数据。在这项回顾性研究中，我们分析了最高 GG 评分与 AR CNV 的关联，以及它们对 AR 靶向药物和多西他赛作为 mCRPC 患者一线治疗的临床结局的影响。无论 GG 如何，患者都能从多西他赛、阿比特龙或恩扎鲁胺中获益。然而，存在 GG5 和 AR CNV 增益的患者预后较差，可能受益于一线多西他赛而不是 AR 靶向药物。
