Yazgan Satı Coşkun, Kayaş Kamil, Arslan Çağatay, Kapar Caner, Öztekin Şura, Ceylan Furkan, Bölek Hatice, Elboğa Umut, Ateş Öztürk, Tural Deniz, Kuş Tülay, Şendur Mehmet Ali Nahit, Yekedüz Emre, Küçük Nuriye Özlem, Çıngı Özdemir Elif, Ürün Yüksel
Department of Medical Oncology, Ankara University School of Medicine, Ankara 06620, Turkey.
Ankara University Cancer Institute, Ankara, 06620, Turkey.
Oncologist. 2025 Sep 1;30(9). doi: 10.1093/oncolo/oyaf213.
Prostate-specific membrane antigen (PSMA) is a key target in metastatic castration resistance prostate cancer (mCRPC). Enzalutamide, an androgen receptor pathway inhibitor (ARPi), increases PSMA expression, potentially enhancing 177Lu-PSMA-617 radioligand therapy. This study evaluates the impact of prior ARPi (enzalutamide vs abiraterone acetate [AA]) on PSMA expression, PFS, and OS.
A retrospective analysis of 214 mCRPC patients treated with 177Lu-PSMA-617 across six Turkish centers (2015-2025) was conducted. Patients were grouped by prior ARPi therapy. PFS and OS were analyzed using Kaplan-Meier and Cox regression methods.
Among 103 patients receiving ARPi before 177Lu-PSMA-617, 59 (57%) had enzalutamide and 44 (43%) AA. Median PFS was 7.6 months for enzalutamide versus 5.3 months for AA (P = .068). Median OS was significantly longer with enzalutamide (12.8 vs 6.9 months, P = .021). Patients with Eastern Cooperative Oncology Group Performance Scores (ECOG PS) 0-1 had significantly longer OS (27.6 vs 6.9 months for PS 2-3, P < .0001). Higher PSMA SUVmax (>20) correlated with longer OS (15.1 vs 7.8 months, P = .016). Among 86 patients with detectable PSMA SUVmax, 53 had SUVmax > 20; 66% had prior enzalutamide and 34% AA. Median OS was four months longer with enzalutamide (18.1 vs 13.9 months P = .120). Multivariate analysis identified ARPi type (HR: 2.24, P = .033) and ECOG PS (HR: 5.22, P < .0001) as independent OS predictors.
Enzalutamide prior to 177Lu-PSMA-617 significantly improves OS and enhances PSMA expression compared to AA. These findings highlight the importance of treatment sequencing in mCRPC and warrant further prospective studies.
前列腺特异性膜抗原（PSMA）是转移性去势抵抗性前列腺癌（mCRPC）的关键靶点。恩杂鲁胺是一种雄激素受体通路抑制剂（ARPi），可增加PSMA表达，可能增强177Lu-PSMA-617放射性配体疗法。本研究评估既往ARPi（恩杂鲁胺与醋酸阿比特龙[AA]）对PSMA表达、无进展生存期（PFS）和总生存期（OS）的影响。
对土耳其六个中心（2015 - 2025年）接受177Lu-PSMA-617治疗的214例mCRPC患者进行回顾性分析。患者按既往ARPi治疗分组。采用Kaplan-Meier法和Cox回归方法分析PFS和OS。
在103例在接受177Lu-PSMA-617治疗前接受ARPi治疗的患者中，59例（57%）使用恩杂鲁胺，44例（43%）使用AA。恩杂鲁胺组的中位PFS为7.6个月，而AA组为5.3个月（P = 0.068）。恩杂鲁胺组的中位OS显著更长（12.8个月对6.9个月，P = 0.021）。东部肿瘤协作组体能状态评分（ECOG PS）为0 - 1的患者OS显著更长（PS 2 - 3组为6.9个月，P < 0.0001）。较高的PSMA最大标准化摄取值（SUVmax）（>20）与更长的OS相关（15.1个月对7.8个月，P = 0.016）。在86例可检测到PSMA SUVmax的患者中，53例SUVmax > 20；其中66%曾使用恩杂鲁胺，34%使用AA。恩杂鲁胺组的中位OS长4个月（18.1个月对13.9个月，P = 0.120）。多变量分析确定ARPi类型（风险比：2.24，P = 0.033）和ECOG PS（风险比：5.22，P < 0.0001）为独立的OS预测因素。
与AA相比，在使用177Lu-PSMA-617之前使用恩杂鲁胺可显著改善OS并增强PSMA表达。这些发现突出了mCRPC治疗顺序的重要性，值得进一步开展前瞻性研究。
