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. 2025 Sep 1;30(9):oyaf213.
doi: 10.1093/oncolo/oyaf213.

Enhancing outcomes in mCRPC: the impact of androgen receptor inhibitor sequencing before 177Lu-PSMA-617 therapy

Satı Coşkun Yazgan  1   2 , Kamil Kayaş  3 , Çağatay Arslan  4 , Caner Kapar  5 , Şura Öztekin  6 , Furkan Ceylan  7 , Hatice Bölek  1   2 , Umut Elboğa  8 , Öztürk Ateş  6 , Deniz Tural  5 , Tülay Kuş  3 , Mehmet Ali Nahit Şendur  7 , Emre Yekedüz  1   2   9 , Nuriye Özlem Küçük  10 , Elif Çıngı Özdemir  11 , Yüksel Ürün  1   2
Affiliations

Enhancing outcomes in mCRPC: the impact of androgen receptor inhibitor sequencing before 177Lu-PSMA-617 therapy

Satı Coşkun Yazgan et al. Oncologist. .

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: 177Lu-PSMA-617; ARPi; Abiraterone acetate; Enzalutamide; PSMA.

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Conflict of interest statement

Yüksel Ürün declared research funding (Institutional and personal) from Turkish Oncology Group. Yüksel Ürün has served on the advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Eczacıbası, Gilead, Janssen, Merck, Novartis, Pfizer, Roche. Yüksel Ürün received honoraria or has served as a consultant for Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Eczacıbasi, Janssen, Merck, Novartis, Pfizer, Roche. All remaining authors have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Kaplan-Meier survival analysis according to ARPi groups.
See this image and copyright information in PMC

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