Prognostic factors of PSMA-targeted radioligand therapy in metastatic castration-resistant prostate cancer: a systematic review and meta-analysis
Takafumi Yanagisawa, Akihiro Matsukawa, Paweł Rajwa, Marcin Miszczyk, Tamás Fazekas, Benjamin Pradère, Keiichiro Miyajima, Yuki Enei, Angelo Cormio, Alessandro Dematteis, Timo Soeterik, Atsuya Okada, Hidetoshi Kuruma, Nat Lenzo, Shahrokh F. Shariat, Kenta Miki, Takahiro Kimura
Abstract
Abstract Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a widely accepted treatment option for metastatic castration-resistant prostate cancer (mCRPC). However, synthesized evidence regarding potential prognostic factors for oncologic outcomes in patients treated with PSMA-RLT is lacking. We aimed to synthesize prognosticators of oncologic outcomes in patients with mCRPC treated with PSMA-RLT. Methods PubMed®, Web of Science™, and Embase® databases were systemically searched in March 2025 for studies. Eligible studies investigated pretreatment clinical, hematologic, or radiographical prognostic factors for oncologic outcomes, such as progression-free (PFS) or overall survivals (OS) in patients with mCRPC treated with PSMA-RLT. Only parameters assessed through multivariable analysis adjusting for potential confounders were synthesized. ( CRD42024598718 ) Results A total of 39 studies ( n = 4819) were included in the systematic review and 32 studies ( n = 3038) were included in the meta-analysis. Prior chemotherapy (pooled HR: 1.43, 95%CI: 1.10–1.85), visceral metastases (pooled HR: 1.41, 95%CI: 1.05–1.89), and liver metastasis (pooled HR: 1.75, 95%CI: 1.37–2.25) were associated with worse PFS. Poor performance status (PS) (pooled HR: 1.99, 95%CI: 1.45–2.74), prior chemotherapy (pooled HR: 1.39, 95%CI: 1.19–1.63), visceral metastasis (pooled HR: 1.65, 95%CI: 1.33–2.05), bone metastasis (pooled HR: 2.09, 95%CI: 1.39–3.13), liver metastasis (pooled HR: 2.15, 95%CI: 1.84–2.50), and lower pretreatment hemoglobin levels (pooled HR: 1.25, 95%CI: 1.09–1.43) were associated with poorer OS. Higher pretreatment SUV mean was associated with improved OS benefit (pooled HR: 0.91, 95%CI: 0.85–0.97). PSA decline after treatment initiation, particularly ≥50%, was associated with improved PFS and OS. Conclusions Prior chemotherapy use and location of metastases influence the prognosis of patients with mCRPC treated with PSMA-RLT. A higher pre-treatment SUV mean is predictive of better PSMA-RLT efficacy, and a greater PSA 'response is associated with improved survival outcomes. These findings may help guide clinical decision-making regarding PSMA-RLT and support prognostication of its oncological benefits.