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Background <p>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.</p> Methods <p>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. (<b>CRD42024598718</b>)</p> Results <p>A total of 39 studies (<i>n</i> = 4819) were included in the systematic review and 32 studies (<i>n</i> = 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<sub>mean</sub> 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.</p> Conclusions <p>Prior chemotherapy use and location of metastases influence the prognosis of patients with mCRPC treated with PSMA-RLT. A higher pre-treatment SUV<sub>mean</sub> 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.</p>

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Prognostic factors of PSMA-targeted radioligand therapy in metastatic castration-resistant prostate cancer: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月8日

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  • Takafumi Yanagisawa,
  • Akihiro Matsukawa,
  • Paweł Rajwa,
  • Marcin Miszczyk,
  • Tamás Fazekas,
  • Benjamin Pradere,
  • Keiichiro Miyajima,
  • Yuki Enei,
  • Angelo Cormio,
  • Alessandro Dematteis,
  • Timo Soeterik,
  • Atsuya Okada,
  • Hidetoshi Kuruma,
  • Nat Lenzo,
  • Shahrokh F. Shariat,
  • Kenta Miki,
  • Takahiro Kimura

摘要

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 SUVmean 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 SUVmean 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.