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

Takafumi Yanagisawa^#^{1

2

3}, Akihiro Matsukawa^#^{1

2}, Paweł Rajwa^{1

4}, Marcin Miszczyk^{1

5}, Tamás Fazekas^{1

6}, Benjamin Pradere^{1

7}, Keiichiro Miyajima^{1

2}, Yuki Enei^{2

3}, Angelo Cormio^{1

8}, Alessandro Dematteis^{1

9}, Timo Soeterik¹⁰, Atsuya Okada^{3

11}, Hidetoshi Kuruma^{3

12}, Nat Lenzo¹³, Shahrokh F Shariat^{14

15

16

17

18

19

20

21

22}, Kenta Miki^{2

3

12}, Takahiro Kimura²³

Affiliations

¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
² Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
³ Theranostics Yokohama, Yokohama, Japan.
⁴ Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland.
⁵ Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland.
⁶ Department of Urology, Semmelweis University, Budapest, Hungary.
⁷ Department of Urology, La Croix Du Sud Hospital, Quint Fonsegrives, France.
⁸ Department of Urology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Ancona, Università Politecnica Delle Marche, Ancona, Italy.
⁹ Department of Surgical Sciences, Division of Urology, AOU Città della Salute e della Scienza at Molinette Hospital and University of Turin, Turin, Italy.
¹⁰ Department of Radiation Oncology, University Medical Center, Utrecht, Netherlands.
¹¹ Jinsenkai MI Clinic, Osaka, Japan.
¹² Bashamichi Sakura Clinic, Yokohama, Japan.
¹³ ICON Cancer Centre Theranostics, Perth, WA, Australia.
¹⁴ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
¹⁵ Department of Urology, Semmelweis University, Budapest, Hungary. shahrokh.shariat@meduniwien.ac.at.
¹⁶ Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. shahrokh.shariat@meduniwien.ac.at.
¹⁷ Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan. shahrokh.shariat@meduniwien.ac.at.
¹⁸ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. shahrokh.shariat@meduniwien.ac.at.
¹⁹ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. shahrokh.shariat@meduniwien.ac.at.
²⁰ Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduniwien.ac.at.
²¹ Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
²² Research Center for Evidence Medicine, Urology Department Tabriz University of Medical Sciences, Tabriz, Iran. shahrokh.shariat@meduniwien.ac.at.
²³ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. tkimura0809@gmail.com.

^# Contributed equally.

PMID: 41062813
DOI: 10.1038/s41391-025-01034-y

Review

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

Takafumi Yanagisawa et al. Prostate Cancer Prostatic Dis. 2025.

. 2025 Oct 8.

doi: 10.1038/s41391-025-01034-y. Online ahead of print.

Authors

Affiliations

¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
² Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
³ Theranostics Yokohama, Yokohama, Japan.
⁴ Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland.
⁵ Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland.
⁶ Department of Urology, Semmelweis University, Budapest, Hungary.
⁷ Department of Urology, La Croix Du Sud Hospital, Quint Fonsegrives, France.
⁸ Department of Urology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Ancona, Università Politecnica Delle Marche, Ancona, Italy.
⁹ Department of Surgical Sciences, Division of Urology, AOU Città della Salute e della Scienza at Molinette Hospital and University of Turin, Turin, Italy.
¹⁰ Department of Radiation Oncology, University Medical Center, Utrecht, Netherlands.
¹¹ Jinsenkai MI Clinic, Osaka, Japan.
¹² Bashamichi Sakura Clinic, Yokohama, Japan.
¹³ ICON Cancer Centre Theranostics, Perth, WA, Australia.
¹⁴ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
¹⁵ Department of Urology, Semmelweis University, Budapest, Hungary. shahrokh.shariat@meduniwien.ac.at.
¹⁶ Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. shahrokh.shariat@meduniwien.ac.at.
¹⁷ Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan. shahrokh.shariat@meduniwien.ac.at.
¹⁸ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. shahrokh.shariat@meduniwien.ac.at.
¹⁹ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. shahrokh.shariat@meduniwien.ac.at.
²⁰ Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduniwien.ac.at.
²¹ Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at.
²² Research Center for Evidence Medicine, Urology Department Tabriz University of Medical Sciences, Tabriz, Iran. shahrokh.shariat@meduniwien.ac.at.
²³ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. tkimura0809@gmail.com.

^# Contributed equally.

PMID: 41062813
DOI: 10.1038/s41391-025-01034-y

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.

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Conflict of interest statement

Competing interests: Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen and Sanofi. Shahrokh F. Shariat received follows: Honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda, Consulting or Advisory Role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda, Speakers Bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda, The other authors declare no conflicts of interest associated with this manuscript.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous