The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies

Marcin Miszczyk, Pawel Rajwa, Takafumi Yanagisawa, Zuzanna Nowicka, Sung Ryul Shim, Ekaterina Laukhtina, Tatsushi Kawada, Markus von Deimling, Benjamin Pradere, Juan Gómez Rivas, Giorgio Gandaglia, Roderick C N van den Bergh, Gregor Goldner, Stephane Supiot, Thomas Zilli, Quoc-Dien Trinh, Paul L Nguyen, Alberto Briganti, Piet Ost, Guillaume PloussardShahrokh F Shariat*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

16 Citations (Scopus)
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Abstract

CONTEXT: 

Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.

OBJECTIVE: 

To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.

EVIDENCE ACQUISITION: 

We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.

EVIDENCE SYNTHESIS: 

We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.

CONCLUSIONS: 

MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.

PATIENT SUMMARY: 

Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.

Original languageEnglish
Pages (from-to)125-138
Number of pages14
JournalEuropean Urology
Volume85
Issue number2
DOIs
Publication statusPublished - Feb 2024

Bibliographical note

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

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