Evidence map›Paper›PMID 40968764›Full record

SynthesisInternational journal of surgery (London, England)2026

Exploring the efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer with homologous recombination repair alteration: a meta-analysis based on subgroups and reconstructed individual patient data.

Fuxun Zhang, Zhirong Luo, Yang Xiong, Qi Xue, Xuyan Guo, Qiang Fu, Yong Jiao, Wei Zhang, Pati-Alam Alisha, Uzoamaka Adaobi Okoli and 1 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in International journal of surgery (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Fuxun ZhangDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.ORCID 0000-0003-0113-0395
Zhirong LuoDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yang XiongDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Qi XueDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xuyan GuoDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Qiang FuDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yong JiaoDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Wei ZhangDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Pati-Alam AlishaDivision of Surgery & Interventional Science, University College London, London, UK.
Uzoamaka Adaobi OkoliDivision of Surgery & Interventional Science, University College London, London, UK.
Geng ZhangDepartment of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.ORCID 0009-0007-0376-3096

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTreatment for metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) alteration remains a challenge. Recently published trials have evaluated the poly (ADP-ribose) polymerase inhibitors (PARPIs) in mCRPC. However, the efficacy in subgroup with specific HRR gene mutation and treatment protocol requires further elucidation. This meta-analysis aims to explore the efficacy of PARPIs based on subgroups and reconstructed individual patient data (IPD).

methodsLiterature was searched using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to April 2025. The primary outcome was radiographic progression-free survival (rPFS), and the secondary outcomes included overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and adverse events (AEs). Hazard ratios (HRs) and risk ratios (RRs) were pooled as the indicators using inverse-variance and Mantel-Haenszel methods. IPD was reconstructed from Kaplan-Meier curve. Survival analysis was performed using Cox proportional hazards model based on the reconstructed IPD. Heterogeneity was assessed by I 2 and sensitivity analysis. Publication bias was examined via contour‑enhanced funnel plots.

resultsData of 1840 mCRPC patients with HRR alteration from five pivotal phase III clinical trials were analyzed. PARPIs significantly improved overall rPFS (HR: 0.55) and OS (HR: 0.85). PARPIs also prolonged rPFS across the subgroups defined by clinicopathologic features. In BRCA1/2 subgroup, survival benefits were prominent for rPFS (HR 0.32) and OS (HR 0.70). For patients with non- BRCA alterations, no benefits of PARPIs were detected for rPFS and OS in ATM subgroup, and for OS in CDK12 subgroup. Survival analyses indicated that PARPIs treatment was significantly associated with the improved rPFS (HR: 0.73, P < 0.001) and PSA-PFS (HR: 0.80, P = 0.020) in the overall population, and revealed OS benefit in BRCA1/2 subgroup (HR: 0.77, P = 0.030). Comparing with monotherapy, combination regimen of PARPIs provided greater benefits for rPFS (HR: 0.56, P < 0.001)and OS (HR: 0.64., P < 0.001).

conclusionsPARPIsimprove survival in mCRPC patients with BRCA1/2 mutation, but have no effect in those with ATM mutation. Comparing with PARPIs monotherapy, the combination regimen provides greater survival benefit in the overall population. Future investigation should validate these findings in real-world settings.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsProstatic Neoplasms, Castration-ResistantRecombinational DNA RepairHumansMalePoly(ADP-ribose) Polymerase Inhibitorsindividual patient datapoly (ADP-ribose) polymerase inhibitorprostate cancersurvivaltreatment

Identifiers

PMID40968764
PMCPMC12825753

What Socratic holds

Textmetadata
LicenceCC BY-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.