Metastasis-directed therapy and standard of care versus standard of care for oligometastatic prostate cancer (WOLVERINE): a systematic review and individual patient data meta-analysis from the X-MET collaboration.

Metastasis-directed therapy (MDT) is increasingly used to treat oligometastatic disease despite the absence of level 1 evidence.

尽管缺乏一级证据，但转移性导向治疗（MDT）越来越多地被用于治疗寡转移性疾病。

We amalgamated individual patient data across trials to evaluate the effectiveness of MDT for oligometastatic prostate cancer.

我们整合了各试验中的个别患者数据，以评估多学科团队（MDT）对寡转移性前列腺癌的疗效。

Methods

We conducted a systematic reviewand individual patient data meta-analysis.

我们进行了系统综述和个别患者数据的荟萃分析。

We systematically searched Embase, PubMed, CENTRAL, MEDLINE, and ClinicalTrials.gov to identify randomised trials of MDT enrolling patients with oligometastatic prostate cancer.

我们系统地搜索了Embase、PubMed、CENTRAL、MEDLINE和ClinicalTrials.gov，以确定纳入寡转移性前列腺癌患者的多学科团队(MDT)的随机试验。

Inclusion criteria were published randomised prospective trials enrolling patients with oligometastatic (up to five metastases) prostate cancer, in which investigators recorded sufficient data to evaluate progression-free survivaland overall survival. This systematic reviewwas conducted from database creation to Nov 3, 2023, and was updated on May 4, 2025.

纳入标准是已发表的随机前瞻性试验，这些试验招募了寡转移性（最多五处转移）前列腺癌患者，在这些试验中，研究人员记录了足够的数据以评估无进展生存期和总生存期。这项系统评价从数据库创建到2023年11月3日进行，并在2025年5月4日进行了更新。

Data appraisal was conducted using Covidence with two investigators (CT and ADS) performing independent screens.

数据评估使用Covidence进行，由两名研究员（CT和ADS）执行独立筛选。

Studies were evaluated using the Cochrane Collaboration's risk-of-bias assessment (version 2.0).

研究使用Cochrane协作组织的风险偏倚评估（版本2.0）进行评估。

Individual patient data were provided by investigators.

研究者提供了个体患者数据。

Coprimary endpoints were progression-free survivaland overall survival. Secondary endpoints were radiographic progression-free survivaland castration resistance-free survival. The primary analysis was conducted in the subset of studies in which patients were randomly assigned to MDT plus standard of care (SOC) versus SOC.

主要终点是无进展生存和总生存。次要终点是影像学无进展生存和去势抵抗无进展生存。主要分析是在患者被随机分配到多学科团队加标准治疗（SOC）与仅接受SOC的研究子集中进行的。

The primary analysis included a trial-level analysis using a random effects model and a patient-level analysis stratifying by trial. This meta-analysisis registered with PROSPERO (CRD42023479078).

主要分析包括使用随机效应模型的试验级分析和按试验分层的患者级分析。这项荟萃分析已在PROSPERO注册（CRD42023479078）。

Results

Of 2975 studies identified for screening, seven phase 2 studies randomly assigning 574 men were included.

在筛选出的2975项研究中，包括了7项随机分配574名男性的2期研究。

Six trials randomly assigning 472 patients to MDT plus SOC (n=248) versus SOC (n=224) were used to evaluate MDT and had a median follow-up time of 40·7 months (IQR 25·6-53·7).

使用了六项随机试验，共472名患者，其中248名接受MDT加SOC治疗，224名仅接受SOC治疗，以评估MDT的效果，中位随访时间为40.7个月（四分位数间距25.6-53.7）。

MDT was associated with improved progression-free survival(trial-level hazard ratio[HR] 0·44, [95% CI 0·35-0·56], p<0·0001; patient-level HR 0·45 [0·35-0·57], p<0·0001), radiographic progression-free survival(trial-level HR 0·60 [0·42-0·85], p=0·0039; patient-level HR 0·59 [0·46-0·76], p<0·0001), and castration resistance-free survival (trial-level HR 0·58 [95% CI 0·37-0·92], p=0·019; patient-level HR 0·58 [95% CI 0·37-0·91], p=0·017).

MDT与改善无进展生存期（试验水平风险比[HR] 0.44，[95% CI 0.35-0.56]，p<0.0001；患者水平HR 0.45 [0.35-0.57]，p<0.0001）、影像学无进展生存期（试验水平HR 0.60 [0.42-0.85]，p=0.0039；患者水平HR 0.59 [0.46-0.76]，p<0.0001）和去势抵抗无进展生存期（试验水平HR 0.58 [95% CI 0.37-0.92]，p=0.019；患者水平HR 0.58 [95% CI 0.37-0.91]，p=0.017）相关。

The association between MDT and overall survivalshowed an HR of 0·63 (95% CI 0·39-1·00, p=0·051) in trial-level analyses and 0·64 (95% CI 0·40-1·01, p=0·057) in patient-level analyses.

MDT与总生存之间的关联在试验级分析中显示出风险比为0.63（95%置信区间0.39-1.00，p=0.051），在患者级分析中为0.64（95%置信区间0.40-1.01，p=0.057）。

interpretation

WOLVERINE showed a benefit with MDT for oligometastatic prostate cancer in progression-free survival, radiological progression-free survival, and castration resistance-free survival. Overall survivalbenefit was not significant and further research is needed.

WOLVERINE研究显示，对于寡转移性前列腺癌，MDT在无进展生存、影像学无进展生存和去势抵抗无进展生存方面显示出益处。总生存的益处不显著，需要进一步研究。

funding

Philanthropic gift and National Cancer Institute.

慈善捐赠与国家癌症研究所。