Evidence map›Paper›PMID 41643695›Full record

SynthesisThe Lancet. Oncology2026

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.

Chad Tang, Alex D Sherry, Hyunsoo Hwang, David P Farris, Giulio Francolini, Vanessa Di Cataldo, Lorenzo Livi, Phuoc Tran, Paul G Corn, Ana Aparicio and 18 more

Erratum issued Registry-linked trialAbstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07782112 (PEACE-9 - ESCALATE-RT), which is not on this map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–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.

NCT07782112 phase3not yet recruitingnot on this map

PEACE-9 - ESCALATE-RT: A Phase III Randomized Study in Patients With High-risk PSA Relapse After Local Therapy Treated With Enzalutamide Plus Androgen Deprivation Therapy and Comparing MDT ± Pelvic Radiotherapy Versus no Further Treatment

TypeinterventionalSponsorEnte Ospedaliero Cantonale, BellinzonaRan2026 to 2030Enrolled140ConditionsProstatic Neoplasms, Biochemical Recurrence, Oligometastatic Prostate CancerArmsRadiotherapy for MDT ± WPRT, Androgen Deprivation Therapy (ADT), Enzalutamide
3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Trends in radiation oncology between 2015 and 2022: report from a German university radio-oncology department.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Article
  6. Clinical outcomes of stereotactic body radiotherapy in oligometastatic disease: a national real-world cohort study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  7. Individualized radiotherapy of bone metastases from prostate cancer: time trends and 5-year survival results.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Article
  8. Article
  9. Review
  10. [WOLVERINE, a meta-analysis on stereotactic radiotherapy of oligometastases in prostate cancer].Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Article
  11. Oligometastatic Prostate Cancer: Clues from an N-of-1.Journal of clinical medicine · 2026
    Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Chad TangDepartment of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ctang1@mdanderson.org.
Alex D SherryDepartment of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Hyunsoo HwangDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David P FarrisResearch Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Giulio FrancoliniRadiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence University, Firenze, Italy.
Vanessa Di CataldoRadiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence University, Firenze, Italy.
Lorenzo LiviRadiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence University, Firenze, Italy.
Phuoc TranDepartment of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paul G CornDepartment of Genitourinary Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ana AparicioDepartment of Genitourinary Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gabriele SimontacchiRadiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence University, Firenze, Italy.
Ana P KiessDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jarey H WangDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Valerie FonteyneDepartment of Human Structure and Repair, Ghent University, Belgium.
Renee BultijnckDepartment of Human Structure and Repair, Ghent University, Belgium.
Ryan PhillipsDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Matthew P DeekDepartment of Radiation Oncology, Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Robert OlsonDivision of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada.
Stephen HarrowDepartment of Clinical Oncology, Beatson West of Scotland Cancer Center, Glasgow, UK.
Giulia MarvasoDepartment of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Department of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
Chiara LorubbioDepartment of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
Barbara A Jereczek-FossaDepartment of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Department of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
Ethan B LudmirDepartment of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pierre BlanchardDepartment of Radiation Oncology, Gustave Roussy Cancer Campus, INSERM 1018 CESP, University Paris-Saclay, Villejuif, France.
Andrew WarnerDivision of Radiation Oncology, Department of Oncology, Western University and London Health Sciences Centre, London, ON, Canada.
Ryan SunDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David A PalmaDivision of Radiation Oncology, Department of Oncology, Western University and London Health Sciences Centre, London, ON, Canada.
Piet OstDepartment of Human Structure and Repair, Ghent University, Belgium; Department of Radiation Oncology, Iridium Network, Wilrijk, Belgium.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Resource Sharing CoreU54CA273956 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Amit Sawant, Nicole L Simone · 2022 to 2026
$8.9M
NCI NIH HHS P30 CA016672NCI NIH HHS U54 CA273956
6 · The paper itself

Abstract

backgroundOligometastatic disease represents the proximal end of a metastatic spectrum. Metastasis-directed therapy (MDT) is increasingly used to treat oligometastatic disease despite the absence of level 1 evidence. We amalgamated individual patient data across trials to evaluate the effectiveness of MDT for oligometastatic prostate cancer.

methodsWe conducted a systematic review and individual patient data meta-analysis. We systematically searched Embase, PubMed, CENTRAL, MEDLINE, and ClinicalTrials.gov to identify randomised trials of MDT enrolling patients with oligometastatic prostate cancer. 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 survival and overall survival. This systematic review was conducted from database creation to Nov 3, 2023, and was updated on May 4, 2025. Data appraisal was conducted using Covidence with two investigators (CT and ADS) performing independent screens. Studies were evaluated using the Cochrane Collaboration's risk-of-bias assessment (version 2.0). Individual patient data were provided by investigators. Coprimary endpoints were progression-free survival and overall survival. Secondary endpoints were radiographic progression-free survival and 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. The primary analysis included a trial-level analysis using a random effects model and a patient-level analysis stratifying by trial. This meta-analysis is registered with PROSPERO (CRD42023479078).

findingsOf 2975 studies identified for screening, seven phase 2 studies randomly assigning 574 men were included. 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). 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). The association between MDT and overall survival showed 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.

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

fundingPhilanthropic gift and National Cancer Institute.

Indexed as

Prostatic NeoplasmsStandard of CareHumansMaleNeoplasm MetastasisProgression-Free SurvivalRandomized Controlled Trials as Topic

Identifiers

PMID41643695
PMCPMC13286301

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Registered trials

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 OpenQuestion graph.