Evidence map›Paper›PMID 42360803›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2026

AI-Based Pathology Classifier Predicts Sensitivity to Enzalutamide in Metastatic Hormone-Sensitive Prostate Cancer: A Biomarker Analysis of the ENZAMET Trial.

Sebastian Medina, Naoto Tokuyama, Vaishnavi Putcha, Tilak Pathak, Pingfu Fu, Hayley Thomas, Vinod V Subhash, Sonia Yip, Hui-Ming Lin, Lisa G Horvath and 9 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02446405 (Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT02446405 phase3active not recruitingnot on this map

Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET

TypeinterventionalSponsorUniversity of SydneyRan2014 to 2027Enrolled1,125ConditionsProstatic NeoplasmsArmsEnzalutamide, NSAA, LHRHA or Surgical Castration
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
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

19 authors.

Sebastian MedinaThe Wallace H. Coulter Department of Biomedical Engineering , Georgia Tech and Emory University, Atlanta, Georgia.ORCID 0000-0002-4154-0519
Naoto TokuyamaThe Wallace H. Coulter Department of Biomedical Engineering , Georgia Tech and Emory University, Atlanta, Georgia.ORCID 0000-0002-7784-4901
Vaishnavi PutchaThe Wallace H. Coulter Department of Biomedical Engineering , Georgia Tech and Emory University, Atlanta, Georgia.ORCID 0009-0008-0970-4457
Tilak PathakThe Wallace H. Coulter Department of Biomedical Engineering , Georgia Tech and Emory University, Atlanta, Georgia.ORCID 0000-0002-9738-4172
Pingfu FuDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio.ORCID 0000-0002-2334-5218
Hayley ThomasNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia.ORCID 0009-0009-1285-1420
Vinod V SubhashAustralian and New Zealand Urogenital and Prostate Cancer Trials Group , Sydney, Australia.ORCID 0000-0001-6050-9915
Sonia YipNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia.ORCID 0009-0001-2574-487X
Hui-Ming LinAdvanced Prostate Cancer Group, Garvan Institute of Medical Research, Darlinghurst, Australia.ORCID 0000-0003-4892-6008
Lisa G HorvathDepartment of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia.ORCID 0000-0001-6842-9223
James G KenchDepartment of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, Australia.ORCID 0000-0001-8687-4988
Alison ZhangNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia.ORCID 0000-0002-1902-6863
Martin R StocklerNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia.ORCID 0000-0003-3793-8724
Anthony M JoshuaDepartment of Medical Oncology, The Kinghorn Cancer Centre, Sydney, Australia.ORCID 0000-0001-5159-4580
Arun AzadDepartment of Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.ORCID 0000-0001-7350-5622
Samantha R OakesAustralian and New Zealand Urogenital and Prostate Cancer Trials Group , Sydney, Australia.ORCID 0000-0003-1838-2310
Ian D DavisAustralian and New Zealand Urogenital and Prostate Cancer Trials Group , Sydney, Australia.ORCID 0000-0002-9066-8244
Christopher J SweeneySouth Australian Immunogenomics Cancer Institute, Adelaide University, Adelaide, Australia.ORCID 0000-0002-0398-6018
Anant MadabhushiThe Wallace H. Coulter Department of Biomedical Engineering , Georgia Tech and Emory University, Atlanta, Georgia.ORCID 0000-0002-5741-0399

Funding

Advanced Research Projects Agency for Health (ARPA-H) D25CA00140-00Astellas Pharma (Astellas)AstraZeneca United States (AZ)Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)BLRD VA IK6 BX006185Breast Cancer Research Foundation (BCRF)Bristol-Myers Squibb (BMS)Fund for Innovation in Cancer Informatics (ICI)National Cancer Institute (NCI) R01CA249992-01A1National Cancer Institute (NCI) R01CA257612-01A1National Cancer Institute (NCI) R01CA264017-01National Cancer Institute (NCI) R01CA268207-01National Cancer Institute (NCI) R01CA268287-01A1National Cancer Institute (NCI) U01CA113913-16A1National Cancer Institute (NCI) U01CA269181-01National Cancer Institute (NCI) U24CA274494-01National Cancer Institute (NCI) U54CA302465-01National Health and Medical Research Council (NHMRC) 1196225National Health and Medical Research Council (NHMRC) 2016274National Heart, Lung, and Blood Institute (NHLBI) R01HL151277-01A1National Heart, Lung, and Blood Institute (NHLBI) R01HL158071-01A1National Institute of Allergy and Infectious Diseases (NIAID) R01AI175555-01A1National Institute of Biomedical Imaging and Bioengineering (NIBIB) 75N92022D00015National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK118431National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK133090-01 (KMAP)National Institute on Aging (NIA) R01AG089759NIH Office of the Director (OD) 1OT2OD038065-01Prevent Cancer Foundation (PCF)Scott R. MacKenzie Foundation (Scott R. Mackenzie Foundation, Inc.)U.S. Department of Veterans Affairs (VA) I01CX002622U.S. Department of Veterans Affairs (VA) I01CX002776U.S. Department of Veterans Affairs (VA) IBX004121U.S. Department of Veterans Affairs (VA) IK6BX006185U.S. Department of Veterans Affairs (VA) LPOP-L0021U.S. National Library of Medicine (NLM) R01LM013864-01A1
6 · The paper itself

Abstract

purposeThe ENZAMET trial established that enzalutamide added to androgen deprivation therapy (ADT) improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC), but treatment response is heterogeneous. We tested whether the artificial intelligence pathology image classifier (APIC), previously developed and locked in CHAARTED, predicts OS benefit from enzalutamide in ENZAMET. EXPERIMENTAL

designThis biomarker study applied APIC to digitized hematoxylin and eosin specimens from ENZAMET [Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) 1304, NCT02446405]. ENZAMET randomized participants with mHSPC to ADT plus enzalutamide or nonsteroidal antiandrogen (NSAA), with early concurrent docetaxel permitted. APIC was applied without modification or retraining. The prespecified primary analysis evaluated the treatment-by-APIC interaction for OS using Cox models adjusted for standard clinical factors. Prespecified sensitivity analysis excluded participants receiving early concurrent docetaxel.

resultsAmong 1,125 participants, 492 with digitized tissue (median follow-up, 68.8 months) were eligible. APIC classified 316 (64%) as APIC negative and 176 (36%) as APIC positive. APIC significantly modified enzalutamide benefit (interaction P = 0.014). APIC-negative disease showed improved survival with enzalutamide versus NSAA [HR, 0.50; 95% confidence interval (CI), 0.35-0.73; 60-month OS, 76.5% vs. 58.3%], whereas APIC-positive disease showed limited evidence of benefit (HR, 1.04; 95% CI, 0.67-1.62; 60-month OS, 55.6% vs. 58.8%). In low-volume disease, enzalutamide improved survival in APIC-negative (HR, 0.31; 95% CI, 0.16-0.62) but not APIC-positive disease (HR, 1.04; 95% CI, 0.53-2.06; interaction P = 0.015). For non-docetaxel-treated participants, enzalutamide benefit was greater in APIC-negative (HR, 0.40; 60-month OS 82% vs. 61.0%) than in APIC-positive participants (HR, 0.79; 60-month OS, 62.8% vs. 57.6%).

conclusionsThe presence of APIC-negative disease identified participants with a major improvement in OS with the addition of enzalutamide to ADT compared with the addition of NSAA.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsArtificial IntelligenceBenzamidesBiomarkers, TumorNitrilesPhenylthiohydantoinProstatic NeoplasmsAgedAndrogen AntagonistsDocetaxelHumansMaleMiddle AgedAndrogen AntagonistsBenzamidesBiomarkers, TumorDocetaxelenzalutamideNitrilesPhenylthiohydantoin

Identifiers

PMID42360803
PMCPMC13669734

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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.