Evidence map›Paper›PMID 41922546›Full record

ArticleProstate cancer and prostatic diseases2026

Cytoplasmic versus nuclear localization of androgen receptor splice variant 7 as a predictor of benefit from androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (PROPHECY trial).

Santosh Gupta, Siyuan Guo, Susan Halabi, Chenxi Yu, Hyotae Kim, Jane McKenzie, Daniel J George, David M Nanus, Russell Z Szmulewicz, Daniel C Danila and 3 more

Registry-linked trialAbstract read
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In one paragraph

Article in Prostate cancer and prostatic diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02269982 (Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT02269982 completednot on this map

Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)

TypeobservationalSponsorDuke UniversityRan2015 to 2019Enrolled120ConditionsProstate CancerArmsAR-v7 assays
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

13 authors.

Santosh GuptaEpic Sciences, San Diego, CA, USA. stanford14santosh@gmail.com.ORCID http://orcid.org/0000-0002-5294-8245
Siyuan GuoDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Susan HalabiDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-4135-2777
Chenxi YuDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-3452-9095
Hyotae KimDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Jane McKenzieDepartment of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-2126-2838
Daniel J GeorgeDepartment of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-0836-8542
David M NanusWeill Cornell Medical College, New York, NY, USA.
Russell Z SzmulewiczUniversity of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1444-3617
Daniel C DanilaMemorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7647-0741
Jun LuoJames Buchanan Brady Urological Institute, Dept. of Urology, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1414-473X
Emmanuel S AntonarakisMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Andrew J ArmstrongDepartment of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. andrew.armstrong@duke.edu.ORCID http://orcid.org/0000-0001-7012-1754

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAndrogen receptor splice variant-7 (AR-V7), a constitutively active truncated protein, is linked to hormone therapy resistance. Nuclear AR-V7 in CTCs correlates with poor response and shorter progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) treated with ARPIs. The predictive value of cytoplasmic AR-V7 localization remains unclear. This exploratory study evaluated whether an AR-V7-agnostic CTC scoring criterion, including cytoplasmic detection, better predicts ARPI in this mCRPC setting.

methodsBaseline blood from 107/118 pre-ARPI mCRPC patients in the PROPHECY trial (NCT02269982) was analyzed for nuclear and cytoplasmic AR-V7 using Epic's CTC platform. Associations with confirmed PSA50 response, OS, and PFS with abiraterone or enzalutamide treatment were examined. Correlations between AR overexpression, AR-V7 localization, and AR-V7 mRNA levels were assessed. Proportional hazards models adjusted for Halabi risk score and CellSearch CTC count (>5) evaluated cytoplasmic AR-V7 prognostic significance.

resultsAt baseline, 10% (11/107) had nuclear-localized AR-V7 and 14% (15/107) had cytoplasmic-only AR-V7, totaling 24% AR-V7-positive. All nuclear AR-V7 cases showed AR overexpression vs. 67% of cytoplasmic-only cases. PSA50 responses occurred in 0% nuclear, 13% cytoplasmic-only, and 30% AR-V7-negative patients. Cytoplasmic AR-V7+ patients had worse PFS and OS than AR-V7- patients, but similar PFS compared with nuclear AR-V7 + , despite numerically better PSA declines and OS.

conclusionsCytoplasmic-only AR-V7 is more prevalent than nuclear AR-V7 in mCRPC and is associated with poor PFS and intermediate PSA and OS outcomes. Assessing both nuclear and cytoplasmic AR-V7 in CTCs may improve risk stratification before ARPI therapy. CLINICAL SIGNIFICANCE: This study clarifies the clinical relevance of cytoplasmic AR-V7 in circulating tumor cells from men with metastatic castration-resistant prostate cancer. While nuclear-localized AR-V7 predicts extremely poor response, PFS, and overall survival with AR pathway inhibitors, cytoplasmic AR-V7 expands the definition of AR-V7-positive status and identifies patients with equally poor PFS and intermediate response and overall survival outcomes. Assessing both nuclear and cytoplasmic AR-V7 fractions may thus improve risk stratification heterogeneity and could better guide poor-risk ARPI treatment decisions by avoiding ineffective ARPI treatment, helping personalize therapy, and improving outcomes in men with mCRPC.

Identifiers

PMID41922546

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