# PROPHECY: prospective multicentre validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer

Source: https://onco.cc/key-papers/paper-prophecy-arv7-validation-jco-2019/  
OnCo record `paper-prophecy-arv7-validation-jco-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A blinded study across several hospitals confirmed that men whose circulating tumour cells carry the shortened androgen receptor live less long on hormone tablets, on two different tests that agree with each other four times in five.

## Summary

PROPHECY was a multicentre, prospective, blinded study of men with high-risk metastatic castration-resistant prostate cancer starting abiraterone acetate or enzalutamide. The primary objective was to validate the prognostic significance of baseline circulating tumour cell AR-V7 using the Johns Hopkins University modified AdnaTest messenger RNA assay and the Epic Sciences nuclear-specific AR-V7 protein assay. One hundred and eighteen men were enrolled. AR-V7 detection by both assays was independently associated with shorter progression-free survival, hazard ratios 1.9 and 2.4, and with shorter overall survival, hazard ratios 4.2 and 3.5, after adjusting for circulating tumour cell number and clinical prognostic factors. AR-V7-positive men had confirmed PSA responses in 0 to 11% and soft-tissue responses in 0 to 6%. The observed percentage agreement between the two assays was 82%.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of Clinical Oncology
- Year: 2019
- DOI: 10.1200/JCO.18.01731
- Authors: Armstrong AJ, Halabi S, Luo J, et al.
- Findings: Independent association with shorter progression-free survival on both assays (hazard ratios 1.9 and 2.4).; Independent association with shorter overall survival (hazard ratios 4.2 and 3.5).; Confirmed PSA responses in 0 to 11% of AR-V7-positive men.; Agreement between the two assays 82%.
- What it means: It turned a single-centre observation into a prospectively validated one and concluded that AR-V7-positive men should be offered alternatives to abiraterone and enzalutamide. It also quantified the honest limit: two assays for the same analyte disagree on nearly one sample in five.
- Caveats: A high-risk enriched population, so the prevalence does not generalise to all castration-resistant disease.; Prognostic and not, on its own, a randomised demonstration that changing treatment helps.; Still not in any label, and available only at specialist centres.

## Sources

- Armstrong et al., J Clin Oncol 2019: PROPHECY, prospective multicentre validation of circulating tumour cell AR-V7 in 118 men with high-risk mCRPC: https://doi.org/10.1200/JCO.18.01731
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30865549/

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Intravasation & circulating tumour cells](https://onco.cc/pathways/intravasation-ctc-survival/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/), [RNA splicing](https://onco.cc/pathways/rna-splicing/)
- terms: [AR-V7 splice variant](https://onco.cc/terms/ar-v7/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [PSA50 / PSA90 response](https://onco.cc/terms/psa50/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- biomarkers: [AR-V7 splice variant](https://onco.cc/biomarkers/ar-v7-splice-variant/)

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