Prevalence and clinical significance of AR-V7 in extra-prostatic malignancies: A systematic review.

Abstract

e15181 Background: Androgen receptor splice variant 7 ( AR-V7 ) is a constitutively active androgen receptor isoform lacking the ligand-binding domain. AR-V7 is a well-established mediator of resistance to androgen receptor (AR) targeting therapies in prostate cancer (PCa). Although AR-V7 has been increasingly reported in non-prostatic malignancies, its prevalence, biological significance, and clinical relevance outside the prostate remain poorly defined. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Major databases and oncology/pathology conference proceedings were searched until October 2025. Studies reporting AR-V7 expression in non-prostatic malignancies were included. Data on cancer type, AR-V7 detection methods, prevalence, treatment context, and clinical outcomes were extracted and synthesized narratively due to methodological heterogeneity. Results: Thirty-four studies encompassing 4855 clinical cases and 60 cancer cell lines were included. Overall, AR-V7 was detected in 948 cases (19.5%). Breast cancer accounted for the largest absolute number of AR-V7 –positive cases (815/948; 86.0%), although its within-cancer prevalence was modest (815/4,057; 20.1%) and highly sensitive to detection methodology. Higher proportional prevalence was observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non–muscle-invasive bladder carcinoma (82.6%). AR-V7 was mostly detected in treatment-naïve cancers across several malignancies. Across breast cancer cell lines, AR-V7 expression was exclusive to AR-positive contexts and commonly co-existed with additional splice variants. Conclusions: AR-V7 is detectable across multiple non-prostatic malignancies, with marked heterogeneity by cancer type and detection method. Unlike prostate cancer, where AR-V7 typically emerges as a mechanism of acquired resistance after androgen-directed therapy, AR-V7 is present in a substantial subset of treatment-naïve extra-prostatic cancers, supporting its role as an intrinsic, tumor-specific molecular feature. Larger, prospective studies are warranted to define its prognostic and predictive utility to refine future AR-targeted strategies in precision oncology. Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251083307.