AUTHOR=Szabados Bernadett , Duncan Sarah , Choy Julia , Jackson-Spence Francesca , Toms Charlotte , Trevisan Giorgia , Berney Daniel M. , Powles Thomas , Ackerman Charlotte 

TITLE=Androgen Receptor Expression Is a Predictor of Poor Outcome in Urothelial Carcinoma

JOURNAL=Frontiers in Urology

VOLUME=2

YEAR=2022

URL=https://www.frontiersin.org/journals/urology/articles/10.3389/fruro.2022.863784

DOI=10.3389/fruro.2022.863784

ISSN=2673-9828

ABSTRACT=<sec><title>Background</title><p>Several preclinical and clinical studies demonstrated a strong correlation between androgen receptor (AR) signaling and bladder tumorigenesis. This study aims to evaluate the prognostic significance of AR expression in metastatic urothelial carcinoma (mUC).</p></sec><sec><title>Methods</title><p>Samples from a phase III trial (LaMB, NCT00949455) which compared maintenance lapatinib versus placebo after completion of first-line platinum-based chemotherapy in patients with HER 1/2-positive mUC of the bladder were collected. Corresponding baseline and follow-up data included patients enrolled in the study and those who screen failed. AR expression was assessed independently by a single pathologist who was blinded to the study. Samples were grouped according to AR expression (negative vs. positive) and correlated with baseline tumor characteristics and survival.</p></sec><sec><title>Results</title><p>Of the 446 screened samples in the LaMB study, 90 were retrospectively analyzed for AR expression. There were no correlations between AR expression and tumor stage (<italic>r</italic> = −0.10), tumor grade (<italic>r</italic> = 0.05) at diagnosis, or subsequent treatment with lapatinib (<italic>r</italic> = −0.04). The median progression-free survival was 6 months (95% CI, 3.20–6.80) in the AR-negative group and 5 months (95% CI, 3.41–6.59) in the AR-positive group [HR 0.54 (95% CI, 0.31–0.92), <italic>p</italic> = 0.02]. Similarly, patients with AR-negative disease had more favorable overall survival (OS) with 16 months (95% CI, 6.6–25.4) and 11 months (95% CI, 7.0–15.0) in the AR-positive group [HR 0.55 (95% CI, 0.31–0.98), <italic>p</italic> = 0.04]. In the multivariate analysis, AR expression was significantly associated with worse OS (<italic>p</italic> = 0.045).</p></sec><sec><title>Conclusions</title><p>AR expression is a predictor of poor outcome and presents a targetable alteration in patients with mUC.</p></sec>