Androgen Receptor Expression in Urothelial Bladder Cancer—A Systematic Review and Meta‐Analysis

BACKGROUND: Bladder cancer is a globally prevalent malignancy with a marked male predominance. Over the past decade, the androgen receptor has been investigated as a potential contributor to bladder cancer pathophysiology. Androgen receptor expression is most commonly assessed via immunohistochemistry, but its association with pathological features and clinical outcomes remains uncertain. This meta-analysis aimed to evaluate whether androgen receptor expression assessed by immunohistochemistry is associated with pathological characteristics of urothelial bladder cancer, with exploratory assessment of reported prognostic outcomes. METHODS: A systematic search of MEDLINE, EMBASE and Cochrane was performed between January 1st 2000 and October 31st 2024. Papers comparing AR expression using immunohistochemistry to bladder urothelial cancer specimens stratified by grade, stage, gender and survival outcomes were included. RESULTS: In total 16 papers were included with 2108 patient samples. No correlation was found between androgen receptor expression and grade (OR 0.83, 95% CI 0.43-1.59), stage (OR 0.94, 95% CI 0.38-2.35), progression free survival (HR 0.84, 95% CI 0.45-1.59) or recurrence free survival (HR 0.81, 95% CI 0.49-1.31). Male bladder cancer specimens were more likely to express the androgen receptor than female bladder cancer specimens (OR 1.40, 95% CI 1.03-1.89). CONCLUSION: Immunohistochemistry as a measure of androgen receptor expression does not show a consistent association with pathological features and demonstrates no reproducible prognostic signal in the available literature. Male bladder cancer specimens express AR more frequently than female bladder cancer specimens. The significance of this needs to be correlated to further research into normal androgen receptor expression patterns in the urinary bladder and more precise measures of androgen receptor activity than immunohistochemistry.