Association of Prior 5-Alpha-Reductase Inhibitor Exposure With Immune Checkpoint Inhibitor Benefit in Metastatic Renal Cell Carcinoma: Multicenter Cohort With Single-Cell Immune Profiling

The study investigates the impact of prior 5-α-reductase inhibitor (5-ARI) exposure on the effectiveness of immune checkpoint inhibitors (ICIs) in 185 patients with metastatic renal cell carcinoma (mRCC). The results indicate that patients with at least 12 months of 5-ARI use before ICI treatment had significantly better outcomes, including higher objective response rates (59.8% vs 39.8%) and improved progression-free and overall survival rates. The study also found that these patients experienced earlier and longer-lasting responses without an increase in severe adverse events. Single-cell RNA sequencing revealed a more favorable immune environment in 5-ARI-exposed patients, characterized by reduced regulatory T cells and lower exhaustion of CD8⁺ T-cells. These findings suggest that 5-ARI pre-treatment may enhance ICI efficacy and support further trials on androgen-axis modulation as a cost-effective adjunct to immunotherapy.