Optimal Selection of Patients with Genitourinary Cancers for Anti-PD1/PD-L1 Treatment with a Focus on Urothelial and Renal Cell Carcinoma

Abstract

Despite the recent approval of numerous immune checkpoint inhibitors (ICIs) for the treatment of genitourinary tumors, predictive biomarkers are still lacking. Different approaches are necessary, as the only approved biomarker for urothelial carcinoma (UC), namely PD-L1 immunostaining, has questionable predictive value. By contrast, tumor-infiltrating cells have been associated with therapy response in both UC and renal cell carcinoma. Tumor-derived gene signatures can further identify patients with pre-existing adaptive immunity. Whereas tumor mutation burden, DNA repair defects, and microsatellite instability are of some predictive value, the utility of single gene mutations has not yet been proved. As ICIs mainly target tumor metastases, analysis of primary tumors appears to be suboptimal. Circulating biomarkers reflecting tumor and systemic alterations in a more complex and dynamic manner are of great potential. The most promising approach is an analysis of complex tumor composition with concomitant consideration of the host immune status, which is also influenced by the gut microbiome. PATIENT SUMMARY: Immunotherapy is one of the treatment options for cancers of the urinary tract and kidney. We review the methods for measuring biomarkers that may predict which patients are most likely to respond to this treatment.

Keywords: Biomarker; Checkpoint inhibitor; Genitourinary caner; Kidney cancer; Tumor therapy; Urothelial carcinoma.