Current and Future Applications of Novel Immunotherapies in Urological Oncology: A Critical Review of the Literature

Context: Immunotherapies promote anticancer responses with varying levels of success based on the tumor type. Objective: In this narrative review article, we searched the literature regarding immunotherapies in genitourinary malignancies to define the state of the field, explore future applications of immune checkpoint inhibitors, cytokines, vaccines, and cellular therapies in urological oncology and evaluate possible strategies to improve the selection of patients who might benefit from such approaches. Evidence acquisition: We reviewed related literature, with a focus on recent studies about immunotherapies, predictors of response, and ongoing clinical trials. Evidence synthesis: Immunotherapies based on immune checkpoint blockade are approved as first- and second-line therapies for urothelial carcinoma (UC) and second-line therapies for renal cell carcinoma with limited success in prostate cancer. Programmed death-ligand 1 is the most commonly used predictive biomarker outside of UC; however, a substantial proportion of patients with tumors negative for programmed death-ligand 1 expression benefit from checkpoint inhibition, limiting its sensitivity. A high mutational load and molecular subtypes of UC are emerging as additional potential predictors. Genomic sequencing and gene expression analysis associate alterations of genes implicated in DNA repair pathways, such as BRCA1 and BRCA2, with immune checkpoint therapies. In prostate cancer, the vaccine, sipuleucel-T, is the only Food and Drug Administration-approved immunotherapy. Conclusions: Immunotherapies are emerging as exciting new treatment options with a tolerable toxicity profile in urological cancers. Checkpoint inhibitors are effective only in a subset of patients, demanding personalized approaches that consider various clinical and molecular parameters to predict patient response. Clinical trials investigating the optimal timing, sequence, and combination of immunotherapies with standard of care and novel agents will guide therapy choices and improve patient outcome. Patient summary: Clinical data supports the safety and efficacy of immune checkpoint inhibitors alone or in combination with other therapies in urological cancers. Immunotherapies are approved as first-line and second-line treatments in urological cancers. Genomic analysis of renal cell carcinoma and prostate cancer and molecular subtyping of urothelial cancer might guide the selection of patients who might benefit from checkpoint inhibitors.