Immunotherapy in Genitourinary Malignancy: Evolution in Revolution or Revolution in Evolution

Immunotherapy, the 5th pillar of cancer care after surgery, radiotherapy, cytotoxic chemotherapy, and precision therapy (molecular targeted therapy), is revolutionizing the standard of care in certain patients with genitourinary malignancies. As modest clinical benefits of IL-2 for metastatic renal cell carcinoma and Bacillus Calmette-Guerin therapy for early-stage bladder cancers in the past years, immune checkpoint inhibitors therapies demonstrate meaningful survival benefit and durable clinical response in renal cell carcinoma, urothelial carcinoma, and some prostate cancer. Despite best efforts, the benefits are limited to a minority of unselected patients due to the complexities of biomarker development. Now come the next hurdles: figuring out which patients best respond to immune checkpoint inhibitors and which patients won't respond to immune checkpoint inhibitors? How best to approach immune checkpoint inhibitors therapies to extend/maximize the treatment response as long as possible? How to overcome therapeutic resistance by specific concurrent immunomodulators or targeted therapy or chemotherapy? The role of immune checkpoint inhibitors in combination or sequencing with chemotherapy or other targeted therapies or other immunomodulating therapeutics in the early disease, neoadjuvant, adjuvant, and metastatic setting is actively under exploration. Ideal strategy for cancer care is to provide not just more time, but more quality time: there remain unmet needs for novel therapies that exploit molecular or genetic pathways to extend survival without compromising health-related quality of life for patients with advanced genitourinary malignancies. Further research is needed to discover new therapeutic strategies, and validate efficacy and effectiveness in real-world settings.