Abstract

Simple SummaryGenitourinary malignancies include cancers along the urinary tract and the male reproductive tract, encompassing the adrenal glands, kidneys, bladder, prostate, and testicles. Immunotherapy, which treats cancer by using the immune system to attack malignant cells, has historically been successful in treating some types of genitourinary cancers, especially of the bladder and kidney. In the past decade, a more precise method of immunotherapy, known as immune checkpoint inhibition, has gained popularity as it enhances the immune system’s ability to recognize and destroy tumor cells. Several immune checkpoint inhibitors have achieved success in patients with advanced genitourinary cancers. This review provides a brief overview of traditional immunotherapies, focuses on how immune checkpoint inhibitors have achieved success in patients with advanced cancers, and investigates the role for immunotherapy in genitourinary malignancies in the future.For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

Highlights

  • Genitourinary (GU) malignancies affect many people worldwide, with millions of new cases diagnosed annually

  • Prognosis was grim for patients who relapsed after first-line platinum therapy due to a lack of available options [60], until immune checkpoint inhibitor (ICI) provided renewed hope and improved patient outcomes in the second-line setting [61]

  • In cohort 2 of IMvigor210 (NCT02108652), 310 patients with locally advanced or metastatic UC who were previously treated with cisplatin-containing chemotherapy and progressed were administered atezolizumab

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Summary

Introduction

Genitourinary (GU) malignancies affect many people worldwide, with millions of new cases diagnosed annually. It has been well established that cancer cells have developed multiple mechanisms to avoid the immune system. This includes downregulation of antigen-presenting complexes via the Major Histocompatibility Complex (MHC) class 1 pathway in tumor cells [3], as well as suppressed host immune activation via regulatory T cells [4]. This article delves into the role of immunotherapy in the treatment of GU malignancies: urothelial, renal, prostate, and other rarer tumors. We summarize selected clinical trials that are complete, those that are still in progress, and those that are about to begin

Immune Checkpoint Inhibitors
ICIs for NMIBC
Neoadjuvant Therapy for MIBC
Adjuvant Therapy for MIBC
Bladder-Sparing Treatments Involving ICIs in MIBC
Metastatic Bladder Cancer
Frontline Use in Combination with Chemotherapy
Frontline Use with Combination of Two ICIs
Variant Histologic Subtypes of Urothelial Carcinoma and Response to ICIs
Kidney Cancer
Combination of Two ICIs
Combination of ICI with Tyrosine Kinase Inhibitor
ICI Monotherapy
Second-Line Immunotherapy
Adjuvant Therapy after Nephrectomy
Non-Clear Cell Renal Cell Carcinoma
Prostate Cancer
Potential Predictive Biomarkers for ICIs
Future Immune Checkpoint Inhibition Trials
Conclusions
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