Immune Checkpoint Inhibitors (ICI) in Urological Cancers - A New Modern Era - but Not Generally Applied

Sep 23, 2026

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The modern era of systemic therapy for urological cancers is strongly shaped by immune checkpoint inhibitors, which have transformed oncology over the past three decades, particularly in chemoresistant settings. This review synthesizes evidence from electronic databases to describe the natural history and trajectories of clinical trials in urological malignancies. While many studies broaden clinician experience and in some cases improve prognosis and overall survival, certain trials proved to be ineffective blind alleys for systemic treatment. The article concludes with future directions toward combination strategies with targeted therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

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Introduction

History and Molecular Mechanism of Checkpoint Inhibitors

Review Immune Checkpoint Inhibitors (ICI) in Urological Cancers: A New Modern Era, but Not Generally Applied Marcin Sokołowski 1,2, *, Anna Sokołowska 1, Magdalena Chrza˛szcz 1 and Aleksandra Butrym 1,3 Academic Editor: Takuya Noguchi Received: 25 June 2025 Revised: 14 July 2025 Accepted: 16 July 2025 Published: 25 July 2025 Corrected: 16 September 2025 Citation: Sokołowski, M.; Sokołowska, A.; Chrza˛szcz, M.; Butrym, A. Immune Checkpoint Inhibitors (ICI) in Urological Cancers: ANew Modern Era, but Not Generally Applied. Int. J. Mol. Sci. 2025, 26, 7194 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26157194 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Dr Alfred Sokołowski Specialist Hospital in Walbrzych, 58-309 Walbrzych, Poland; [annabiernacka7@gmail.com](annabiernacka7@gmail.com) (A.S.); [lek.mmch@gmail.com](lek.mmch@gmail.com) (M.C.); [aleksandra.butrym@gmail.com](aleksandra.butrym@gmail.com) (A.B.) 2 Lower Silesian Oncology, Pulmonology and Hematology Center, pl. Hirszfelda 12, 53-413 Wroclaw, Poland 3 Department of Cancer Prevention and Therapy, Wroclaw Medical University, ul Borowska 2-13, 50-556 Wroclaw, Poland * [Correspondence: maxsokolonko@gmail.com or marsok1@zdrowie.walbrzych.pl](Correspondence: maxsokolonko@gmail.com or marsok1@zdrowie.walbrzych.pl); Tel.: +48-609-495-094 Abstract The modern era of systemic treatment of urological cancers is definitely marked by checkpoint inhibitors. Over the past 30 years, checkpoint inhibitors have changed the oncological world, especially in chemoresistant malignancies. Multiple investigations focused on immunotherapy in urological cancers have carved new paradigms and changed clinical guidelines. However, some clinical trials have been blind alleys for systemic therapy. After a scrutinized review of electronic databases, we want to present the natural history and courses of clinical trials in urological malignancies. All of them contribute to expanding the knowledge and experience of clinicians, and some of them improve the prognosis and prolong the overall survival of oncological patients. In conclusion, checkpoint inhibitors open a new modern era in some urological cancers, but not overall. Future perspectives are focused on combination with targeted therapy and could be a new way forward in the systemic treatment of urological cancers. Keywords: immunotherapy; checkpoint inhibitors; urological cancers 1. Introduction Urological cancers, such as renal cell cancer (RCC), urothelial cancer (UC), prostate cancer, and germ cell tumors, are global and social challenges in the modern era of systemic therapy. RCC is a disease with a rising worldwide incidence, estimated at 400,000 new cases annually, and a mortality rate approaching 175,000 deaths per year [1] . UC is the tenth most common cancer in the world, with approximately 500,000 new cases and over 210,000 deaths in 2020 [2] . The World Health Organization (WHO) estimates prostate cancer as the third most common diagnosed malignancy, with 1,414,259 cases globally [2] . Germ cell tumors, especially testicular cancer, recorded 74,458 new cases and almost 10,000 deaths worldwide, as estimated by the International Agency for Research of Cancer (IARC) [3] . Systemic therapy—defined as the use of a substance that travels through the bloodstream, reaching and affecting cells—consists of different combinations of chemotherapy, immunotherapy and targeted therapy. In our review, we want to briefly present and summarize the most important clinical trials, focused on immune checkpoint inhibitors (ICI), which have significantly changed the prognosis and natural co

FAQs

Which urological cancers are discussed in the review's introduction?

The introduction highlights renal cell cancer, urothelial cancer, prostate cancer, and germ cell tumors, describing their global burden and relevance to systemic therapy.

How does the review describe the historical origin of immune checkpoint inhibitors?

It traces the work beginning in 1992 with research by Tasuku Honjo’s group identifying PD-1, followed by later studies clarifying PD-1’s role and its interactions with ligands such as PD-L1.

What does the review conclude about checkpoint inhibitors in urological cancers?

Checkpoint inhibitors are presented as opening a new modern era in some urological cancers, but not broadly across all settings, with future perspectives emphasizing combinations with targeted therapy.

Sep 23, 2026

Uploaded by Pentious