Immune Checkpoint Inhibitors for Urologic Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 10966

Special Issue Editor


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Guest Editor
Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA
Interests: identification of biomarkers for prostate; kidney and bladder cancer; neuroendocrine prostate cancer; PSMA theranostics; upper tract urothelial carcinoma; treatment-resistant urothelial carcinoma; genomics and immunogenomics for urological cancers
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Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit a manuscript to the Special Issue, “Immune Checkpoint Inhibitors for Urologic Cancers”. Urologic malignancies, including prostate, urothelial, kidney and testicular carcinomas, are increasingly diagnosed in Western countries. Despite advances in definitive therapies, metastatic disease remains lethal. The addition of immune checkpoint inhibitors in the armamentarium of current therapeutic modalities in urothelial and kidney cancers has fueled significant research to elucidate the genomic and immunogenomic context of urologic cancers, biomarkers predictive of clinical outcomes and novel therapeutic combinations.

This Special Issue of Cancers welcomes original research articles and reviews related to all aspects of immune checkpoint inhibitor use in urologic cancers.

We are looking forward to receiving your contributions.

You may choose our Joint Special Issue in Current Oncology.

Sincerely,

Dr. Panagiotis Vlachostergios
Guest Editor

Manuscript Submission Information

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Keywords

  • identification of biomarkers for prostate
  • kidney and bladder cancer
  • neuroendocrine prostate cancer
  • PSMA theranostics
  • upper tract urothelial carcinoma
  • treatment-resistant urothelial carcinoma
  • genomics and immunogenomics for urological cancers

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Published Papers (6 papers)

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Research

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10 pages, 397 KiB  
Article
Immune-Related Adverse Events of Genitourinary Cancer Patients, a Retrospective Cohort Study
by John C. Hunting, Logan Deyo, Eric Olson, Andrew T. Faucheux, Sarah N. Price and Thomas W. Lycan, Jr.
Cancers 2024, 16(17), 3045; https://doi.org/10.3390/cancers16173045 - 31 Aug 2024
Cited by 1 | Viewed by 818
Abstract
Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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10 pages, 767 KiB  
Article
Toxicity-Induced Discontinuation of Immune Checkpoint Inhibitors in Metastatic Urothelial Cancer: 6-Year Experience from a Specialized Uro-Oncology Center
by Severin Rodler, Can Aydogdu, Isabel Brinkmann, Elena Berg, Rega Kopliku, Melanie Götz, Troya Ivanova, Alexander Tamalunas, Gerald B. Schulz, Volker Heinemann, Christian G. Stief and Jozefina Casuscelli
Cancers 2024, 16(12), 2246; https://doi.org/10.3390/cancers16122246 - 18 Jun 2024
Cited by 1 | Viewed by 1126
Abstract
Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but [...] Read more.
Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2–55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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Review

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16 pages, 802 KiB  
Review
How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma
by Mathieu Larroquette, Félix Lefort, Charlotte Domblides, Luc Héraudet, Grégoire Robert, Alain Ravaud and Marine Gross-Goupil
Cancers 2024, 16(9), 1780; https://doi.org/10.3390/cancers16091780 - 5 May 2024
Cited by 1 | Viewed by 2266
Abstract
In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- [...] Read more.
In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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14 pages, 758 KiB  
Review
The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors
by Konstantinos Evmorfopoulos, Konstantinos Marsitopoulos, Raphael Karachalios, Athanasios Karathanasis, Konstantinos Dimitropoulos, Vassilios Tzortzis, Ioannis Zachos and Panagiotis J. Vlachostergios
Cancers 2024, 16(2), 428; https://doi.org/10.3390/cancers16020428 - 19 Jan 2024
Cited by 1 | Viewed by 1985
Abstract
Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there [...] Read more.
Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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17 pages, 3412 KiB  
Review
Current Landscape of Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma: Is There a Role for Additional T-Cell Blockade?
by Vanessa Ogbuji, Irasema C. Paster, Alejandro Recio-Boiles, Jennifer S. Carew, Steffan T. Nawrocki and Juan Chipollini
Cancers 2024, 16(1), 131; https://doi.org/10.3390/cancers16010131 - 27 Dec 2023
Cited by 4 | Viewed by 1605
Abstract
Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently [...] Read more.
Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently expressed on T-cells in urothelial carcinoma. The blockade of this immune checkpoint can lead to the reactivation of lymphocytes and augment the anti-tumor immune response. The only immune checkpoint inhibitors that are FDA-approved for metastatic urothelial carcinoma target the programmed death-1 receptor and its ligand (PD-1/PD-L1) axis. However, the overall response rate and progression-free survival rates of these agents are limited in this patient population. Therefore, there is a need to find further immune-bolstering treatment combinations that may positively impact survival for patients with advanced UC. In this review, the current immune checkpoint inhibition treatment landscape is explored with an emphasis on combination therapy in the form of PD-1/PD-L1 with CTLA-4 blockade. The investigation of the current literature on immune checkpoint inhibition found that preclinical data show a decrease in tumor volumes and size when PD-1/PD-L1 is blocked, and similar results were observed with CTLA-4 blockade. However, there are limited investigations evaluating the combination of CTLA-4 and PD-1/PD-L1 blockade. We anticipate this review to provide a foundation for a deeper experimental investigation into combination immune checkpoint inhibition therapy in metastatic urothelial carcinoma. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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Other

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17 pages, 3156 KiB  
Systematic Review
The Efficacy and Safety of Immune Checkpoint Inhibitors in Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis
by Obada Ababneh, Alina Ghazou, Mohmmad Alawajneh, Saleh Alhaj Mohammad, Abdullah Bani-Hani, Nasr Alrabadi and Aditya Shreenivas
Cancers 2024, 16(5), 900; https://doi.org/10.3390/cancers16050900 - 23 Feb 2024
Cited by 1 | Viewed by 2502
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10–19%, I2 = 0%), and the DCR was 43% (95% CI = 37–50%, I2 = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85–23.05), and the median PFS was 2.8 months (95% CI = 1.8–5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)
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