The immunotherapy revolution in genitourinary malignancies.
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ABSTRACT:
SUBMITTER: U Gandhy S
PROVIDER: S-EPMC7466927 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE OF REVIEW:Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary malignancies including prostate cancer, renal cell carcinoma, and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of genitourinary malignancies are highlighted in this review. RECENT FINDINGS:Dramatic responses to checkpoint inhibitor therapy have been demonstrated in renal cell carcinoma and bladder cancer with recent Food and Drug Administration approvals in both indications. No benefit to checkpoint inhibitor therapy has yet been shown for the management of prostate cancer. Therapeutic cancer vaccines have also shown benefit in the treatment of genitourinary malignancies, specifically in the treatment of prostate cancer. Despite advances in these therapeutic modalities, benefit is limited to a subset of patients. SUMMARY:Current evidence supports the use of immune checkpoint inhibitor therapy and therapeutic cancer vaccines for the management of genitourinary malignancies. Further development of biomarkers for predicting response and study of combination therapy is required to achieve optimal efficacy with these therapeutic interventions.
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Project description:Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
| S-EPMC5402074 | biostudies-literature
Project description:Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo. The immune checkpoint inhibitor nivolumab (anti-PD-1) recently received FDA approval for the management of patients with advanced RCC patients previously treated with anti-angiogenic therapy, based on OS benefit compared to everolimus. Recently, large clinical trials demonstrated meaningful clinical benefit, including durable responses, as well as a good tolerability/safety profile with the use of immune checkpoint inhibitors in advanced RCC and chemotherapy-resistant advanced urothelial carcinoma (UC), while FDA just approved atezolizumab for platinum-treated advanced UC. Numerous interesting trials in different cancers are ongoing. Several combinations of immune checkpoint blockade with chemotherapeutics, vaccines, targeted tyrosine kinase inhibitors & monoclonal antibodies, epigenetic modifiers, anti-angiogenic agents, tumor microenvironment & myeloid cell targeting therapies, metabolic modification strategies, radiation, and others, are being tested in clinical trials. Comprehensive understanding of the factors underlying antitumor immune responses in physiologically relevant animal models and humans will refine further the clinical benefit of immunotherapy. Discovery and validation of appropriate molecular biomarkers via coordinated translational research efforts, rational clinical trial designs with suitable endpoints and well-defined eligibility criteria, prospective registries/databases, careful evaluation of cost-effectiveness and safety/tolerability, adequate funding and open continuous discussions among all stakeholders will support the revolutionary nature of immunotherapy in GU cancers.
| S-EPMC4971374 | biostudies-literature
Project description:A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types. In genitourinary malignancies, immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma; however, these treatments have not yet proven broadly beneficial for patients with metastatic prostate cancer. Numerous prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint inhibition. This perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal, urothelial, and prostate cancers.
| S-EPMC6333044 | biostudies-literature
Project description:Immunotherapy drugs have recently been approved by the Food and Drug Administration for the treatment of several genitourinary malignancies, including bladder cancer, renal cancer, and prostate cancer. Preclinical data and early clinical trial results suggest that immune checkpoint inhibitors can act synergistically with radiation therapy to enhance tumor cell killing at local irradiated sites and in some cases at distant sites through an abscopal effect. Because radiation therapy is commonly used in the treatment of genitourinary malignancies, there is great interest in testing the combination of immunotherapy with radiation therapy in these cancers to further improve treatment efficacy. In this review, we discuss the current evidence and biological rationale for combining immunotherapy with radiation therapy, as well as emerging data from ongoing and planned clinical trials testing the efficacy and tolerability of this combination in the treatment of genitourinary malignancies. We also outline outstanding questions regarding sequencing, dose fractionation, and biomarkers that remain to be addressed for the optimal delivery of this promising treatment approach.
| S-EPMC8141854 | biostudies-literature
Project description:The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants. Despite impressive early trials, vaccine monotherapy has achieved limited success in the clinical world; however, combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine stimulation are expected to move the field forward. This article reviews pivotal trials of cancer vaccines in prostate, renal, and bladder cancer and ongoing trials combining vaccines with other immune therapy agents.
| S-EPMC6161030 | biostudies-literature
Project description:Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers.
| S-EPMC7194001 | biostudies-literature
Project description: Not available
| S-EPMC8575561 | biostudies-literature
Project description: Not available
| S-EPMC8261419 | biostudies-literature
Project description:PurposeRecent advances in molecular biology technology have allowed identification of microbial communities in the urinary tract, and urinary microbiome is associated with various urological diseases. In this study, we aimed to characterize the urinary microbiome of genitourinary malignancies.Materials and methodsMetagenomic analysis of urinary DNA was performed in 85 patients including 30 with bladder cancer (BC), 27 with prostate cancer (PC), 12 with renal cancer (RC), and 16 with non-cancer (NC). 16S rRNA gene sequencing was conducted after amplification of the V3-V4 region.ResultsPC and RC had significantly lower Shannon index than BC, and beta diversity showed significantly different microbiome composition between four groups. We identified six genera of Cutibacterium, Peptoniphilus, Sphingomonas, Staphylococcus, Micrococcus, and Moraxella, which showed significantly different abundance between the four groups. When each of the malignancies were compared to NC at the species level, Micrococcus sp. was significantly increased in BC. We also identified 12 and five species with increased populations in PC and RC, respectively. Of these, Cutibacterium acnes, Cutibacterium granulosum, Peptoniphilus lacydonensis, and Tessaracoccus were significantly increased in both PC and RC.ConclusionsUrinary microbiome composition was different depending on the type of genitourinary malignancies, and we identified bacteria that are significantly associated with each type of malignancy. Specifically, several bacterial species were associated both PC and RC, suggesting that PC and RC share a similar pathogenesis-related urinary microbiome.
| S-EPMC9448674 | biostudies-literature