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.
Project description:Purpose of reviewActive 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 findingsDramatic 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.SummaryCurrent 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.
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.
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.
Project description:The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.
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.