scholarly journals New Settings for Immune Checkpoint Inhibitors in Urothelial Cancer

2021 ◽  
Vol 19 (5.5) ◽  
pp. 629-632
Author(s):  
Arlene O. Siefker-Radtke
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Urothelial Bladder Cancer ◽  
Nccn Guidelines ◽  
Response To Chemotherapy ◽  
Urothelial Bladder ◽  
Muscle Invasive

The advent of immune checkpoint inhibitors (ICIs) has changed the game in cancer immunotherapy, specifically in the treatment of urothelial bladder cancer. Several clinical trials combining chemotherapy with ICIs have resulted in approvals from the FDA and subsequent revisions within the NCCN Guidelines. The current NCCN Guidelines for Bladder Cancer reflect the most up-to-date, evidence-based data relating to the evaluation and management of urothelial bladder cancer. ICIs have been incorporated into the guidelines as maintenance therapy in response to chemotherapy, sequencing after disease progression from frontline chemotherapy, and for the treatment of non–muscle-invasive bladder cancer.

Neoadjuvant or adjuvant immunotherapy in bladder cancer: biological opportunity or clinical utility?

2021 ◽  
pp. 030089162110616
Author(s):  
Fausto Petrelli ◽  
Gianluca Perego ◽  
Ivano Vavassori ◽  
Andrea Luciani
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Of The Bladder ◽  
Muscle Invasive

In urothelial cancer of the bladder, the introduction of immunotherapy with immune checkpoint inhibitors represents progress in the management of the disease’s early and advanced stages. In particular, recent studies have implemented these drugs in the neoadjuvant and adjuvant phases to treat muscle-invasive bladder cancer. In some studies, patients received neoadjuvant immune checkpoint inhibitors alone (PURE and ABACUS) to treat muscle invasive bladder cancer, whereas other studies provided this therapy to cisplatin-ineligible patients. Furthermore, a large Phase III study (CheckMate 247) compared placebo with adjuvant nivolumab therapy in patients with high-risk urothelial cancer after neoadjuvant chemotherapy and surgery or surgery alone. Despite some uncertain niches (nonbladder, PD-L1-negative tumors, and node-negative resected cancers), certain biological opportunities (exploring new targets, evaluating in vivo pathologic response, focusing on biomarkers for response) and clinical uses (avoiding chemotherapy at all or in frail patients, attaining similar pathologic complete response rates as in cisplatin-based chemotherapy) are valid reasons for incorporating these agents into the therapeutic armamentarium of medical uro-oncologists.

scholarly journals Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4411
Author(s):  
Giandomenico Roviello ◽  
Martina Catalano ◽  
Raffaella Santi ◽  
Valeria Emma Palmieri ◽  
Gianmarco Vannini ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Locally Advanced ◽  
High Morbidity ◽  
Future Perspectives ◽  
Urothelial Bladder ◽  
Muscle Invasive

Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Urothelial carcinoma in the era of immune checkpoint inhibitors

Immunotherapy ◽  
2021 ◽  
Author(s):  
Nadine Khalife ◽  
Claude Chahine ◽  
Manal Kordahi ◽  
Tony Felefly ◽  
Hampig Raphael Kourie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Disease ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Muscle Invasive

Bladder cancer is the seventh most frequent cancer worldwide. The majority of patients present with nonmuscle invasive disease, while 20% of the patients are diagnosed with muscle-invasive bladder cancer. The treatment of nonmuscle invasive disease is endoscopic resection followed by intravesical adjuvant treatment for high risk patients. The standard treatment of localized muscle-invasive disease is neoadjuvant chemotherapy followed by radical cystectomy. Platinum-based chemotherapy is the first-line treatment in locally advanced or metastatic urothelial carcinoma. Immune checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma as second-line treatment or first-line in platinum-ineligible patients. Recently, pembrolizumab have been approved in BCG-refractory nonmuscle invasive bladder cancer. This review summarizes the current evidence concerning immunotherapy in the treatment of urothelial carcinoma.

scholarly journals Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Franklin C. Lee ◽  
William Harris ◽  
Heather H. Cheng ◽  
Jaideep Shenoi ◽  
Song Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Cancer ◽  
Response Rates ◽  
Complete Response ◽  
Pathologic Response ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Alternative Regimen

Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC) versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) in the neoadjuvant setting.Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0) and any response (≤pT1). Odds ratios were calculated using multivariate logistic regression.Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64),P=0.03) and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64),P=0.01). Seventy-two patients received GC (n=41) or MVAC (n=31). CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58). Any response (≤pT1) was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71).Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC). Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

Bladder preservation therapy for muscle invasive bladder cancer: the past, present and future

2020 ◽  
Vol 50 (10) ◽  
pp. 1097-1107
Author(s):  
Tomokazu Kimura ◽  
Hitoshi Ishikawa ◽  
Takahiro Kojima ◽  
Shuya Kandori ◽  
Takashi Kawahara ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
The Past ◽  
Muscle Invasive

Abstract Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.

scholarly journals Management of Urothelial Bladder Cancer in Clinical Practice: Real-World Answers to Difficult Questions

2019 ◽  
Vol 15 (8) ◽  
pp. 421-428 ◽  
Author(s):  
Nataliya Mar ◽  
Farshid Dayyani
Keyword(s):  
Bladder Cancer ◽  
Clinical Practice ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Response To Treatment ◽  
Urothelial Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Gray Areas

Management of urothelial bladder cancer has historically been challenging as a result of a limited grasp of disease biology and few available systemic therapy options, mainly consisting of platinum-based chemotherapy. Improved understanding of molecular mechanisms underlying pathogenesis of muscle-invasive bladder cancer as well as their correlation with tumor behavior and response to treatment has emerged over the past few years. Remarkable therapeutic advances have been made with the introduction of checkpoint inhibitors, which have changed the course of this disease. Multiple agents with novel mechanisms of action are also actively being explored in ongoing clinical trials. These advances are exciting but may prove challenging in terms of how to apply this constantly evolving plethora of data to actual patients. This review addresses the gray areas and challenging questions that frequently arise in clinical practice.

scholarly journals Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

2020 ◽  
Vol 18 (3) ◽  
pp. 329-354 ◽  
Author(s):  
Thomas W. Flaig ◽  
Philippe E. Spiess ◽  
Neeraj Agarwal ◽  
Rick Bangs ◽  
Stephen A. Boorjian ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Practice ◽  
Urothelial Carcinoma ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Urothelial Bladder Cancer ◽  
Nccn Guidelines ◽  
Urothelial Bladder ◽  
Biomarker Testing ◽  
Muscle Invasive

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

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