scholarly journals Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 769
Author(s):  
Arthur Peyrottes ◽  
Idir Ouzaid ◽  
Gianluigi Califano ◽  
Jean-Francois Hermieu ◽  
Evanguelos Xylinas
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Response Rate ◽  
Checkpoint Inhibitor ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Neoadjuvant Immunotherapy ◽  
Muscle Invasive

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

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 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.

scholarly journals Biomarkers in Bladder Cancer Surveillance

2021 ◽  
Vol 8 ◽  
Author(s):  
Sukumar S. Sugeeta ◽  
Anand Sharma ◽  
Kenrick Ng ◽  
Arvind Nayak ◽  
Nikhil Vasdev
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Prospective Studies ◽  
Urine Cytology ◽  
Cancer Surveillance ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Protein Biomarkers ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays.Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade.Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated.Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use.Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

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.

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