Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer

2021 ◽  
Author(s):  
A. Gordon Robertson ◽  
Khyati Meghani ◽  
Lauren Folgosa Cooley ◽  
Kimberly A. McLaughlin ◽  
Leigh Ann Fall ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Pathologic Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

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.

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.

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 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.

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 Management of Localized Muscle-Invasive Bladder Cancer from a Multidisciplinary Perspective: Current Position of the Spanish Oncology Genitourinary (SOGUG) Working Group

2021 ◽  
Vol 28 (6) ◽  
pp. 5084-5100
Author(s):  
Antonio Gómez Caamaño ◽  
Ana M. García Vicente ◽  
Pablo Maroto ◽  
Alfredo Rodríguez Antolín ◽  
Julián Sanz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Working Group ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Clinical Staging ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Selection Of Patients ◽  
Selection Of

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

Predictors of pathologic response after radical cystectomy for muscle invasive bladder cancer: A population-based analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 503-503
Author(s):  
Shane M. Pearce ◽  
Akbar Ashrafi ◽  
Matthew Winter ◽  
Saum Ghodoussipour ◽  
Daniel Zainfeld ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Clinical Stage ◽  
Multivariable Analysis ◽  
Pathologic Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Academic Center ◽  
Muscle Invasive ◽  
Over Time

503 Background: Neoadjuvant chemotherapy (NAC) improves overall survival (OS) for patients with muscle invasive bladder cancer (MIBC) undergoing radical cystectomy (RC), possibly through an increase in pathologic complete response (CR), defined as a pathologic stage T0 (pT0). We sought to identify predictors of CR for MIBC. Methods: The National Cancer Database from 2004 to 2013 was used to identify patients with cT2-4cN0cM0 urothelial cell carcinoma treated with RC. Patients were grouped based on pathology as CR (pT0), partial response (PR – pTa/Tis/T1) or no response (NR - pT2 or higher). Predictors of NAC and CR were identified with multivariable logistic regression. Cox proportional hazards model was used to compare OS based on cT stage, receipt of NAC and pathologic response. Results: The study population included 10,820 patients and NAC was administered in 16.4%. Use of NAC was associated with higher cT stage (p < 0.01) and increased over time (10% from 2003-2007 vs. 24% from 2011-2013, p < 0.01). Predictors of NAC use on multivariable analysis include younger age, lower comorbidity score, treatment at an academic center, and diagnosis from 2011-2013 (p < 0.01). Overall, CR was achieved in 3.3% without NAC and 16.3% with NAC (p < 0.01). NAC improved 5-year OS for all cT stages, however the survival benefit was only observed among those achieving CR (p < 0.01). Multivariable Cox regression demonstrates that both PR (HR 0. 58, p < 0.01) and CR (OR 0.26, p < 0.01) were independently associated with improved OS among those treated with NAC. Multivariable analysis identified age (OR 0.98, p < 0.01) and increased clinical stage (cT3: OR 0.47, p < 0.01; cT4 OR 0.54, p < 0.01) as negative predictors of CR. Utilization of NAC (OR 4.82 p < 0.01), academic institution, and diagnosis 2011-2013 (OR 1.92, p < 0.01) increased the odds of CR. Conclusions: Use of NAC increased over time and CR occurred in 16% of patients who received NAC. Treatment at an academic center, diagnosis from 2011-2013 and use of NAC were independently associated with CR, while increased age and clinical stage were negative predictors of CR. PR and CR are independently associated with improved OS relative to non-responders.

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