Perioperative therapy in muscle invasive bladder cancer.
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ABSTRACT:
SUBMITTER: Chatterjee A
PROVIDER: S-EPMC8388335 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) are both major causes of morbidity and mortality. At diagnosis, MIBC is more likely to metastasize, but can often be treated with aggressive care. Standard treatment for MIBC patients is radical cystectomy but a select group of these individuals are not candidates for or will decline this treatment. Thus, bladder preservation therapy followed by combined chemoradiation may be considered. Despite the primary surgical management of MIBC, up to half of patients will obtain tumors at distant sites in the end and perioperative platinum-based chemotherapy comprises the standard of care. However, despite these aggressive treatment options, survival is poor and therefore, it is essential to combine local and systemic therapies. Therapeutic modalities contained cancer vaccines, immune checkpoint inhibitors and immunogenic therapy are emerging as alternatives to immunotherapy, and several drugs have recently been approved by the FDA. Currently, several trials of adjuvant immunotherapy based on checkpoint inhibitors that as monotherapy, inhibit the reaction between programmed death-receptor 1 (PD-1) and programmed death-receptor ligand 1 (PD-L1). Or combined therapies mixed with chemotherapy, radiation, or various immunotherapy are ongoing. This review summarizes the current state of immunotherapies and evolution of the chemotherapy landscape for MIBC perioperative treatment. Widespread research is currently being performed to investigate the role of perioperative immune checkpoint inhibition in both the neoadjuvant and adjuvant setting.
| S-EPMC8799279 | biostudies-literature
Project description:Radical cystectomy is the standard of care treatment for patients with localized muscle-invasive bladder cancer (MIBC). However, patients with MIBC experience high rates of relapse despite primary therapy, and perioperative strategy is an important treatment option. Cisplatin-based neoadjuvant chemotherapy was associated with improved prognosis, and adjuvant chemotherapy is also an important option for selected patients. However, perioperative chemotherapy is not effective in some patients. Moreover, the currently recommended perioperative treatment is cisplatin-based chemotherapy; approximately 50% of the patients are ineligilble for cisplatin treatment owing to various reasons such as medical comorbidities, poor performance status, and renal insufficiency. The recent success of treatment with immune checkpoint inhibitors (ICIs) suggests that ICIs is the new standard therapy for patients with metastatic bladder cancer. Furthermore, ICIs showed more favorable toxicity profiles than conventional cytotoxic chemotherapy. These results indicate that ICIs may play a role in the treatment of muscle-invasive disease, and many recent studies have been conducted in a perioperative setting. The present review aims to summarize and discuss the current perioperative strategy of immunotherapy focused on ICIs based on recent ongoing clinical trials.
| S-EPMC7807333 | biostudies-literature
Project description:Bladder cancer ranks as the 10th most common cancer type globally, and muscle-invasive disease accounts for approximately 25% of newly diagnosed bladder cancers. Despite definitive treatment, 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastasis within 2 years, leading to death. Perioperative systemic therapy is generally recommended to control local relapse or distant metastasis after surgical resection for patients with MIBC. Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard treatment to improve oncologic control and survival outcomes. Adjuvant chemotherapy is recommended for patients with pathological T3-4 or positive lymph nodes after radical cystectomy if no neoadjuvant chemotherapy was given. Nonetheless, perioperative systemic therapy is not applied widely because of its toxicity, and less than 25% of patients receive cisplatin-based neoadjuvant chemotherapy. Therefore, the development of predictive biomarkers for neoadjuvant chemotherapy efficacy and alternative effective regimens for cisplatin-ineligible patients are important. Furthermore, recently, novel anticancer agents such as immune checkpoint inhibitors and antibody-drug conjugates have proven survival benefits in the metastatic setting, thereby expanding their therapeutic applications to the perioperative setting for non-metastatic MIBC. Herein, we discuss the current status and future perspectives of perioperative systemic strategies for MIBC.
| S-EPMC10172053 | biostudies-literature
Project description:Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based chemotherapy has been investigated for its ability to reduce the number of deaths from bladder cancer. Insufficient evidence is available to fully support the use of such chemotherapy in the adjuvant setting; however, neoadjuvant cisplatin-based combination chemotherapy has become a standard of care for eligible patients based on the improved disease-specific and overall survival demonstrated in two randomized phase III trials, compared with surgery alone. For patients with disease downstaging to non-MIBC at the time of radical cystectomy as a result of neoadjuvant chemotherapy, outcomes are outstanding, with 5-year overall survival of 80-90%. Nevertheless, the inability to define before treatment the patients who will and those who will not achieve such a response has impeded the achievement of better outcomes for patients with MIBC. High-throughput DNA and RNA profiling technologies might help to overcome this barrier and enable a more-personalized approach to the use of cytotoxic neoadjuvant chemotherapy. In the past 2 years, trial results have demonstrated the unprecedented ability of immune- checkpoint blockade to induce durable remissions in patients with metastatic disease that has progressed after chemotherapy; studies are now urgently needed to determine how best to incorporate this powerful therapeutic modality into the care of patients with MIBC. Herein, we review the evolution of chemotherapy and immunotherapy for muscle-invasive bladder cancer.
| S-EPMC6054138 | biostudies-literature
Project description:ObjectiveWe aim to describe and highlight the current use of immune checkpoint inhibitors (ICIs) in the muscle invasive bladder cancer (MIBC) treatment landscape, particularly focusing on the perioperative setting. We provide a comprehensive review of key trials of the use of ICI in the perioperative setting, discussing trial outcomes and limitations and reviewing the role of biomarkers.IntroductionICIs have recently been integrated into the treatment algorithm for metastatic urothelial carcinoma. More than 30 published studies have investigated the role of these agents in the radical treatment of MIBC. Some studies have demonstrated conflicting results, affecting widespread adoption in clinical practice.MethodsWe performed a narrative overview of the literature from databases including PubMed, MEDLINE, Embase, European society of Medical Oncology/American Society of Clinical Oncology Annual Proceedings, and clinicaltrials.gov databases up until December 2021.DiscussionWe described the results of key trials in the neoadjuvant and adjuvant setting, some of the reasons for conflicting study results, and the implications for clinical practice. Relevant biomarkers in the field are discussed, alongside a brief overview of the immune microenvironment in bladder cancer.ConclusionsPerioperative ICIs have shown promising efficacy with low toxicity in the neoadjuvant setting. The two large trials in the adjuvant setting have been contradictory. The efficacy of perioperative ICIs combined with favorable tolerability and better toxicity profile compared with chemotherapy, with the potential for biomarker-driven patient selection, may lead to a change in future practice. There is, however, a lack of long-term survival and toxicity data for those treated with ICIs, and this needs to be developed further to demonstrate an added survival benefit by using ICIs.
| S-EPMC9935774 | biostudies-literature
Project description:Although Muscle Invasive Bladder Cancer (MIBC) is increasing in incidence, treatment has largely remained limited to radical cystectomy with or without cisplatin-based neoadjuvant and/or adjuvant chemotherapy. We reviewed the current and recent clinical trials evaluating perioperative chemotherapy, targeted therapy, and novel therapeutic regimens for MIBC patients undergoing radical cystectomy.An overview of perioperative MIBC management was conducted initially using MEDLINE. The Clinical Trials Registry and MEDLINE were further searched specifically for perioperative MIBC chemotherapy, targeted therapy, and other novel therapeutic approaches. Trials involving non-perioperative management, operative management other than radical cystectomy, multiple tumors, or purely superficial or metastatic disease were excluded from selection. These criteria were not specifically fulfilled for mTOR inhibitor and immune therapy trials. Only phase III chemotherapy and phase II targeted therapy trials found in the Clinical Trials Registry were selected. MEDLINE searches of specific treatments were limited to January 2009 to January 2014 whereas the Clinical Trials Registry search had no timeline. Systematic MEDLINE searches had no phase restrictions. Trials known by the authors to fulfill search criteria but were not found via searches were also selected.Twenty-five trials were selected from the Clinical Trials Registry including 7 phase III chemotherapy trials, 11 Phase II targeted therapy trials, 3 immune therapy trials, 1 mammalian target of rapamycin (mTOR) inhibitor trial, and 3 gene and vaccine therapy trials. Nine trials have been completed and 5 have been terminated early or withdrawn. Nine trials have data available when individually searched using MEDLINE and/or Google. Systematic searches of MEDLINE separately found 12 trials in the past 5 years. Two phase III chemotherapy trials were selected based on knowledge by the authors. No phase III trials of targeted therapy have been registered or published.New trials are currently being conducted that may revolutionize MIBC treatment preceding or following cystectomy. Head-to-head phase III trials of perioperative chemotherapy and further phase II and phase III trials of targeted therapy and other therapeutic approaches are necessary before the current cisplatin-based perioperative chemotherapy paradigm is altered.
| S-EPMC4301463 | biostudies-literature
Project description:BackgroundIdentifying optimal chemotherapy (CT) utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of perioperative CT for muscle-invasive bladder cancer (MIBC).MethodsThe Ontario Cancer Registry and linked treated records were used to identify neoadjuvant and adjuvant CT rates among patients with MIBC during 2004-2013. Monte Carlo simulation was used to estimate the proportion of observed rate variation that could be due to chance alone. The criterion-based benchmarking approach was used to explore whether social and health-system factors were associated with CT rates. We also used the "pared-mean" approach to identify a benchmark population of hospitals with the highest treatment rates. Hospital CT rates were adjusted for case mix and simulated using a multi-level multivariable model and a parametric bootstrapping approach.ResultsThe study population included 2581 patients; perioperative CT was delivered to 31% (798/2581). Multivariate analysis showed that treatment was strongly associated with patient socioeconomic status and hospital teaching status. The benchmark rate was 36%. Unadjusted CT rates were significantly different across hospitals (range 0%-52%, P < .001). The unadjusted benchmark perioperative CT rate was 45% (95% CI 40%-50%); utilization rate in nonbenchmark hospitals was 28% (95% CI 26%-30%). When using simulated CT rates adjusted for case mix, the benchmark CT rate was 41% (95% CI 35%-47%) and the nonbenchmark hospital CT rate was 30% (95% CI 28%-32%). The simulation analysis suggested that the observed component of variation (38%) was outside the 95% CI (22%-28%) of what could be expected due to chance alone.ConclusionsThere is significant systematic variation in perioperative CT rates for MIBC across hospitals in routine practice. The benchmark perioperative CT rate for MIBC is 36%-41%.
| S-EPMC6797575 | biostudies-literature
Project description:Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved in recent years. Immune checkpoint inhibitors and targeted agents, such as antibody-drug conjugates or FGFR inhibitors, are new therapeutic alternatives and have shown their benefit in advanced disease. Currently, several clinical trials are investigating the role of these drugs, as monotherapy and in combination with chemotherapy, in the neoadjuvant and adjuvant settings with promising outcomes. In addition, the development of predictive biomarkers could predict responses to neoadjuvant therapies.
| S-EPMC9913718 | biostudies-literature
Project description: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.
| S-EPMC8268978 | biostudies-literature
Project description:Purpose: Bladder cancer (BCa) is generally considered one of the most prevalent deadly diseases worldwide. Patients suffering from muscle-invasive bladder cancer (MIBC) possess dismal prognoses, while those with non-muscle-invasive bladder cancer (NMIBC) generally have a favorable outcome after local treatment. However, some NMIBCs relapse and progress to MIBC, with an unclarified mechanism. Hence, insight into the genetic drivers of BCa progression has tremendous potential benefits for precision therapeutics, risk stratification, and molecular diagnosis. Methods: In this study, three cohorts profile datasets (GSE13507, GSE32584, and GSE89) consisting of NMIBC and MIBC samples were integrated to address the differently expressed genes (DEGs). Subsequently, the protein-protein interaction (PPI) network and pathway enrichment analysis of DGEs were performed. Results: Six collagen members (COL1A1, COL1A2, COL5A2, COL6A1, COL6A2, and COL6A3) were up-regulated and gathered in the ECM-receptor interaction signal pathway identified by KEGG pathway analysis and GSEA. Evidence derived from the Oncomine and TCGA databases indicated that the 6 collagen genes promote the progression of BCa and are negatively associated with patient prognosis. Moreover, taking COL1A1 as a further research object, the results showed that COL1A1 was up-regulated in MIBC and its knockdown significantly inhibited the proliferation, migration, and invasion of 5637 and T24 cells by inhibiting epithelial-mesenchymal transition (EMT) process and the TGF-β signaling pathway. Conclusion: With integrated bioinformatic analysis and cell experiments, we showed that 6 collagen family members are high progression risk factors and that they can be used as independent effective diagnostic and prognostic biomarkers for BCa.
| S-EPMC6511250 | biostudies-literature