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Neoadjuvant immunotherapy for muscle invasive urothelial bladder carcinoma: will it change current standards?

ABSTRACT: Immunotherapy, in the form of immune checkpoint inhibitors (ICI), has shown activity in metastatic urothelial bladder carcinoma, resulting in the approval of several ICI agents in the first- and second-line settings. This has led to an increased interest in studying their efficacy in the neoadjuvant setting for muscle invasive disease - an area of significant unmet need. This non-systematic review will look at the evidence supporting the use of ICI in the neoadjuvant setting for this tumor, results of early-phase studies, ongoing trials, and possible future applications for these drugs.

SUBMITTER: Renner A

PROVIDER: S-EPMC8273398 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Neoadjuvant immunotherapy for muscle invasive urothelial bladder carcinoma: will it change current standards?

Renner Alex A Burotto Mauricio M Valdes Jose Miguel JM Roman Juan Carlos JC Walton-Diaz Annerleim A

Therapeutic advances in urology 20210101

Immunotherapy, in the form of immune checkpoint inhibitors (ICI), has shown activity in metastatic urothelial bladder carcinoma, resulting in the approval of several ICI agents in the first- and second-line settings. This has led to an increased interest in studying their efficacy in the neoadjuvant setting for muscle invasive disease - an area of significant unmet need. This non-systematic review will look at the evidence supporting the use of ICI in the neoadjuvant setting for this tumor, resu ...[more]

PMID: 34290827

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Project description:Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.

Project description:PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA-IVB, who had received maximal transurethral resection of bladder tumor (TURBT) followed by CCRT from the Taiwan Cancer Registry Database. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on the preexisting COPD status (within 1 year before CCRT) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD). RESULTS: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality in Group 2 compared with Group 1 was 1.89 (1.12-3.18), p = 0.017. The aHRs (95% CIs) of all-cause mortality for ≥1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT for bladder preservation were 3.26 (1.95-5.46) and 6.33 (3.55-11.281) compared with non-COPDAE patients with MIBUC undergoing CCRT for bladder preservation. CONCLUSIONS: Among patients with MIBUC undergoing TURBT followed by CCRT for bladder preservation, current smokers with smoking-related COPD had worse survival outcomes than did nonsmokers without COPD. CONDENSED ABSTRACT: This was the first study to estimate the survival impact of smoking-related chronic obstructive pulmonary disease (COPD) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy (CCRT) for bladder preservation. Smoking-related COPD was a significant independent risk factor for all-cause mortality in patients with clinical stages IIA-IVB receiving TURBT followed by CCRT. Hospitalization frequency for COPD with at least one acute exacerbation within 1 year before CCRT was highly associated with high mortality for patients with MIBUC receiving CCRT for bladder preservation. Not only all-cause death but also bladder cancer death and COPD death were significantly higher in the current-smoking COPD group than in the never-smoking non-COPD group.

Dataset Information

Neoadjuvant immunotherapy for muscle invasive urothelial bladder carcinoma: will it change current standards?

Publications

Neoadjuvant immunotherapy for muscle invasive urothelial bladder carcinoma: will it change current standards?

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