Stromal LAG-3+cells infiltration defines poor prognosis subtype muscle-invasive bladder cancer with immunoevasive contexture

BackgroundLymphocyte activation gene 3 (LAG-3) is a promising immune checkpoint therapeutic target being evaluated in clinical trials. We assessed the LAG-3+cells distribution, its association with clinical outcomes and immune contexture and its role in the landscape of muscle-invasive bladder cancer (MIBC) treatment.Methods141 patients with MIBC from Zhongshan Hospital were included for survival and adjuvant chemotherapy (ACT) benefit analyses. 32 fresh resected samples of MIBC were collected to detect CD8+T cells functional state. The molecular classification analyses were based on 391 patients with MIBC from The Cancer Genome Atlas. Immunohistochemistry and flow cytometry were performed to characterize various immune cells infiltration.ResultsIn Kaplan-Meier analyses and Cox regression models, stromal LAG-3+cells enrichment was consistently associated with inferior overall survival and disease-free survival, and indicated suboptimal responsiveness to ACT. Patents with high stromal LAG-3+cells possessed increased protumor cells, immunosuppressive cytokines and immune checkpoint expression. The phenotypic analyses of CD8+T cells correlated its dysfunctional state with LAG-3+cells. Besides, LAG-3 mRNA level was linked to luminal and basal subtypes of MIBC. LAG-3-high tumors exhibited limited FGFR3 mutation and signaling signature, and displayed activated immunotherapeutic and EGFR-associated pathway.ConclusionsStromal LAG-3+cells abundance indicated an immunoevasive contexture with dysfunctional CD8+T cells, and represented an independent predictor for adverse survival outcome and ACT resistance in MIBC. LAG-3 expression could potentially be a novel biomarker for FGFR3-targeted and EGFR-targeted therapies and immunotherapy. The crucial role of LAG-3+cells in the therapeutic landscape of MIBC needs further validation retrospectively and prospectively.

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Using radiologic response to predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.361 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 361-361

Author(s):

Shingo Hatakeyama ◽

Hayato Yamamoto ◽

Akiko Okamoto ◽

Atsushi Imai ◽

Takahiro Yoneyama ◽

...

Keyword(s):

Bladder Cancer ◽

Multivariate Analysis ◽

Neoadjuvant Chemotherapy ◽

Radical Cystectomy ◽

Cox Regression ◽

Disease Free Survival ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Contrast Enhanced Ct ◽

Muscle Invasive

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to <pT2 was 37 (49%) in responders, 5 (13%) in non-responders group. Radiologic response was a strong predictor of DFS and OS. A 5-year advantages of DFS and OS in responders vs. non-responders were 88% and 86% vs. 64% and 69%, respectively (P=0.021 and P=0.013). Multivariate analysis showed radiologic response was the independent factor for DFS and OS. Conclusions: Radiological response post carboplatin-based neoadjuvant chemotherapy is associated with OS in patients with MIBC.

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Construction and Validation of a Novel Eight-Gene Risk Score to Predict the Malignant Progression and Prognoses in Bladder Cancer Patients

10.21203/rs.3.rs-120263/v1 ◽

2020 ◽

Author(s):

Ruiliang Wang ◽

Zongtai Zheng ◽

Shiyu Mao ◽

Wentao Zhang ◽

Ji Liu ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Score ◽

Cox Regression ◽

Cox Model ◽

Malignant Progression ◽

The Cancer Genome Atlas ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Normal Bladder ◽

Muscle Invasive

Abstract The progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) largely predisposes a life-threatening risk. Owing to this, it is of paramount importance to find new relevant molecular models that will allow for effectively predict the malignant progression of BC. Based on the RNA-Sequence data of 49 BC patients in our center and weighted gene co-expression network analysis methods, a co-expression network was developed using these genes before selecting the three key modules. Univariate Cox regression was used to select the key module genes with prognostic value in The Cancer Genome Atlas Program (TCGA). Subsequently, we developed an eight-gene risk score using the Least absolute shrinkage and selection operator Cox model. Notably, the eight-gene risk score was observed to be closely related to the malignant clinical features and also showed a favorable predictive power of differentiation between NMIBC and MIBC in the training (TCGA) and the two validation sets (GSE3289 and GSE13507). Furthermore, we generated a nomogram for predicting the overall survival. Both the calibrations and decision curve analysis curves displayed predictive effectiveness of the nomogram. Lastly, the RT-qPCR results revealed that the majority of the eight genes were differentially expressed between BC cell lines and a normal bladder epithelial cell line. Hence, from our study, we established a model of eight-gene risk score, with the potential of predicting malignant progression and determine prognoses of BC patients.

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Construction and validation of a novel eight-gene risk score to predict the progression and prognosis of bladder cancer

10.21203/rs.3.rs-120263/v2 ◽

2021 ◽

Author(s):

Ruiliang Wang ◽

Zongtai Zheng ◽

Shiyu Mao ◽

Wentao Zhang ◽

Ji Liu ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Score ◽

Cox Regression ◽

Cox Model ◽

The Cancer Genome Atlas ◽

Invasive Bladder Cancer ◽

Training Dataset ◽

Muscle Invasive Bladder Cancer ◽

Risk Of Death ◽

Muscle Invasive

Abstract Background: The progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) increases the risk of death. It is therefore important to find new relevant molecular models that will allow for effective prediction of the progression of bladder cancer (BC).Methods: Using RNA-Sequence data of 49 BC patients in our center and weighted gene co-expression network analysis methods, a co-expression network of genes was developed from which three key modules with prognostic value were selected using Univariate Cox regression in The Cancer Genome Atlas Program (TCGA). Subsequently, an eight-gene risk score was established using the Least absolute shrinkage and selection operator Cox model. Results: A novel eight-gene risk score was closely related to the malignant clinical features of BC and could predict the prognosis of patients in the training dataset (TCGA) and two validation sets (GSE3289 and GSE13507). Further, a nomogram for predicting the overall survival of patients was designed. The nomogram showed good calibration with clinical value through decision curve analysis. Lastly, we found that the mRNA and protein expression level of the eight genes were found to be differentially expressed in cell lines and tissue.Conclusions: In our study, we established a novel eight-gene risk score which could predict the progression and prognoses of BC patients.

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FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

Journal of Clinical Medicine ◽

10.3390/jcm9040994 ◽

2020 ◽

Vol 9 (4) ◽

pp. 994 ◽

Cited By ~ 2

Author(s):

Danijel Sikic ◽

Markus Eckstein ◽

Ralph M. Wirtz ◽

Jonas Jarczyk ◽

Thomas S. Worst ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Multivariable Analysis ◽

Disease Free Survival ◽

Gene Panel ◽

The Cancer Genome Atlas ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Free Survival ◽

Muscle Invasive

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

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Identification of a Nuclear Mitochondrial-Related Multi-Genes Signature to Predict the Prognosis of Bladder Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.746029 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xuewen Jiang ◽

Yangyang Xia ◽

Hui Meng ◽

Yaxiao Liu ◽

Jianfeng Cui ◽

...

Keyword(s):

Bladder Cancer ◽

Cox Regression ◽

Checkpoint Inhibitors ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Genome Database ◽

Cox Regression Analysis ◽

Muscle Invasive

IntroductionBladder cancer (BC) is one of the most prevalent urinary cancers, and its management is still a problem causing recurrence and progression, elevating mortality.Materials and MethodsWe aimed at the nuclear mitochondria-related genes (MTRGs), collected from the MITOMAP: A Human Mitochondrial Genome Database. Meanwhile, the expression profiles and clinical information of BC were downloaded from the Cancer Genome Atlas (TCGA) as a training group. The univariate, multivariate, and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a nuclear mitochondrial-related multi-genes signature and the prognostic nomogram.ResultsA total of 17 nuclear MTRGs were identified to be correlated with the overall survival (OS) of BC patients, and a nuclear MTRGs signature based on 16 genes expression was further determined by the LASSO Cox regression analysis. Based on a nuclear MTRGs scoring system, BC patients from the TCGA cohort were divided into high- and low- nuclear MTRGs score groups. Patients with a high nuclear MTRGs score exhibited a significantly poorer outcome (median OS: 92.90 vs 20.20 months, p<0.0001). The nuclear MTRGs signature was further verified in three independent datasets, namely, GSE13507, GSE31684, and GSE32548, from the Gene Expression Omnibus (GEO). The BC patients with a high nuclear MTRGs score had significantly worse survival (median OS in GSE13507: 31.52 vs 98.00 months, p<0.05; GSE31684: 32.85 months vs unreached, p<0.05; GSE32548: unreached vs unreached, p<0.05). Furthermore, muscle-invasive bladder cancer (MIBC) patients had a significantly higher nuclear MTRGs score (p<0.05) than non-muscle-invasive bladder cancer (NMIBC) patients. The integrated signature outperformed each involved MTRG. In addition, a nuclear MTRGs-based nomogram was constructed as a novel prediction prognosis model, whose AUC values for OS at 1, 3, 5 years were 0.76, 0.75, and 0.75, respectively, showing the prognostic nomogram had good and stable predicting ability. Enrichment analyses of the hallmark gene set and KEGG pathway revealed that the E2F targets, G2M checkpoint pathways, and cell cycle had influences on the survival of BC patients. Furthermore, the analysis of tumor microenvironment indicated more CD8+ T cells and higher immune score in patients with high nuclear MTRGs score, which might confer sensitivity to immune checkpoint inhibitors.ConclusionsNot only could the signature and prognostic nomogram predict the prognosis of BC, but it also had potential therapeutic guidance.

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Neoadjuvant gemcitabine and carboplatin followed by immediate radical cystectomy for muscle-invasive bladder cancer patients ineligible for cisplatin-based chemotherapy: A propensity score-matched analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.375 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 375-375

Author(s):

Takuya Koie ◽

Chikara Ohyama ◽

Atsushi Imai ◽

Shingo Hatakeyama ◽

Takahiro Yoneyama ◽

...

Keyword(s):

Bladder Cancer ◽

Propensity Score ◽

Cox Regression ◽

Propensity Score Analysis ◽

Strong Predictor ◽

Disease Free Survival ◽

Invasive Bladder Cancer ◽

Rank Test ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

375 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin (CDDP)-based chemotherapy. We conducted a propensity score analysis to evaluate the clinical significance of neoadjuvant gemcitabine and carboplatin (GCarbo) chemotherapy for CDDP-ineligible patients with MIBC. Methods: We enrolled 381 patients with MIBC, and retrospectively compared two cohorts of CDDP-ineligible patients with MIBC. The GCarbo cohort consisted of 63 patients, who received 2 courses of GCarbo consisting of 800 mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin with an area under the curve of 4 on day 2, prior to RC. The RC alone cohort consisted of 56 patients receiving RC without neoadjuvant or adjuvant chemotherapy. The endpoints were overall (OS), cancer-specific (CSS), and disease-free survival (DFS). The oncological outcomes were analyzed using log-rank test and multivariate Cox regression model. Results: Propensity score-matched analysis indicated 56 matched pairs from both groups. The 3-year OS rates were 77.9% for the GCarbo cohort and 50.7% for the RC alone cohort (P = 0.002). The 3-year CSS rates were 92.8% for the GCarbo cohort and 52.6% for RC alone group (P < 0.001). The 3-year DFS rates were 80.6% for the GCarbo cohort and 48.1% for the RC alone cohort (P = 0.005). Multivariate analysis revealed that GCarbo was an extremely strong predictor of improved survival. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC significantly improved OS, CSS, and DFS in CDDP-ineligible MIBC patients.

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PD-L1/PD-1 expression as a predictor of response to BCG in patients with high-risk non–muscle invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4550 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4550-4550

Author(s):

Mathieu Roumiguie ◽

Eva Comperat ◽

Yann Neuzillet ◽

Francois-Xavier Nouhaud ◽

Vivien Graffeille ◽

...

Keyword(s):

Bladder Cancer ◽

T Cells ◽

High Risk ◽

Univariate Analysis ◽

Disease Free Survival ◽

Tumour Cells ◽

Invasive Bladder Cancer ◽

Pharmacological Intervention ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

4550 Background: Intravesical BCG instillation (IBI) is the gold standard adjuvant treatment after transurethral resection of the bladder in high risk non muscle invasive bladder cancer (HR-NMIBC). IBI induce a type of Th1 immune response requiring a recruitment of cytotoxic cells. This response is downregulated by the PD-1/PD-L1 checkpoint inhibitors through an inhibition of the action of CD8+ T cells against their target. Our purpose was to assess whether PD-1/PD-L1 expression was associated with IBI response in HR-NMIBC. Methods: Histologically confirmed HR-NMBC from 5 academic French institutions which underwent maintenance IBI were retrospectively included. The following data were collected: pathological stage, grade, concomitant carcinoma in situ, number of lesions and size. From a paraffin embedded samples of initial resection, a unique dedicated uropathologist quantified immunochemistry expression of CD3, CD8, PD-L1 (antibody SP263/ SP142, E1L3N, 28 8) in both tumour cells and tumoral microenvironment. Univariate and multivariate analyses were performed using Cox proportional hazards model. Results: Overall 140 patients (median age 66.5 years, range:35-87; sex ratio male vs female:6:1) were included. The distribution of NMIBC tumour for stage and grade was: Ta 37.2% (n = 52), T1 62.8% (n = 88) and high grade 100% (n = 140) respectively. The median number of IBI which were delivered was 12 (range 7-36). The median length of follow-up was 54.24 mo (95% CI = 49.91-58.68). Overall, 25 patients (17.9%) had a recurrence/or progression. The 72mo Disease free survival (DFS) rate was 81.11% (95% CI = 72.20-87.41). Using univariate analysis, we found that Age (HR = 1.07; [1.02-1.12] p = 0.005), CD3/CD8 ratio (HR per 10 units = 3.43 [1.62-7.23] p = 0.014) and PD-L1(HR per 10 units = 1.65 [1.15-2.38] p = 0.046) were associated with DFS. In multivariate analysis, Age (HR = 1.07 [1.02-1.13] p = 0.009), CD3/CD8 ratio (HR per 10 units = 1.96 [1.28-3.00] p = 0.02) and PD-L1 expression in tumour cells (HR per 10 units = 3.38 [1.61-7.11] p = 0.01) remained significantly associated with DFS. Conclusions: PD-L1 expression in tumour cells and the T cells population in tumour microenvironment were both predictive factors of BCG response in HR-NMIBC. These results build a scientific rationale for pharmacological intervention on a molecular target using immuno-oncology.

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Sexual dimorphism in outcomes of non-muscle invasive bladder cancer: a role of CD163+ M2 macrophages, B cells and PD-L1 immune checkpoint

10.1101/2021.01.23.427909 ◽

2021 ◽

Author(s):

Stephen Chenard ◽

Chelsea Jackson ◽

Thiago Vidotto ◽

Lina Chen ◽

Céline Hardy ◽

...

Keyword(s):

Bladder Cancer ◽

T Cells ◽

Sexual Dimorphism ◽

B Cells ◽

Immune Checkpoint ◽

Cell Types ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Female Patients ◽

Muscle Invasive

AbstractNon-muscle invasive bladder cancer (NMIBC) is significantly more common in men than women. However, female patients with NMIBC often present with more aggressive disease and do not respond as well to immunotherapy treatments. We hypothesized that sexual dimorphism in the tumor immune microenvironment (TIME) may contribute to the inferior clinical outcomes observed in female patients. To test this hypothesis, we interrogated the expression patterns of genes associated with specific immune cell types and immune regulatory pathways using tumor whole transcriptome profiles from male (n=357) and female (n=103) patients with NMIBC. High-grade tumors from female patients exhibited significantly increased expression of CD40, CTLA4, PDCD1, LAG3 and ICOS immune checkpoint genes. Based on the significant differences in expression profiles of these genes and the cell types that most commonly express these in the TIME, we evaluated the density and spatial distribution of CD8+Ki67+ (activated cytotoxic T cells), FoxP3+ (regulatory T cells), CD103+ (tissue resident T cells), CD163+ (M2-like tumor associated macrophages), CD79a+ (B cells), PD-L1+ (Programmed-Death Ligand-1) and PD-1+ cells using multiplexed immunofluorescence in an independent cohort of 332 patient tumors on a tissue microarray (n=259 males and n=73 females). Tumors from female patients showed significantly higher infiltration of CD163+ macrophages and PD-L1+ cells compared to tumors from male patients. Notably, increased infiltration of CD163+ macrophages and CD79a+ B cells independently associated with decreased recurrence free survival. Not only do these results have the potential to inform the rational utilization of immunomodulatory therapies based on the TIME of both male and female patients with NMIBC, these novel findings highlight the necessity of considering sexual dimorphism in the design of future immunotherapy trials.

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Rapamycin enhances BCG-specific γδ T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001941 ◽

2021 ◽

Vol 9 (3) ◽

pp. e001941

Author(s):

Niannian Ji ◽

Neelam Mukherjee ◽

Ryan M Reyes ◽

Jonathan Gelfond ◽

Martin Javors ◽

...

Keyword(s):

Bladder Cancer ◽

T Cells ◽

Γδ T Cells ◽

Percentage Change ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Double Blind ◽

Bcg Therapy ◽

Intravesical Bcg ◽

Muscle Invasive

BackgroundAlthough intravesical BCG is the standard treatment of high-grade non-muscle invasive bladder cancer (NMIBC), response rates remain unsatisfactory. In preclinical models, rapamycin enhances BCG vaccine efficacy against tuberculosis and the killing capacity of γδ T cells, which are critical for BCG’s antitumor effects. Here, we monitored immunity, safety, and tolerability of rapamycin combined with BCG in patients with NMIBC.MethodsA randomized double-blind trial of oral rapamycin (0.5 or 2.0 mg daily) versus placebo for 1 month was conducted in patients with NMIBC concurrently receiving 3 weekly BCG instillations (NCT02753309). The primary outcome was induction of BCG-specific γδ T cells, measured as a percentage change from baseline. Post-BCG urinary cytokines and immune cells were examined as surrogates for local immune response in the bladder. Secondary outcomes measured were adverse events (AEs) and tolerability using validated patient-reported questionnaires.ResultsThirty-one patients were randomized (11 placebo, 8 rapamycin 2.0 mg, and 12 rapamycin 0.5 mg). AEs were similar across groups and most were grade 1–2. One (12.5%) patient randomized to 2.0 mg rapamycin was taken off treatment due to stomatitis. No significant differences in urinary symptoms, bowel function, or bother were observed between groups. The median (IQR) percentage change in BCG-specific γδ T cells from baseline per group was as follows: −26% (−51% to 24%) for placebo, 9.6% (−59% to 117%) for rapamycin 0.5 mg (versus placebo, p=0.18), and 78.8% (−31% to 115%) for rapamycin 2.0 mg (versus placebo, p=0.03). BCG-induced cytokines showed a progressive increase in IL-8 (p=0.02) and TNF-α (p=0.04) over time for patients on rapamycin 2.0 mg, whereas patients receiving placebo had no significant change in urinary cytokines. Compared with placebo, patients receiving 2.0 mg rapamycin had increased urinary γδ T cells at the first week of BCG (p=0.02).ConclusionsFour weeks of 0.5 and 2.0 mg oral rapamycin daily is safe and tolerable in combination with BCG for patients with NMIBC. Rapamycin enhances BCG-specific γδ T cell immunity and boosts urinary cytokines during BCG treatment. Further study is needed to determine long-term rapamycin safety, tolerability and effects on BCG efficacy.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22137201 ◽

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.

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