scholarly journals Bladder Cancer Tissue-Based Biomarkers

2021 ◽  
Vol 2 (1) ◽  
pp. 53-71
Author(s):  
Francesco Soria ◽  
Marta Sanchez-Carbayo ◽  
Natalya Benderska-Söder ◽  
Bernd J Schmidz-Dräger ◽  
Stefania Zamboni ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Systemic Chemotherapy ◽  
Disease Recurrence ◽  
Invasive Disease ◽  
Cancer Tissue ◽  
Fgfr3 Mutation ◽  
Tumor Mutational Burden ◽  
Bladder Cancer Tissue ◽  
Predictive Role ◽  
Muscle Invasive

This review aims to provide a practical update regarding the current role of tissue-based biomarkers in bladder cancer. Their prognostic and predictive role both in non-muscle-invasive (NMIBC) and in muscle-invasive disease (MIBC) has been reviewed with particular focus to their use in clinical practice. In summary, the literature on the prediction of disease recurrence in NMIBC is inconclusive, and there is little information on prediction of response to intravesical bacillus Calmette-Guerin (BCG). Concerning disease progression, external prospective validation studies suggest that FGFR3 mutation status and gene signatures may improve models that are based only on clinicopathologic information. In MIBC, tissue-based biomarkers are increasingly important, since they may predict the response to systemic chemotherapy and immunotherapy. In particular, the advent of molecular characterization promises to revolutionize the paradigm of decision-making in the treatment of MIBC. Molecular subtyping has been shown to improve the prediction of pathological stage at RC and to predict the response to systemic chemotherapy and immunotherapy. However, external and prospective validations are warranted to confirm these preliminary findings. Several different tissue-based biomarkers such as PD-1/PD-L1 expression, tumor mutational burden, and the analysis of tumor microenvironment, may in future play a role in selecting patients for systemic immunotherapy. However, to date, no pretreatment recommendations can be definitively made on the basis of any molecular predictors. In conclusion, despite the potential of tissue-based biomarkers, their use in bladder cancer should be limited to experimental settings.

Development of a novel immunotherapy for muscle invasive bladder cancer (MIBC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 402-402
Author(s):  
Irina Y. Tcherepanova ◽  
Bradley C. Leibovich ◽  
Jacoba Slagter-Jager ◽  
Patrick Dillon ◽  
Shawn Michael Leland ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Rna Extraction ◽  
Rna Degradation ◽  
Invasive Bladder Cancer ◽  
Cancer Tissue ◽  
Autologous Tumor ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Tissue ◽  
Bladder Cancer Tissue ◽  
Muscle Invasive

402 Background: AGS-003 is an autologous tumor RNA-loaded dendritic cell-based immunotherapy being tested in advanced renal cell carcinoma (RCC) patients. The immunologic specificity for the patient’s own tumor is achieved using amplified tumor RNA electroporated into monocyte derived dendritic cells. To produce AGS-003 for RCC patients the RNA is amplified from a 100 mg primary tumor sample obtained via nephrectomy. In this non treatment study we evaluated the feasibility of RNA amplification from MIBC tissue acquired by transurethral resection of bladder tumor (TURBT). Methods: MIBC tissue was obtained via TURBT. Following draining of the irrigant used during the TURBT procedure, tissue was placed into an RNA preservative solution to prevent RNA degradation until processing. Methods developed for the amplification of RCC tumor RNA and RNA quality testing were applied to the RNA extracted from the MIBC specimens. Results: This work demonstrated that the methods developed for the amplification and testing of RNA from RCC can be successfully employed for the amplification of RNA from MIBC specimens collected by TURBT. Results demonstrated that the total RNA yields obtained from bladder tissue exceed that of similar masses of primary RCC tumors. This finding enabled the reduction in the amount of starting material from 100 mg to 50 mg of bladder tissue. The amount of amplified RNA produced from the lower bladder cancer masses were sufficient to support the production of immunotherapy at full scale (17 doses average). Conclusions: These data demonstrate the feasibility of RNA extraction and amplification from muscle invasive bladder cancer tissue and supports our planned phase II clinical study. [Table: see text]

Treatment patterns in patients with recurrent high-risk bladder cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 303-303
Author(s):  
Eric Christian Ballon-Landa ◽  
Karim Chamie ◽  
Jeffrey C. Bassett ◽  
Timothy J. Daskivich ◽  
Julie Lai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Radical Cystectomy ◽  
Systemic Chemotherapy ◽  
Invasive Disease ◽  
P Value ◽  
High Grade ◽  
Aggressive Treatment ◽  
Curative Intent ◽  
Muscle Invasive

303 Background: Patients with high-risk bladder cancer are apt to develop multiple recurrences. Since the association of recurrences with aggressive treatment in individuals with recurrent high-grade disease has not been quantified, we sought to determine whether increasing number of recurrences correlates with higher treatment rates. Methods: Using linked SEER-Medicare data, we identified subjects with recurrent high-grade, non-muscle-invasive disease diagnosed in 1992–2002 and followed until 2007. Using propensity score and competing-risks regression analyses, we quantified the incidence of radical cystectomy, radiotherapy, and systemic chemotherapy after each recurrence. We further restricted our analyses of treatment in auspicious environments, defined as those patients most suited for aggressive intervention: age <70, Charlson 0, and undifferentiated T1 tumors treated at academic cancer centers. Results: Of 4,521 subjects, (59.6%) 2,694 recurred more than once within two years of diagnosis. Compared with patients who only had one recurrence, those with ≥4 recurrences were less likely to undergo radical cystectomy (9.7% vs 12.1%, p value=0.03), but more likely to undergo radiotherapy (18.0% vs 12.1%, p value<0.01) and systemic chemotherapy (6.7% vs 4.2%, p value<0.01). For patients with ≥4 recurrences, only 25% were treated with curative intent, while 43% were similarly treated in auspicious environments. Conclusions: Only 25% of patients with high-risk bladder cancer who recur ≥4 times undergo treatment for curative intent. Increasing recurrences do not appear to alter the treatment course, as patients and their doctors may be unable or unwilling to proceed with aggressive treatment despite mounting risk of disease progression. [Table: see text]

Discovering Therapeutic Protein Targets for Bladder Cancer Using Proteomic Data Analysis

2020 ◽  
Vol 13 (2) ◽  
pp. 150-172 ◽  
Author(s):  
Samira Bahrami ◽  
Bahram Kazemi ◽  
Hakimeh Zali ◽  
Peter C. Black ◽  
Abbas Basiri ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gene Ontology ◽  
Monoclonal Antibodies ◽  
Membrane Proteins ◽  
Growth Factor Receptor ◽  
Subcellular Location ◽  
Cancer Tissue ◽  
Heat Shock Protein 60 ◽  
Absolute Quantitation ◽  
Muscle Invasive

Background: Bladder cancer accounts for almost 54% of urinary system cancer and is the second most frequent cause of death in genitourinary malignancies after prostate cancer. About 70% of bladder tumors are non-muscle-invasive, and the rest are muscle-invasive. Recurrence of the tumor is the common feature of bladder cancer. Chemotherapy is a conventional treatment for MIBC, but it cannot improve the survival rate of these patients sufficiently. Therefore, researchers must develop new therapies. Antibody-based therapy is one of the most important strategies for the treatment of solid tumors. Selecting a suitable target is the most critical step for this strategy. Objective: The aim of this study is to detect therapeutic cell surface antigen targets in bladder cancer using data obtained by proteomic studies. Methods: Isobaric tag for relative and absolute quantitation (iTRAQ) analysis had identified 131 overexpressed proteins in baldder cancer tissue and reverse-phase proteomic array (RPPA) analysis had been done for 343 tumor tissues and 208 antibodies. All identified proteins from two studies (131+208 proteins) were collected and duplicates were removed (331 unique proteins). Gene ontology study was performed using gene ontology (GO) and protein analysis through evolutionary relationships (PANTHER) databases. The Human Protein Atlas database was used to search the protein class and subcellular location of membrane proteins obtained from the PANTHER analysis. Results: Membrane proteins that could be suitable therapeutic targets for bladder cancer were selected. These included: Epidermal growth factor receptor (EGFR), Her2, Kinase insert domain receptor (KDR), Heat shock protein 60 (HSP60), HSP90, Transferrin receptor (TFRC), Activin A Receptor Like Type 1 (ACVRL1), and cadherin 2 (CDH2). Monoclonal antibodies against these proteins or their inhibitors were used for the treatment of different cancers in preclinical and clinical trials. Conclusion: These monoclonal antibodies and inhibitor molecules and also their combination can be used for the treatment of bladder cancer.

SERS spectroscopy to discriminate between bladder cancer tissue and urothelium

2021 ◽  
Vol 79 ◽  
pp. S1017-S1018
Author(s):  
G. Platkevicius ◽  
E. Zacharovas ◽  
M. Velicka ◽  
A. Čekauskas ◽  
A. Želvys ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Tissue ◽  
Bladder Cancer Tissue

Integrated clinicopathologic and molecular risk stratification for disease recurrence in muscle-invasive bladder cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 490-490
Author(s):  
Ruben Carmona ◽  
Alan Pollack ◽  
Zachary L Smith ◽  
Jeff M. Michalski ◽  
Hiram Alberto Gay ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Molecular Subtype ◽  
Disease Recurrence ◽  
Invasive Bladder Cancer ◽  
Training Set ◽  
Combined Model ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Testing Set

490 Background: Integrating molecular subtypes, gene transcripts associated with disease recurrence (DR), and clinicopathologic features may help risk stratify muscle-invasive bladder cancer (MIBC) patients & guide therapy selection. We hypothesized that combined transcriptomic & clinical data would improve risk stratification for DR (local or distant) after cystectomy +/- adjuvant chemotherapy. Methods: We identified 401 MIBC patients (pT2-4 N0-N3 M0) in The Cancer Genome Atlas with detailed demographic, clinical, pathologic, and treatment-related data. We split the data into training (60%) & testing (40%) sets. We produced RNA gene expression scores for molecular subtype using 48 established, relevant genes (PMID 28988769). In the training set, we performed feature selection by conducting random forest modeling of an additional 108 genes associated with DR. We kept genes of highest importance based on the evaluation of increasing mean-squared error & node purity. We excluded highly correlated genes & used the false discovery rate method for multiple hypotheses testing. We performed univariable analyses on genes of highest importance, molecular subtype, & clinicopathologic variables. Using adjusted multivariable analyses (MVA), we built two models: with & without transcriptomic data. Using the testing set, we compared the final models' performance to predict DR, using receiver operating characteristics & area under the curve (AUC). Results: Median follow-up was 18 months (range 1-168). 104 patients recurred with a 5-yr cumulative incidence of 34.6%[28.6-40.5%]. Using the training set, we identified 6 genes significantly associated with DR (VEGFA, TRMT1, FGFR2B, ERBB2, MMP14, PDGFC). The final MVA showed that the new 6-gene signature (HR 1.61, 95% CI 1.27-2.05, p < 0.001); immune molecular subtype [increased expression of PD-L1, PD-1, IDO1, CXCL11, L1CAM, SAA1] (HR 0.52, 95% CI 0.29-0.94, p = 0.03); smoking status (HR 1.17 per 10 pack-years, 95% CI 1.05-1.29, p = 0.005); and local failure risk factors [≥pT3 with negative margins & ≥10 nodes removed (HR 1.63, 95% CI 1.15-2.32, p = 0.006); ≥pT3 and positive margins OR < 10 nodes removed (HR 3.26, 95%CI 2.43 to 4.09, p = 0.007)], were all significantly associated with DR. This combined model outperformed a stand-alone clinicopathologic model (AUC 0.75 vs. 0.66) in the testing set. The combined model stratified patients based on DR risk into 3 groups with 5-yr cumulative incidences of 19.8%[7.7-31.9%] (low-risk); 34.5%[26.1-42.8%] (intermediate); and 49.8%[37.7-61.9%] (high), Gray’s Test p < 0.0001. Conclusions: To our knowledge, this study is the first to integrate clinicopathologic & transcriptomic information (including molecular subtype) to better stratify MIBC patients by risk of recurrence. This stratification may help guide decision-making for adjuvant treatment. Further validation is warranted.

Efficacy of chemohyperthermia (HIVEC) in patients with high-risk nonmuscle invasive bladder cancer (NMIBC) who fail BCG therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 456-456
Author(s):  
Geraldine Pignot ◽  
Laure Doisy ◽  
Jochen Walz ◽  
Thibault Marquette ◽  
Thomas Maubon ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Invasive Disease ◽  
Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Bcg Therapy ◽  
Risk Of Progression ◽  
Muscle Invasive ◽  
Preservation Rate ◽  
Very High

456 Background: To evaluate Hyperthermic Intra-Vesical Chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (DFS) rate and bladder preservation rate in patients with high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who fail BCG therapy or are contraindicated to BCG. Methods: Between June 2016 and October 2019, patients treated with HIVEC for high-risk NMIBC who failed BCG (Fail-BCG) or BCG-naive if BCG contraindicated (N-BCG) have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. Results: Fifty-three patients, median age 72 [39-93] years, were included (n = 29 Fail-BCG and n = 24 N-BCG). The median follow-up was 18 months. The bladder preservation rate was 92.4%. The RFS rate at 12 months was 60.5%. The RFS rate at 12 months for N-BCG and Fail-BCG groups was respectively 70% and 52.2%. Three patients progressed to muscle-invasive disease, all in the Fail-BCG group and all in the very high-risk EORTC group. Two of them experienced metastatic progression and died from bladder cancer. Conclusions: Chemohyperthermia using HIVEC device achieved a RFS rate of 60% at 1 year and enabled a bladder preservation rate of 92%. Given the low risk of progression in the N-BCG group, HIVEC could be a good alternative. Conversely, for patients with very high-risk tumors that fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression to muscle-invasive disease.

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 Predictors of Outcome of Non–Muscle-Invasive and Muscle-Invasive Bladder Cancer

2011 ◽  
Vol 11 ◽  
pp. 369-381 ◽  
Author(s):  
Ramy F. Youssef ◽  
Yair Lotan
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Predictive Accuracy ◽  
Staging System ◽  
Tumor Grade ◽  
Invasive Disease ◽  
Tnm Staging ◽  
High Rate ◽  
Recurrence Rates ◽  
Muscle Invasive

Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non–muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10–30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non–muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinomain situare the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

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