scholarly journals Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer

2013 ◽  
Vol 3 (6-S4) ◽  
pp. 193 ◽  
Author(s):  
Venu Chalasani ◽  
Joseph L. Chin ◽  
Jonathan I. Izawa
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Urothelial Cancer ◽  
Small Cell ◽  
Urothelial Bladder Cancer ◽  
Divergent Differentiation ◽  
Urothelial Bladder ◽  
Worse Prognosis

Bladder cancer can be classified histologically as urothelial ornon-urothelial. Urothelial cancer has a propensity for divergentdifferentiation, which has increasingly been recognized in recentyears due to heightened awareness and improved immunohistochemistrytechniques. Furthermore, the recent World HealthOrganization classification of urothelial cancers improved clarityon this issue, with its listing of 13 histologic variants of urothelialcancer. The divergent differentiation patterns include, amongstothers, squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelialcancer. Attempts to quantify the amount of divergent differentiationpresent, such as using the nonconventional differentiationnumber, have been made recently, which will improve the abilityto compare publications from different centres. Genetic-basedstudies have indicated that the histologic variants of urothelialcancer arise from a common clonal precursor. Mostly, the currentevidence suggests that urothelial cancer with divergent differentiationhas a worse prognosis when compared with pure urothelialcancer. This article will review the current literature on varianthistologies of urothelial cancer, and well as new developmentsin pure squamous cell carcinoma, small cell carcinoma and adenocarcinomaof the bladder.

scholarly journals Diagnosis and treatment in primary bladder small cell carcinoma: Literature review

2016 ◽  
Vol 88 (1) ◽  
pp. 52 ◽  
Author(s):  
Orcun Celik ◽  
Gokhan Ekin ◽  
Tumay Ipekci ◽  
Salih Budak ◽  
Yusuf Ozlem Ilbey
Keyword(s):  
Bladder Cancer ◽  
Bladder Carcinoma ◽  
Treatment Algorithm ◽  
Small Cell ◽  
Treatment Modalities ◽  
Urothelial Bladder Cancer ◽  
Fatal Disease ◽  
Urothelial Bladder ◽  
Primary Bladder ◽  
Worse Prognosis

Small cell bladder carcinoma is a rare and frequently fatal disease. It can be distinguished from classical urothelial carcinoma microscopically and immunohistochemically. Small cell bladder carcinoma has histologically similar properties with other small cell carcinomas in other organs. It has a worse prognosis when compared to urothelial bladder cancer. Multimodal treatments are recommended although there is no widely accepted consensus regarding to the treatment algorithm because of its rarity. In this review, clinical properties and diagnosis of small cell bladder carcinoma, its histopathological and immunohistochemical properties and treatment modalities are examined.

Molecular profiling of non-urothelial bladder cancer: Adenocarcinoma and squamous cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 423-423
Author(s):  
Daniel M. Geynisman ◽  
David Arguello ◽  
Sandeep K. Reddy ◽  
Zoran Gatalica
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Biology ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Histologic Subtypes ◽  
Tumor Profiling

423 Background: Adenocarcinoma (ADA) and squamous cell carcinoma (SCC) are rare and often aggressive histologic subtypes of bladder cancer. For advanced disease, no clear standard therapies exist and NCCN guidelines suggest only fluorouracil, cisplatin, paclitaxel and ifosfamide as possible options. Thus, novel therapies based on underlying tumor biology are needed. The purpose of this study was to identify potential therapeutic options for these histologic subtypes, utilizing multiplatform tumor profiling. Methods: 49 ADA and 24 SCC specimenswere tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), gene amplification (CISH or FISH), and protein expression (immunohistochemistry [IHC]). 52% of cases were from metastatic sites. Results: Both ADA and SCC exhibited high rates of TP53 aberrations (82.4% and 72.7%, respectively). Sequencing revealed mutations in BRCA2 (14.3%), SMAD4 (12.5%), PTEN (11.8%), KRAS (8.7%), NRAS (5.6%), and KIT (5.3%) in ADA. In addition, PIK3CA (21.4%), HRAS (18.2%), BRCA1 (16.7%), BRCA2 (16.7%), and FBXW7 (9.1%) mutations were detected in SCC. Amplification in EGFR (27.3%) and ERBB2/HER2 (16.7%) were found in ACA. Meanwhile, only one ERBB2 (6.3%) amplification was found in SCC using ISH. MET was not amplified in either ACA or SCC. For both ACA and SCC, EGFR had the highest level of protein expression (100% and 85.7%, respectively). Of note, PD-1 (44.4% in both) and PD-L1 (11.1% and 22.2% in ACA and SCC, respectively) were expressed in both subtypes. Although differential rates of somatic alterations, amplification, and protein expression were found between ADA and SCC, only TLE3 was significant (19.2% versus 60.0%, respectively, p = 0.0154). Conclusions: Differential results in gene alteration, amplification, and protein expression imply the potential utility of tumor profiling in guiding therapeutic decision-making in ADA and SCC of the bladder. PIK3CA/AKT/mTOR pathway aberrations are similar to what has been reported in urothelial bladder cancer. Targeting the PD-1/PD-L1 axis may be a therapeutic option. Further studies are warranted in both diseases.

Treatment of metastatic bladder cancer

2017 ◽  
Author(s):  
Fabio Calabrò ◽  
Cora N. Sternberg
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cancer ◽  
Clinical Investigation ◽  
Good Prognosis ◽  
New Drugs ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Molecular Patterns ◽  
The Impact

Although bladder cancer is considered a chemosensitive malignancy, the prognosis of patients with metastatic disease is poor, with a median survival of approximately 12–14 months in good prognosis patients and with cure in only a minority. The addition of new drugs to the standard cisplatin-based regimens has not improved these outcomes. In this chapter, we highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. A better understanding of the underlying biology and the molecular patterns of urothelial bladder cancer has led to clinical investigation of several therapeutic targets. To date, these agents have yet to demonstrate an improvement in overall survival. Urothelial cancer is extremely sensitive to checkpoint inhibition with both anti PD-1 and anti PDL1 antibodies. The future seems brighter with the advent of these new therapies.

Impact of histologic subtype on bladder cancer outcome.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 391-391
Author(s):  
Samuel L Washington ◽  
Thomas Sanford ◽  
Michael S. Leapman ◽  
Maxwell V. Meng ◽  
Sima P. Porten
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Radical Cystectomy ◽  
Small Cell Carcinoma ◽  
Squamous Cell ◽  
Small Cell ◽  
Variant Histology ◽  
The Impact

391 Background: Variant histology is increasingly recognized but its impact on outcomes is less well known compared to urothelial carcinoma (UC). We aim to evaluate the impact of variant histology on bladder cancer outcomes using the National Cancer Database (NCDB), a U.S. population-based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified patients with bladder cancer from 2004 to 2013 treated with radical cystectomy. We compared clinical and pathologic characteristics between those with UC and those with variant histology. Chi-square test was utilized for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used with hazard ratios (HR) and 95% confidence intervals (CI) to identify independent predictors of overall survival. Results: A total of 40,918 patients were identified with mean age 67 years, with male (75%) and Caucasian (90.9%) predominance. Median follow-up was 36.9 months (IQR 16.1-67.5). Squamous cell carcinoma (4.4%), small cell carcinoma (1.6%) and micropapillary (0.9%) were the most common variant histologies. Variant histology was found more commonly in women (35.6% vs 23.4%, p < 0.05), black (8.8% vs 5.6%, p < 0.05), stage pT3 or T4 (67% vs 50.2%, p < 0.05) and node positive (30.8% vs 26.9%, p < 0.05). In adjusted models squamous cell carcinoma (HR 1.3, 95% CI 1.2-1.4), small cell carcinoma (HR 1.6, 95% CI 1.5-1.8) and black ethnicity (HR 1.2, 95% CI 1.1-1.2) were independent predictors of increased mortality risk while micropapillary was associated with decreased risk (HR 0.8, 95% CI 0.7-1.0) after controlling for age, gender, surgical margin status, pathologic T stage, pathologic N stage and history of chemotherapy. All associations remained statistically significant (p < 0.05). Conclusions: Non-urothelial histology was associated with worse overall survival in patients with bladder cancer treated with radical cystectomy; however, contrary to some previous reports, micropapillary variant was associated with lower risk of death. In addition, black ethnicity was associated with worse survival. Further investigation is needed to explore the impact of variant histology as well as other socioeconomic factors on survival after cystectomy.

Young patients with bladder cancer: Outcomes from the National Cancer Database.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 380-380
Author(s):  
Samuel L Washington ◽  
Maxwell V. Meng ◽  
Sima P. Porten
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Young Patients ◽  
Small Cell ◽  
Categorical Variables ◽  
National Cancer Database

380 Background: Bladder cancer (BC) affecting young patients is not well characterized but seems to be increasingly diagnosed. We aim to describe pathologic findings and BC outcomes in patients less than 40 years old using the National Cancer Database (NCDB), a US population based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified 362,091 patients diagnosed with BC from 2004 to 2013. We compared demographic, clinical and pathologic information between those younger and older than 40 years. Univariate analysis was performed using Chi-square test for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used for survival analysis with hazard ratios (HR) and 95% confidence intervals (CI). Multivariable model was used to identify independent predictors of mortality (overall survival, OS). Results: 3,799 patients (1.1%) were 40 or younger with mean age of 34.5 years. Fewer young patients were women (25.2% vs 30.3%, p<0.001). More identified as nonwhite (11.6% vs 7.3%, p<0.001), had lower clinical T stage (cTa 51.4% vs 38.3%, cT1 13.3% vs 19.6; p<0.001), and longer median follow-up (46.4 months IQR 23.3-73.9 vs 35.3 months IQR 16.7-61.6). Age less than 40 (HR 0.3, 95% CI 0.2-0.3), chemotherapy (HR 0.9, 95% CI 0.9-0.9) and cystectomy (HR 0.8, 95% CI 0.8-0.9) were associated with decreased mortality when controlling for clinical characteristics (p<0.001). In sub-analysis of young patients with cystectomy, more had pT0 disease (20.3% vs 18.2%, p=0.005) with squamous cell carcinoma (13.6% vs 4%) and small cell (3.2% vs 1.6%) more prevalent (p<0.001). In adjusted models, squamous cell carcinoma (HR 1.1, 95% 1.1-1.2), small cell carcinoma (HR 1.5, 95% CI 1.4-1.7), RT (HR 1.2, 95% CI 1.!-1.3) and black ethnicity (HR 1.1, 95% CI 1.1-1.2) were independent predictors of worse OS. Conclusions: Younger patients with BC were more commonly non-white, men, and had low stage disease. In young patients undergoing cystectomy, squamous cell carcinoma, small cell carcinoma and black ethnicity were associated with worse OS. Further exploration in this younger patient cohort is needed to better characterize the optimal oncologic management for these patients.

scholarly journals Management of the urethra in urothelial bladder cancer

2013 ◽  
Vol 3 (6-S4) ◽  
pp. 211 ◽  
Author(s):  
Androniki Kanaroglou ◽  
Bobby Shayegan
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Poor Prognosis ◽  
Urothelial Cancer ◽  
Standard Of Care ◽  
Urothelial Bladder Cancer ◽  
Risk Of Recurrence ◽  
Urothelial Bladder ◽  
Bladder Substitution ◽  
Contemporary Management

The standard of care in the management of invasive urothelialcancer of the bladder is radical cystectomy and pelvic lymphadenectomy.Although uncommon, recurrence of disease in the retainedurethra following cystectomy carries a poor prognosis. The needfor assessment of risk of recurrence is greater now than ever withwider adoption of orthotopic bladder substitution. This reviewwill address the contemporary management of the urethra followingcystectomy for urothelial cancer.

scholarly journals Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Franklin C. Lee ◽  
William Harris ◽  
Heather H. Cheng ◽  
Jaideep Shenoi ◽  
Song Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Cancer ◽  
Response Rates ◽  
Complete Response ◽  
Pathologic Response ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Alternative Regimen

Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC) versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) in the neoadjuvant setting.Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0) and any response (≤pT1). Odds ratios were calculated using multivariate logistic regression.Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64),P=0.03) and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64),P=0.01). Seventy-two patients received GC (n=41) or MVAC (n=31). CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58). Any response (≤pT1) was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71).Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC). Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

Differences in survival among non-urothelial bladder cancers: Analyses of SEER 1988-2008.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Jeanny B. Aragon-Ching ◽  
Donald Henson
Keyword(s):  
Squamous Cell Carcinoma ◽  
Survival Rate ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Median Survival ◽  
Squamous Cell ◽  
Cox Regression ◽  
Small Cell ◽  
Urothelial Bladder ◽  
Incident Cases

425 Background: Non-urothelial cancers of the urinary bladder are rare, and typically < 5% incidence. They are generally considered more aggressive without clear guidelines for treatment. Methods: Incident cases of non-urothelial bladder cancers that included squamous cell carcinoma, adenocarcinoma, small cell carcinoma and sarcomas were identified in the SEER (Surveillance, Epidemiology, and End Results) Database. Demographic information, pathologic characteristics and 5-year disease-specific survival were calculated and compared using multivariate Cox regression and Kaplan-Meier curves. Results: A total of 235,537 incident cases of bladder carcinomas were identified in the years 1998 – 2008, of which 3096 cases were squamous cell carcinoma, 1175 were neuroendocrine carcinoma where small cell carcinomas made up the majority with 859 patients, 671 was comprised of adenocarcinomas, representing 0.28%, and sarcomas were 88 cases, making up 0.03% of all cases combined. The majority of patients were White (90%) although more African-Americans (15%) were seen with adenocarcinoma. The table shows the number of cases and 5-year survival according to stage. Median survival was greatest for adenocarcinoma at 179 months with a 5–year survival rate of 58%, followed by sarcomas with a median survival of 23 months, with a 5-year survival rate of 47%, followed by squamous cell carcinomas with a median survival time of 15 months and a 5-yr survival rate of 37% and the least favorable survival was for small cell carcinoma, 17 months median time, with a 5-yr survival rate of 31%. Conclusions: Non-urothelial cancers have a uniformly less favorable survival compared to urothelial cancers, highlighting the need for improved therapeutic strategies in these cohorts of patients. [Table: see text]

scholarly journals Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 302 ◽  
Author(s):  
Stojnev ◽  
Krstić ◽  
Čukuranović Kokoris ◽  
Conić ◽  
Petković ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Grade ◽  
Disease Assessment ◽  
Prognostic Impact ◽  
Urothelial Bladder Cancer ◽  
Smad4 Expression ◽  
Divergent Differentiation ◽  
Urothelial Bladder ◽  
Tgf Β1

Background and objectives: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods: Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results: High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage (p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade (p = 0,003, p = 0.048, respectively), and low tumor stage (p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors (p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death (p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression (p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival (p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions: Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this disease. Assessment of TGF-β pathway status in patients with urothelial bladder cancer may provide useful prognostic information, and identify patients that could have the most benefit from therapy targeting TGF-β signaling cascade.

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