Context Urothelial carcinoma can exhibit a wide range of variant morphologies. Many variants present diagnostic challenges and carry clinical implications that inform prognosis and treatment decisions. Objective To provide an overview of the diagnostic, therapeutic, and prognostic significance of histological variants of urothelial carcinoma. Evidence acquisition A PubMed/MEDLINE-based literature search was conducted using the key terms “urothelial carcinoma”, “variant histology”, “nested”, “micropapillary”, “microcystic”, “sarcomatoid”, “squamous differentiation”, “glandular differentiation”, “clear cell”, “plasmacytoid”, “lymphoepithelioma-like carcinoma”, “squamous cell carcinoma”, “small cell carcinoma”, “adenocarcinoma”, “radiotherapy”, “neoadjuvant chemotherapy”, and “adjuvant chemotherapy”. Evidence synthesis The incidence of variant histology is increasing due to improved recognition. Nonetheless, diagnosis can pose challenges due to sampling limitations and interobserver variability. Although associated with advanced disease at presentation, survival outcomes for most variants do not differ significantly compared with pure urothelial carcinoma of the same stage. Controversy exists regarding optimal management due to the low quality of available evidence. For most cases, radical cystectomy with pelvic lymph node dissection (with neoadjuvant chemotherapy when appropriate) represents the standard of care. Small cell carcinoma and lymphoepithelioma-like carcinoma appear to be particularly chemosensitive. Conclusions Accurate identification of variant histological subtypes is an important part of risk stratification, as these variants exhibit aggressive biological behaviour. Variant histology tumours are associated with advanced disease at presentation, which must be considered when counselling patients regarding survival outcomes. Optimal management remains to be defined but in most cases; neoadjuvant chemotherapy and radical cystectomy with pelvic lymph node dissection remains the mainstay of treatment. Patient summary It is important to recognise histological variants of urothelial carcinoma as they indicate aggressive disease. When compared with patients with pure urothelial carcinoma of the same disease stage, survival does not appear to be significantly worse. In most cases, patients with invasive variant histology should be treated with neoadjuvant chemotherapy and radical cystectomy. Take Home Messages Accurate identification of variant histology is important as it exhibits aggressive biological behaviour and affects treatment. Although associated with advanced disease at presentation, with appropriate treatment, survival outcomes are not significantly different compared with pure urothelial carcinoma of the same stage.

What Is the Significance of Variant Histology in Urothelial Carcinoma

Bladder cancer (BC) is one of the most common malignancies in terms of incidence and recurrence worldwide The aim of this study was to identify novel prognostic biomarkers related to BC progression utilizing weighted gene co-expression network analysis (WGCNA) and further bioinformatic analysis First, we constructed a co-expression network by using WGCNA among 274 TCGA-BLCA patients and preliminarily screened out four genes (CORO1C, TMPRSS4, PIK3C2B, and ZNF692) associated with advanced clinical traits In support, GSE19915 and specimens from 124 patients were used to validate the genes selected by WGCNA; then, CORO1C and TMPRSS4 were confirmed as hub genes with strong prognostic values in BC Moreover, the result of gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) indicated that CORO1C and TMPRSS4 might be involved in the process of epithelial to mesenchymal transition (EMT) reversely In addition, high expression of CORO1C was found to be significantly correlated with tumor-infiltrating neutrophils (TINs), a negative regulatory component that facilitates tumor distant progression and induces poor clinical outcome In conclusion, our study first identified CORO1C and TMPRSS4 as vital regulators in the process of tumor progression through influencing EMT and could be developed to effective prognostic and therapeutic targets in future BC treatment

/pdf/novel-potential-biomarkers-associated-with-epithelial-to-3750kr8ei3.pdf

Novel Potential Biomarkers Associated With Epithelial to Mesenchymal Transition and Bladder Cancer Prognosis Identified by Integrated Bioinformatic Analysis

Nowadays, an increasing number of studies illustrated that bladder urothelial cancer (BLCA) may act as the most common subtype of urological malignancies with a high rate of recurrence and metastasis. In this study, we attempted to establish a prognostic model and identify the possible pathway crosstalk. Long noncoding RNAs (lncRNAs) and mRNA expression and corresponding clinical information of patients with BLCA were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes analysis, univariate Cox analysis, the least absolute shrinkage, and selection operator Cox (LASSO Cox) regression model were then applied to identify five crucial lncRNAs (AC092725.1, AC104071.1, AL023584.1, AL132642.1, and AL137804.1). The multivariate cox analysis was utilized to calculate the regression coefficients (βi ). The risk-score model was subsequently constructed as follows: (0.13541AC092725.1) + (0.20968AC104071.1) + (0.1525AL023584.1) - (0.14768AL132642.1) + (0.14387AL137804.1). Nomogram and assessment of overall survival (OS) prediction were verificated by the receiver operating characteristic curve in the testing group. As to 3-, 5-year OS prediction, the area under curve (AUC) for the nomogram of training data set was 0.83 and 0.86. Besides, the AUC (0.883 and 0.879) presented excellent predictive power in the testing group. In addition, the calibration plots validated the predictive performance of the nomogram. Weighted correlation network analysis (WGCNA) coupled with functional enrichment analysis contributed to explore the potential pathways, including PI3K-Akt, HIF-1, and Jak-STAT signaling pathways. Construction of the risk-score model and data analysis were both derived from multiple packages on the basis of the R platform chiefly.

Identification of five long noncoding RNAs signature and risk score for prognosis of bladder urothelial carcinoma.

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

Dataset for the reporting of carcinoma of the bladder—cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR)

Pure urothelial carcinoma is the most common histology of bladder cancer, consisting of about 75% of all cases. The remaining cases are represented by histological variants (HVs). Despite an apparent and recent rise in the incidence of variant histology (VH) in pathological reports, the real epidemiology, presentation and prognostic value on oncological outcomes are still not well established. Pathological identification of HVs indeed is challenging and at risk of under-recognition and misclassification, both at transurethral resection (TUR), due to the lack of a standardized technique, and at definitive histology after cystectomy because of the need for dedicated genitourinary pathologists. Genomic sequencing has led to identify molecular subtypes of bladder cancer eventually related to HVs and potentially implicated in the management of bladder cancer. The aim of this review is to present an overview of the literature regarding the impact of VH and molecular subtypes on bladder cancer outcomes. A narrative review of the literature was conducted applying several terms and combinations of them regarding HVs and molecular subtypes. The main findings are that HVs are indicative of a more aggressive disease, often advanced at presentation. When matched for stage and grade, the oncological outcomes are similar with pure urothelial carcinoma, except for pure squamous cell and signet ring cell carcinoma variants that invariably portend a poor prognosis. Radical cystectomy (RC) remains the treatment of choice and should be considered even in non-muscle-invasive cases if some forms of VH are present. Neoadjuvant chemotherapy is recommended in chemo-sensitive variants. Molecular composition could be related to the expression of specific VH and new subtypes could be identified with further investigations. Future developments in TUR procedures, genomic techniques and dedicated genitourinary pathologists will lead to a better definition of each HV, along with related prognosis and response to treatments.

/pdf/the-impact-of-histological-variants-on-bladder-cancer-2k0pisyp6w.pdf

The impact of histological variants on bladder cancer outcomes

To review the United States National Cancer Database (NCDB) from 2004 to 2015 and analyze survival outcomes of invasive non-urachal adenocarcinoma based on treatment modality. The NCDB 2004–2015 bladder dataset was queried for adenocarcinoma histology, excluding urachal variant, and limited to patients with clinical stage T2–T4 disease. Treatment modality was categorized as no treatment, cystectomy (partial or radical), external beam radiation therapy (EBRT), or EBRT plus cystectomy. Our primary outcome was overall survival. Cox regression (CR) and Kaplan–Meier (KM) analysis were performed. 851 patients were identified with invasive (cT2–T4) adenocarcinoma of the bladder. Treatment modalities included 398 (47.8%) no treatment, 298 (35.8%) cystectomy, 124 (14.9%) EBRT, and 31 (3.7%) EBRT plus cystectomy. On KM analysis excluding those with metastatic disease, the 5-year survival was significantly better (p < 0.001) for patients who underwent cystectomy (39.6%), versus no treatment (21.0%), EBRT (18.6%), or EBRT plus cystectomy (26.9%) (log rank, p < 0.001). On CR for mortality, age (HR 1.030, p < 0.001), Charlson score 1 (HR 1.287, p = 0.034), cT4 (HR 1.768, p < 0.001), and receiving treatment at a low-volume center (HR 1.289, p = 0.026) were associated with worsened survival; however, cystectomy (HR 0.593, p < 0.001) was the only factor associated with improved survival. For those undergoing cystectomy, the mean length of stay was 8.5 days and the 30-day readmission rate was 7.0%. Invasive non-urachal adenocarcinoma of the bladder is a rare diagnosis. Survival benefits in patients without metastatic disease are seen only in those patients undergoing definitive surgery.

Invasive non-urachal adenocarcinoma of the bladder: analysis of the National Cancer Database

Objective:Our objective was to analyze patterns of treatment for metastatic renal cell carcinoma (mRCC) (no treatment (NT), cytoreductive nephrectomy only (CN), systemic therapy only (ST), and both...

The current treatment patterns of metastatic renal cell carcinoma: A national cancer database review, 2004–2015:

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Invasive non-urachal adenocarcinoma of the bladder: analysis of the National Cancer Database

The current treatment patterns of metastatic renal cell carcinoma: A national cancer database review, 2004–2015: