Pathology Of Bladder Cancer Research Articles

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial

IntroductionPreviously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention.MethodsThis is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS).ResultsFrom the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433–1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511–2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219–2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564–2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS.ConclusionDespite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

Abstract IA022: AI in bladder cancer pathology and research: What can we expect and what not?

Abstract Artificial intelligence (AI) applications are rapidly evolving, disruptive technologies that recently attracted tremendous public awareness including euphoria, bull runs at stock exchanges but also criticism and skepticism. Pathology, a crucial clinical diagnostic discipline, faces significant challenges despite its critical role and broad scope. A notable issue is the declining interest among medical graduates in pursuing further training in Surgical Pathology and Molecular Pathology. This disinterest is compounded by a trend towards part-time work and the aging demographic in Western industrial nations, which increases the demand for precise cancer diagnoses, molecular pathology and advanced oncological treatments. As the need for skilled pathologists grows, the availability of these professionals is steadily decreasing. Furthermore, political policies in heavily regulated healthcare systems (e.g., Germany) are exacerbating the shortage by limiting residency and specialist training positions despite the growing need. Adding to the reluctance among medical graduates to consider pathology as discipline is the looming “threat”” of replacing the field with Artificial Intelligence (AI) technologies. However, historical precedents suggest that necessity often spurs significant innovation. AI's role in pathology is expanding, reshaping the field with new technological advancements. AI, broadly encompassing various computational algorithms designed to perform tasks typically requiring human intelligence such as learning, reasoning, and pattern recognition, is now being applied extensively across different domains including medical diagnostics. Recent implementations in pathology include AI-driven algorithms that automate processes such as the Gleason grading of prostate biopsies, lymph node metastasis detection, detection of molecular bladder cancer subtypes or grading of kidney cancer showing high accuracy levels, speed and reproducibility in delivering results. These tools, while they do not replace pathologists, significantly reduce their workload by automating routine tasks, thus freeing up time for more complex diagnostic activities or simply dealing with the increasing workload. Despite the exciting possibilities, the use of AI in predicting molecular alterations, such as FGFR3 mutations in bladder cancer, faces limitations due to insufficient sensitivity and specificity, indicating that such technologies are not yet suitable for screening purposes. In conclusion, AI is increasingly vital in addressing the challenges of modern pathology, particularly in compensating for the shortage of pathologists. As technology advances, its integration into clinical practice offers promising solutions to enhance diagnostic accuracy and efficiency in uropathology, paving the way for more personalized and effective patient care. Citation Format: Markus Eckstein. AI in bladder cancer pathology and research: What can we expect and what not? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA022.

Research progress in molecular pathology of bladder cancer

Research progress in molecular pathology of bladder cancer

Precision Medicine in Bladder Cancer: Present Challenges and Future Directions.

Bladder cancer (BC) is characterized by significant histopathologic and molecular heterogeneity. The discovery of molecular pathways and knowledge of cellular mechanisms have grown exponentially and may allow for better disease classification, prognostication, and development of novel and more efficacious noninvasive detection and surveillance strategies, as well as selection of therapeutic targets, which can be used in BC, particularly in a neoadjuvant or adjuvant setting. This article outlines recent advances in the molecular pathology of BC with a better understanding and deeper focus on the development and deployment of promising biomarkers and therapeutic avenues that may soon make a transition into the domain of precision medicine and clinical management for patients with BC.

Six potential biomarkers for bladder cancer: key proteins in cell-cycle division and apoptosis pathways

BackgroundThe bladder cancer (BC) pathology is caused by both exogenous environmental and endogenous molecular factors. Several genes have been implicated, but the molecular pathogenesis of BC and its subtypes remains debatable. The bioinformatic analysis evaluates high numbers of proteins in a single study, increasing the opportunity to identify possible biomarkers for disorders.MethodsThe aim of this study is to identify biomarkers for the identification of BC using several bioinformatic analytical tools and methods. BC and normal samples were compared for each probeset with T test in GSE13507 and GSE37817 datasets, and statistical probesets were verified with GSE52519 and E-MTAB-1940 datasets. Differential gene expression, hierarchical clustering, gene ontology enrichment analysis, and heuristic online phenotype prediction algorithm methods were utilized. Statistically significant proteins were assessed in the Human Protein Atlas database. GSE13507 (6271 probesets) and GSE37817 (3267 probesets) data were significant after the extraction of probesets without gene annotation information. Common probesets in both datasets (2888) were further narrowed by analyzing the first 100 upregulated and downregulated probesets in BC samples.ResultsAmong the total 400 probesets, 68 were significant for both datasets with similar fold-change values (Pearson r: 0.995). Protein-protein interaction networks demonstrated strong interactions between CCNB1, BUB1B, and AURKB. The HPA database revealed similar protein expression levels for CKAP2L, AURKB, APIP, and LGALS3 both for BC and control samples.ConclusionThis study disclosed six candidate biomarkers for the early diagnosis of BC. It is suggested that these candidate proteins be investigated in a wet lab to identify their functions in BC pathology and possible treatment approaches.

Methods of creation of bladder cancer models and their application in preclinical studies (literature review)

Purpose of the study to summarize available data on methods for creating bladder cancer models for their application in preclinical studies.Material and methods. A systematic literature search was conducted in the Elibrary, Pubmed, Googlescholar, CyberLeninka databases.Results. The review shows current data on various bladder cancer models and their application in practice. Bladder cancer pathology, identification of diagnostic markers and the development of new therapies are of the main challenges facing the management of bladder cancer. To solve these problems, it is often necessary to conduct preclinical studies using experimental models.Conclusion. Bladder cancer models that can fully reproduce a human disease in terms of histology and behavior are necessary to study the factors involved in cancer development, progression and metastasis. For this, various experimental models are currently used. Human tumor xenografts in mice are widely used. They can reproduce the main pathophysiological features of cancer biology. However, it is necessary to clearly present all the pros and cons of the selected experimental models. The literature review presents modern data on the etiology of bladder cancer, results of preclinical studies on various experimental models, including orthotopic and heterotopic xenografts.

Uptake of re-resection in T1 bladder cancer: An interrupted population-based time series analysis among different groups of surgeons.

A second transurethral resection of the bladder tumor (TURBT) within 2 - 6 weeks after initial TURBT is thought to have diagnostic, therapeutic, and prognostic benefits in T1 bladder cancer (BC). However, little is known about the real-world uptake of this guideline-endorsed intervention. We aimed (1) to measure re-resection rates over time, (2) to investigate if a guideline revision (April 2008) explicitly endorsing re-resection within 2 - 6 weeks in all T1 BC patients led to an increase in re-resection rates, and (3) to investigate the uptake among different groups of surgeons. Province-wide BC pathology reports (January 2001 to December 2015; Ontario, Canada) were linked with health administrative data to (1) identify primary cases of T1 BC and to (2) ascertain whether these patients received re-resection. The resulting patients were then aggregated into quarterly time series and investigated by descriptive analysis, interventional autoregressive moving average (ARIMA) modeling, and Poisson regression analysis. A cohort of 7,373 patients was aggregated into a time series. We observed a linear increase in re-resection rates from 8.4% in 2001 to 28.3% in 2015. An actual effect of the guideline revision in April 2008 on re-resection rates could not be detected (P = 0.41). However, we observed a rather heterogeneous uptake behavior among different groups of surgeons. Specifically, female surgeons, more junior surgeons, high-volume surgeons, Canadian graduates, and surgeons without an academic affiliation were all independently more likely to re-resect their patients (all P-values < 0.05 in adjusted analysis). Re-resection rates in primary T1 BC increased between 2001 and 2015 in the province of Ontario regardless of the guideline revision in April 2008. Our study demonstrates that the uptake of this guideline-endorsed intervention varies among different groups of surgeons and therefore warrants further research to identify barriers to change that can be addressed by tailored interventions.

Factors Associated with Re-Resection in T1 Bladder Cancer: Identifying Patients Who Do Not Receive Guideline-Concordant Care at the Population Level.

Prior research has shown that concordance with the guideline-endorsed recommendation to re-resect patients diagnosed with primary T1 bladder cancer (BC) is suboptimal. Therefore, the aim of this population-based study was to identify factors associated with re-resection in T1 BC. We linked province-wide BC pathology reports (January 2001 to December 2015) with health administrative data sources to derive an incident cohort of patients diagnosed with T1 BC in the province of Ontario, Canada. Re-resection was ascertained by a billing claim for transurethral resection within 2 to 8 weeks after the initial resection, accounting for system-related wait times. Multivariable logistic regression analysis accounting for the clustered nature of the data was used to identify various patient-level and surgeon-level factors associated with re-resection. P values <0.05 were considered statistically significant (2-sided). We identified 7,373 patients who fulfilled the inclusion criteria. Overall, 1,678 patients (23%) underwent re-resection. Patients with a more aggressive tumor profile and individuals without sufficiently sampled muscularis propria as well as younger, healthier and socioeconomically advantaged patients were more likely to receive re-resection (all p <0.05). In addition, more senior, lower volume and male surgeons were less likely to perform re-resection for their patients (all p <0.05). Only a minority of all patients received re-resection within 2 to 8 weeks after initial resection. To improve the access to care for potentially underserved patients, we suggest specific knowledge translation/exchange interventions that also include equity aspects besides further promotion of evidence-based instead of eminence-based medicine.

Perspective: Humanized Pig Models of Bladder Cancer

Bladder cancer (BC) is the 10th most common neoplasia worldwide and holds expensive treatment costs due to its high recurrence rates, resistance to therapy and the need for lifelong surveillance. Thus, it is necessary to improve the current therapy options and identify more effective treatments for BC. Biological models capable of recapitulating the characteristics of human BC pathology are essential in evaluating the effectiveness of new therapies. Currently, the most commonly used BC models are experimentally induced murine models and spontaneous canine models, which are either insufficient due to their small size and inability to translate results to clinical basis (murine models) or rarely spontaneously observed BC (canine models). Pigs represent a potentially useful animal for the development of personalized tumors due to their size, anatomy, physiology, metabolism, immunity, and genetics similar to humans and the ability to experimentally induce tumors. Pigs have emerged as suitable biomedical models for several human diseases. In this sense, the present perspective focuses on the genetic basis for BC; presents current BC animal models available along with their limitations; and proposes the pig as an adequate animal to develop humanized large animal models of BC. Genetic alterations commonly found in human BC can be explored to create genetically defined porcine models, including the BC driver mutations observed in the FGFR3, PIK3CA, PTEN, RB1, HRAS, and TP53 genes. The development of such robust models for BC has great value in the study of pathology and the screening of new therapeutic and diagnostic approaches to the disease.

Superior molecular pathology of urothelial bladder cancer using urinary cell-free DNA.

491 Background: Both urinary and blood cell-free DNA (cfDNA) have been implicated in noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, a direct comparison of their diagnostic performance in the real-world setting is lacking. Methods: 59 eligible cases with pathologically confirmed disease and accompanying tissue/urine pairs were prospectively enrolled and consented to Institutional Review Board-approved protocols. Baseline peripheral blood mononuclear cell (PBMC) and plasma specimens were collected during clinic visit. The 180-gene Predicine liquid biopsy assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tumor tissue-based DNA (tDNA), urinary cfDNA (ucfDNA) and blood cfDNA (bcfDNA). Results: The 59 studied subjects constituted a natural UBC cohort of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), including 48 (81.4%) NMIBC and 42 (71.2%) male patients. Diverse quantitative metrics such as VAF (variant allele frequency) and TMB (tumor mutational burden) were invariably concordant between tDNA and ucfDNA, but not bcfDNA. The mutational landscape captured by tDNA or ucfDNA highly resembled each other and mirrored previously described genomic panorama of UBC, whereas a significant proportion of bcfDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed variants as the ground truth, ucfDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value (PPV) of 67.2%, a negative predictive value (NPV) of 99.8%, and a diagnostic accuracy of 99.1%, which were generally lower in the case of bcfDNA analysis. Conclusions: Urine-based molecular pathology provides valid and complete genetic information about neoplastic lesions, and represents a faithful surrogate for genotyping and monitoring UBC.

Report From the International Society of Urological Pathology (ISUP) Consultation Conference On Molecular Pathology Of Urogenital Cancers. II. Molecular Pathology of Bladder Cancer

During the 2019 International Society of Urological Pathology Consultation Conference on Molecular Pathology of Urogenital Cancer, the Working Group on Bladder Cancer presented the current status and made recommendations on the diagnostic use of molecular pathology, incorporating a premeeting survey. Bladder cancers are biologically diverse and can be separated into "molecular subtypes," based on expression profiling. These subtypes associate with clinical behavior, histology, and molecular alterations, though their clinical utility has not been demonstrated at present and use in bladder cancer is not recommended. Mutations in the TERT promoter are present in the majority of bladder cancers, including the noninvasive stage of tumor evolution, but not in reactive conditions. Mutational analysis of the TERT promoter thus distinguishes histologically deceptive cancers from their benign mimics in some cases. A minority of pathologists employ this test. FGFR3 mutations are common in bladder cancer, and metastatic urothelial carcinoma (UC) with such mutations frequently responds to erdafitinib, an FGFR inhibitor. Testing for FGFR3 alterations is required before using this drug. Metastatic UC responds to immune-oncology (IO) agents in 20% of cases. These are approved as first and second-line treatments in metastatic UC. Several biological parameters associate with response to IO agents, including tumor mutational burden, molecular subtype, and infiltration by programmed death-ligand 1-positive lymphocytes, detected by immunohistochemistry. Programmed death-ligand 1 immunohistochemistry is mandatory before administering IO agents in the first-line setting. In conclusion, much has been learned about the biology of bladder cancer, and this understanding has improved the care of patients with the disease.

Depletion of CDC5L inhibits bladder cancer tumorigenesis.

Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, CDC5L was also found to act as a candidate oncogene in osteosarcoma and cervical tumours. However, the role of CDC5L expression in bladder cancer remains unclear. Here, we analysed the expression and clinical significance of CDC5L in bladder cancer tissues. The expression of CDC5L in fresh bladder cancer tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in bladder cancer. The expression of CDC5L was significantly associated with bladder cancer pathology grade and Ki67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for the survival of bladder cancer patients. To determine whether CDC5L could regulate the proliferation of bladder cancer cells, we transfected bladder cancer cells with an interfering RNA targeting CDC5L and then investigated cell proliferation with a cell counting kit (CCK)-8, flow cytometry assays, colony formation and xenograft assay analyses. Our results indicate that knockdown of CDC5L inhibits proliferation of bladder cancer cells. In addition, reduced expression of CDC5L induced apoptosis of bladder cancer cells and inhibited their migration, invasion and EMT. These findings suggest that CDC5L might play an important role in bladder cancer and thus be a promising therapeutic target of bladder cancer.

KIF20A Affects the Prognosis of Bladder Cancer by Promoting the Proliferation and Metastasis of Bladder Cancer Cells.

Objective To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients. Methods Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot. Immunohistochemical (IHC) staining was used to identify the expression and distribution of KIF20A proteins in the tissue samples. The relationship between the KIF20A expression and the clinical pathology of bladder cancer was analysed. The effect of the differential expression of KIF20A on the prognosis of patients with bladder cancer was analysed by the TCGA database. The plasmid was transfected into the bladder cell lines T24 and 5637 to construct two stable cell lines with knocked down KIF20A. The effect of KIF20A expression on the proliferation and invasion of T24 and 5637 bladder cells was explored in vitro using the abovementioned stable cell lines. The effect of the KIF20A expression on the proliferation of bladder cancer cells was evaluated by a mouse xenograft model. Results The expression of KIF20A was significantly higher in the bladder cancer tissues than in the adjacent control tissues. The expression of KIF20A was significantly associated with the degree of pathological differentiation of bladder cancer. Patients with a higher expression of KIF20A had a higher tumour grade and a more advanced stage. The mean survival of patients with a high KIF20A expression was significantly lower than the mean survival of patients with a low KIF20A expression. The in vitro experiments demonstrated that the knockdown of KIF20A significantly inhibited T24 and 5637 cell proliferation and invasion. The in vivo experiments showed that the knockdown of KIF20A significantly inhibited the proliferation of the bladder tumours. Conclusion KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. KIF20A may become an independent factor that affects the prognosis of bladder cancer patients and a therapeutic target for bladder cancer.

Analysis of ceRNA network identifies prognostic circRNA biomarkers in bladder cancer.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis. Using bioinformatics method to analysis GEO databases (GSE37815, GSE39093, GSE97239, and GSE92675) for differentially expressed RNAs in bladder cancer and normal bladder tissues were screened from. The related volcanic maps and the interaction network maps of differentially expressed RNAs were drawn, and the mRNA-miRNA and miRNA-circRNA interaction were predicted to establish mRNA-miRNA-circRNA competitive endogenous RNA (ceRNA) network. The differential circRNAs related to prognosis of bladder cancer patients were screened based on the influence of miRNA interacting with the circRNA above on survival rate. The expression of miRNA (hsa-mir-214), circRNA (hsa_circ_0076704, hsa_circ_0081963, hsa_circ_0001361) in bladder cancer tissues, adjacent tissues, bladder cancer cells and normal bladder epithelial cells were validated by qRT-PCR. Kaplan Meier curve analysis confirmed the relationship between circRNA (hsa_circ_0076704) and overall survival and prognosis of bladder cancer patients. Through database screening and analysis, we found 19231 differentially expressed genes, 847 differentially expressed miRNAs, 7282 differentially expressed circRNAs. The establishment of ceRNA network consisted of 28 DERNAs (differentially- expressed RNAs), 12 Demi-RNAs and 12 DEcircRNAs. Further prognostic analysis showed that circRNA interacted miRNA hsa-miR-106b, hsa-miR-145 and hsa-miR-214 were associated with overall survival in patients with bladder cancer (P < 0.05). Among them, hsa_circ_0076704, hsa_circ_0081963 and hsa_circ_0001361 are potential circRNA related to OS in bladder cancer and expressed in bladder cancer. The expression of hsa-mir-214 was contrary. Further Kaplan Meier survival analysis showed that hsa_circ_0076704 had significant prognostic value (P < 0.05). In conclusion, hsa_circ_0076704 is independent prognostic factor for bladder cancer.

Downregulation of hsa_circ_0000285 serves as a prognostic biomarker for bladder cancer and is involved in cisplatin resistance.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.

The significance of BLCA-4 in early diagnosis and postoperative monitoring of tumor recurrence in patients with bladder cancer

Objective To investigate the clinical significance of urinary bladder cancer specific nuclear matrix protein-4 (BLCA-4) for the diagnosis of bladder cancer and postoperative monitoring of bladder cancer recurrence. Methods From February 2012 to January 2016 in our hospital 87 patients with bladder cancer pathology confirmed cases (bladder cancer group), 30 patients with urinary tract benign lesions (benign group) and 30 cases of normal healthy people (control group), and the level of BLCA-4 in urine of three groups and recurrence 24 months postoperatively were detected. One month, 6 months and 24 months before and after surgery, the levels of urinary BLCA-4 were compared. Results Preoperative urine BLCA-4 level of bladder cancer group was significantly higher than that of the benign group and healthy group, the difference was statistically significant (P<0.05). The level of BLCA-4 in benign lesion in urine was significantly higher than that of healthy group (P<0.05). The sensitivity of urine BLCA-4 level in the differential diagnosis of bladder cancer was 95.00% and the specificity was 96.67%, the rate of misdiagnosis 5.00%, the misdiagnosis rate was 3.33%, the area under the ROC curve of AUC value consistency was 0.949, urine BLCA-4 level in the differential diagnosis of bladder cancer and the pathological results was 0.916. The recurrence of postoperative BLCA-4 level 6 months and 24 months in the urine was significantly higher than that for the non-recurrence group (P<0.05). Conclusions BLCA-4 level of urine in the differential diagnosis of bladder cancer has a certain clinical value, postoperative monitoring is conducive to the early detection of postoperative recurrence. Key words: Urinary Bladder Neoplasms; Nuclear Matrix-Associated Proteins; Neoplasm Recurrence, Local

Bladder Cancer: New Insights into Its Molecular Pathology.

Bladder cancer is one of the most prevalent cancers worldwide. Unfortunately, there have been few advances in its clinical management due to a poor understanding of the correlations between its molecular and clinical features. Mounting evidence suggests that bladder cancer comprises a group of molecularly heterogeneous diseases that undergo a variety of clinical courses and possess diverse therapeutic responses. Owing to the close association between its molecular subtypes and clinicopathological features, specific therapeutic strategies have recently been suggested. This review summarizes the current understanding of the molecular pathology of bladder cancer, including its molecular biomarkers/pathways and molecular subtypes that have been newly identified using high-throughput technologies. It also discusses advances in our understanding of personalized treatments for specific molecular subtypes.

Does Bladder Cancer Pathology Matter in Prognosis and Treatment?

Context: Neuroendocrine tumors of the bladder are rare, accounting for 0.35- 0.7% of all bladder cancers. Small cell carcinoma of the bladder is a type of neuroendocrine tumor, and it accounts for 0.5- 1% of all tumors of the bladder in some reports, and 0.53% other reports. It is a highly aggressive tumor that presents with nonspecific symptoms. Overall survival of non-metastatic disease is estimated to be about 20.7 month. The survival rate becomes much lower in metastatic disease, with 1-year survival rate about 30%. Case Report: A 74-year-old ex- smoker male patient presents to the hospital with the chronic complaint of back pain, and a new complaint of urine retention and dark urine. Lumbar spine MRI showed extensive vertebral metastasis and spinal canal stenosis. Cystoscopy showed a large bladder tumor with evident muscle invasion (clinical T3 stage by cystoscopy). Further evaluation showed liver, osseous, adrenal and retroperitoneal metastasis in addition to diffuse bony involvement. The patient received palliative radiotherapy in addition to 4 cycles of chemotherapy (carboplatin- etoposide) with subsequent progression. The patient was planned to start Nivolumab immunotherapy, however, he passed away before that. Conclusion: SCCB is a highly malignant NET, usually presenting with symptoms suggestive of advanced disease. Bad prognostic factors include age >60 ears, metastatic disease, local vascular and perineural invasion. Clinical trials addressing specifically SCCB and its treatment are rare. SCCB is often treated according to small cell lung cancer guidelines with platinum-based and etoposide chemotherapy, with poor outcomes in metastatic disease. Some clinicians consider immunotherapy with (Nivolumab) as a last resort in addition to palliative radiotherapy.

Urinary Bladder Thickness, Tumor Antigen, and Lower Urinary Tract Symptoms in a Low Schistosoma Haematobium-Endemic Rural Community of Nigeria

Objective: Bladder tumor antigen (BTA) is a common biomarker for urothelial carcinoma while bladder wall thickening (BWT) is a sign of urinary bladder irritation which suggests cystitis or early-stage bladder cancer pathology, most especially in the absence of bladder outlet obstruction. The aim of this study was to find the incidence of urinary bladder thickness and evaluate the relationship between BTA and BWT in a low schistosomiasis-endemic Nigerian village. Materials and Methods: The study was descriptive and cross-sectional. Freshly passed mid-day urine samples of 56 individuals were screened using chemical reagent strips and then diagnosed microscopically for Schistosoma haematobium. Subsequent follow-up involving ultrasound examination was carried out on distended bladder. The lower urinary tract symptoms (LUTS) were also recorded. Urinary BTA analysis was carried out on the urine samples using enzyme-linked immunosorbent assay. Results: The prevalence of urogenital schistosomiasis in the area was 3.6%. The overall prevalence of human BTA and BWT in the individuals was 44.6 and 35.7%, respectively. The LUTS were associated with BWT (P = 0.004; odds ratio = 6.0; 95% confidence interval = 1.8–20.3). BTA, BWT, and LUTS were not sex and age dependent (P &gt; 0.05). In addition, there was no association between urinary BTA, BWT, and LUTS (P &gt; 0.05). The sensitivity of BWT and LUTS (60.0%) was improved than when either was used to diagnose BTA. Conclusion: The high occurrence of BTA and BWT in the individuals suggests that they may be prone to urothelial carcinoma and urinary bladder irritation, respectively. The role of urogenital schistosomiasis in urinary BTA levels needs to be further explored.

Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research

To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data.