A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value.

Objective: We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance.

Upper tract urothelial cancer (UTUC) genomic profiling and correlation regarding benefit of platinum-based chemotherapy.

Upper tract urothelial cancer (UTUC) are rare subsets of urothelial cancer, which typically present with more aggressive course. Molecular markers stratifying urothelial tumors as luminal subtype and non-luminal subtype tumors have been proposed to select patients who may have greater or lesser benefit from neoadjuvant systemic therapy in bladder cancer, though not yet evaluated in UTUC. Here, a single-institution study retrospectively obtained clinical and genomic information in patients with UTUC and evaluated four patient tumors using the Decipher Bladder assay and Foundation Medicine test.

A Genomic Urine Assay for Surveillance of Patients with Bladder Cancer Treated with Radiotherapy.

Background: Patients with muscle-invasive bladder cancer (MIBC) who receive radiotherapy with curative intent are followed by imaging, cystoscopy, and urine cytology. However, interpretation of cytology and cystoscopy is hampered by the impact of ionizing radiation on cells.

Objective: To assess the diagnostic performance of a genomic urine assay to detect urinary tract recurrences in patients with MIBC treated by (chemo)radiation.

Alignment of molecular subtypes across multiple bladder cancer subtyping classifiers.

Background: Treatment of patients with muscle-invasive bladder cancer (MIBC) includes cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Molecular subtypes have been associated with patient outcomes after NAC and RC, but the reported results have been highly inconsistent.

Objective: To evaluate the association of molecular subtypes from different classifiers with overall survival (OS) among patients with MIBC who underwent RC.

The Diagnostic Accuracy of Cystoscopy for Detecting Bladder Cancer in Adults Presenting with Haematuria: A Systematic Review from the European Association of Urology Guidelines Office.

Context: Haematuria can be macroscopic (visible haematuria [VH]) or microscopic (nonvisible haematuria [NVH]), and may be caused by a number of underlying aetiologies. Currently, in case of haematuria, cystoscopy is the standard diagnostic tool to screen the entire bladder for malignancy.

Objective: The objective of this systematic review is to determine the diagnostic test accuracy of cystoscopy (compared with other tests, eg, computed tomography, urine biomarkers, and urine cytology) for detecting bladder cancer in adults.

A Urine-based Genomic Assay Improves Risk Stratification for Patients with High-risk Hematuria Stratified According to the American Urological Association Guidelines.

Background: According to the recent American Urological Association (AUA) guideline on hematuria, patients are stratified into groups with low, intermediate, and high risk of urothelial carcinoma (UC). These risk groups are based on clinical factors and do not incorporate urine-based tumor markers.

Objective: To evaluate whether a urine-based genomic assay improves the redefined AUA risk stratification for hematuria.

RNA-based urinary assays for non-muscle invasive bladder cancer.

Purpose Of Review: To provide an overview of the recent literature on RNA-based molecular urine assays for the diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC).

Recent Findings: Articles were eligible for inclusion if performance metrics sensitivity, specificity, and negative-predictive value (NPV) were reported or could be calculated. Only prospective studies published between 2020-2022 were included.

Non-muscle-invasive micropapillary bladder cancer has a distinct lncRNA profile associated with unfavorable prognosis.

Background: Molecular subtyping of bladder cancer has revealed luminal tumors generally have a more favourable prognosis. However, some aggressive forms of variant histology, including micropapillary, are often classified luminal. In previous work, we found long non-coding RNA (lncRNA) expression profiles could identify a subgroup of luminal bladder tumors with less aggressive biology and better outcomes.

Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum Based Neoadjuvant Chemotherapy.

Purpose: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with nonmetastatic muscle-invasive bladder cancer (MIBC) confers an absolute survival benefit of 5%-10%. There is evidence that molecular differences between tumors may impact response to therapy, highlighting a need for clinically validated biomarkers to predict response to NAC.

Materials And Methods: Four bladder cancer cohorts were included.

Molecular subtyping and immune-gene signatures identify a subset of early bladder tumors as candidates for single-agent immune-checkpoint inhibition.

Purpose: Clinical high-grade (HG) T1 non-muscle invasive bladder cancer (NMIBC) represents a significant risk to patients, but these patients are not typically offered neoadjuvant therapies, including immune therapy. In this study, we determine whether patients with HG clinical T1 or T2 bladder urothelial carcinoma (UC) have profiles that predict the potential effectiveness of immune-checkpoint inhibitors (ICI).

Materials And Methods: Data from transurethral resection of bladder tumor (TURBT) specimens from 2 studies was evaluated.

Gene Expression Profiling of Muscle-Invasive Bladder Cancer With Secondary Variant Histology.

Objectives: To determine the potential impact of the presence of secondary variant histology on the gene expression profiles of muscle-invasive bladder cancer (MIBC) tumors.

Methods: For six tumors, revised samples were collected from urothelial and secondary variant components (cohort A). The commercial cohort (cohort B) consisted of the anonymized gene expression profiles of 173 patients with MIBC.

PD-L1 expression in urothelial bladder cancer varies more among specimen types than between companion assays.

Urothelial bladder cancer (UBC) patients ineligible to platinum-based chemotherapy can be treated with immune-checkpoint inhibitors (ICI) in Programmed Death Ligand 1 (PD-L1) positive cases. Although concordance exists between different PD-L1 assays, little is known on PD-L1 expression variability in matched UBC samples. We compared PD-L1 expression in whole slides of matched transurethral resections (TURBT), radical cystectomies (RC), and lymph node metastasis (LN).

Molecular Characterization of Residual Bladder Cancer after Neoadjuvant Pembrolizumab.

Background: In patients with muscle-invasive urothelial bladder cancer (MIBC), molecular alterations in immunotherapy-resistant tumors found at radical cystectomy (RC) remain largely unstudied.

Objective: To investigate the biology of pembrolizumab-resistant tumors in comparison to an RC cohort treated without any systemic therapy and a cohort of neoadjuvant chemotherapy (NAC)-treated tumors.

Design, Setting, And Participants: Transcriptome-wide expression profiling was performed on 26 RC samples from patients with ypT2-4 disease after pembrolizumab treatment, of which 22 had matched pretherapy samples.

Evaluation of the New American Urological Association Guidelines Risk Classification for Hematuria.

Purpose: Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline.

Materials And Methods: This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria.

T1 Substaging of Nonmuscle Invasive Bladder Cancer is Associated with bacillus Calmette-Guérin Failure and Improves Patient Stratification at Diagnosis.

Purpose: Currently, markers are lacking that can identify patients with high risk nonmuscle invasive bladder cancer who will fail bacillus Calmette-Guérin treatment. Therefore, we evaluated the prognostic value of T1 substaging in patients with primary high risk nonmuscle invasive bladder cancer.

Materials And Methods: Patients with primary high risk nonmuscle invasive bladder cancer who received ≥5 bacillus Calmette-Guérin induction instillations were included.

Can Patients with Muscle-invasive Bladder Cancer and Fibroblast Growth Factor Receptor-3 Alterations Still Be Considered for Neoadjuvant Pembrolizumab? A Comprehensive Assessment from the Updated Results of the PURE-01 Study.

In the PURE-01 study, patients with muscle-invasive bladder cancer (MIBC) who achieved a pathological complete response (CR; ypT0N0) had tumor features suggesting that pre-existing immunity may promote response. We focused on fibroblast growth factor receptor-3 (FGFR3) genomic alterations (GAs) as potential tumor resistance features. The primary endpoint of our study was CR.

Correction to: Genomic Subtyping in Bladder Cancer.

The original version of this article contained a mistake. The included Conflict of Interest statement was incorrect.

Distribution of Molecular Subtypes in Muscle-invasive Bladder Cancer Is Driven by Sex-specific Differences.

Muscle-invasive bladder cancer (MIBC) is a sex-biased cancer with a higher incidence in men but worse outcomes in women. The root cause behind these observations remains unclear. To investigate whether sex-specific tumor biology could explain the differences in clinical behavior of MIBC, we analyzed the transcriptome profiles from transurethral resected bladder tumors of 1000 patients.