PD-L1 expression in high-risk non-muscle invasive bladder cancer is not a biomarker of response to BCG.

Purpose: Up to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1).

Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.

Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

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.

Equipping computational pathology systems with artifact processing pipelines: a showcase for computation and performance trade-offs.

Background: Histopathology is a gold standard for cancer diagnosis. It involves extracting tissue specimens from suspicious areas to prepare a glass slide for a microscopic examination. However, histological tissue processing procedures result in the introduction of artifacts, which are ultimately transferred to the digitized version of glass slides, known as whole slide images (WSIs).

Characterization of FGFR Alterations and Activation in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

Purpose: The Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette-Guérin (BCG) treatment in high-risk non-muscle-invasive bladder cancer (HR-NMIBC). An FGFR predictive response signature (FGFR-PRS) was discovered that identifies patients with an activated FGFR pathway who could potentially benefit from FGFR-targeted therapy beyond those who are FGFR ALT (+).

Experimental Design: Pretreatment tumor samples and clinical data were analyzed from 582 BCG-treated patients with HR-NMIBC.

Multi-Center Assessment of Lymph-Node Density and Nodal-Stage to Predict Disease-Specific Survival in Patients with Bladder Cancer Treated by Radical Cystectomy.

Background: Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed.

Objectives: To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection.

Methods: We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers.

Molecular biomarkers of progression in non-muscle-invasive bladder cancer - beyond conventional risk stratification.

The global incidence of bladder cancer is more than half a million diagnoses each year. Bladder cancer can be categorized into non-muscle-invasive bladder cancer (NMIBC), which accounts for ~75% of diagnoses, and muscle-invasive bladder cancer (MIBC). Up to 45% of patients with NMIBC develop disease progression to MIBC, which is associated with a poor outcome, highlighting a clinical need to identify these patients.

Selecting the right treatment: Health outcome priorities in older patients with bladder cancer.

Introduction: Selecting the appropriate treatment for older patients with non-muscle invasive (NMIBC) or muscle-invasive bladder cancer (MIBC) is challenging due to smoking-related comorbidities, treatment toxicity, and an increased risk of adverse health outcomes. Considering patient preferences prior to treatment is therefore crucial. Here, we aimed to identify the health outcome priorities of older patients with high-risk NMIBC (HR-NMIBC) or MIBC.

NPEPPS Is a Druggable Driver of Platinum Resistance.

Unlabelled: There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits of platinum drugs to a greater number of patients is highly desirable.

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.

Are you sure it's an artifact? Artifact detection and uncertainty quantification in histological images.

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions.

Artificial Intelligence in Digital Pathology for Bladder Cancer: Hype or Hope? A Systematic Review.

Bladder cancer (BC) diagnosis and prediction of prognosis are hindered by subjective pathological evaluation, which may cause misdiagnosis and under-/over-treatment. Computational pathology (CPATH) can identify clinical outcome predictors, offering an objective approach to improve prognosis. However, a systematic review of CPATH in BC literature is lacking.

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.

Non-muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guérin.

The recommended treatment for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. If progression to advanced disease occurs, then patients must undergo a radical cystectomy with risks of substantial morbidity and poor clinical outcome.

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.

Background: BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.

Methods: The aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients.

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.

Risk factors associated with positive surgical margins' location at radical cystectomy and their impact on bladder cancer survival.

Purpose: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC).

Methods: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates.

Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer.

In high-risk non-muscle invasive bladder cancer (HR-NMIBC), patient outcome is negatively affected by lack of response to (BCG) treatment. Lack of response to cisplatin-based neoadjuvant chemotherapy and cisplatin ineligibility reduces successful treatment outcomes in muscle-invasive bladder cancer (MIBC) patients. The effectiveness of PD-1/PD-L1 immune checkpoint inhibitors (ICI) in metastatic disease has stimulated its evaluation as a treatment option in HR-NMIBC and MIBC patients.

Biomarker-Oriented Therapy in Bladder and Renal Cancer.

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials.

Role of Bladder Cancer Metabolic Reprogramming in the Effectiveness of Immunotherapy.

Metabolic reprogramming (MR) is an upregulation of biosynthetic and bioenergetic pathways to satisfy increased energy and metabolic building block demands of tumors. This includes glycolytic activity, which deprives the tumor microenvironment (TME) of nutrients while increasing extracellular lactic acid. This inhibits cytotoxic immune activity either via direct metabolic competition between cancer cells and cytotoxic host cells or by the production of immune-suppressive metabolites such as lactate or kynurenine.