Radical cystectomy (RC) with urinary diversion (UD) is associated with substantial morbidity. Enhanced recovery after surgery protocols, increased robotic usage, and improvements in urinary diversion have been evaluated for their effects on health-related Quality of Life (HRQoL), however, results are mixed. How psychosocial traits inherent to the patient influence HRQoL outcomes is unknown in this population.

Trimodality therapy (TMT), consisting of maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy, has emerged as a bladder-sparing alternative to radical cystectomy for select patients with muscle-invasive bladder cancer (MIBC). While each component of TMT plays a critical role, maximal TURBT is foundational to its success. This review examines the importance of maximal TURBT in optimizing oncological outcomes in TMT, discusses its technical nuances, and explores the evidence supporting its role in achieving durable local control and improving survival outcomes in MIBC.

During surveillance of high-risk non-muscle invasive bladder cancer (HR-NMIBC), occult disease can be missed by standard cystoscopy.

In current clinical practice, the use of switch maintenance avelumab is recommended for patients with locally advanced and metastatic urothelial carcinoma who experience favorable responses to first-line chemotherapy.

The presence of cancer in pelvic lymph nodes removed during radical surgery for muscle-invasive bladder cancer (MIBC) is a key determinant of patient outcome. It would be beneficial to predict node status preoperatively to tailor the use of neoadjuvant chemotherapy and extent of lymph node dissection. Of 12 published node status predictors based on tumor RNA expression signatures, none have been successfully validated in subsequent reports. We aimed to validate all published node status predictors and evaluate new prediction models in MIBC. Gene expression data and node status from two MIBC cohorts were used to test 12 published node-predictive signatures. The overlap in differential expression was examined across the two datasets, and new prediction models were tested in cross-validation and by application to the independent cohort. Published node status predictors performed either no better, or only slightly better than chance in the two independent validation datasets (maximum AUC 0.59 and 0.65, and maximum balanced accuracy 0.54 and 0.57). Among very few genes and signatures differentially expressed in the same direction in both data sets we identified upregulation of interferon-response signatures in node negative cases. Transcriptomic predictors trained in one dataset performed poorly when applied to the independent dataset (AUC 0.60-0.62). In this systematic evaluation, neither the 12 published signatures nor our own models reached an adequate performance for clinical node status prediction in independent data. This indicates that the biological determinants of nodal spread are poorly captured by bulk tumor RNA expression profiles.

This study aims to identify specific genotypes within the UK Biobank (UKB) cohort contributing to a genetic predisposition for bladder cancer (UBC). It highlighted the impact of environmental exposures and the broader role of certain genes in UBC development, offering a comprehensive understanding of the genetic basis for UBC susceptibility.

This study aimed to evaluate the impact of lymphovascular invasion (LVI) and histologic subtypes on prognosis following Bacillus Calmette-Guérin (BCG) therapy in high-grade non-muscle invasive bladder cancer (NMIBC).

Alterations in mRNA splicing play a critical role in driving the molecular heterogeneity of many cancers, including urothelial carcinoma, by contributing to disease progression, treatment response, and clinical outcomes. These splicing changes can arise from somatic mutations in core spliceosomal components or through alternative splicing events affecting cancer-associated genes. In this review, we examine how dysregulation of pre-mRNA splicing influences key aspects of urothelial carcinoma biology, including cell proliferation, invasion, metastasis, modulation of the immune microenvironment, metabolism, and therapeutic resistance. We highlight frequently observed splicing-factor mutations and discuss the impact of aberrant splicing and cancer-specific isoforms on prognosis. We also explore splicing alterations associated with susceptibility to urothelial carcinoma and review emerging therapeutic strategies, such as splice-switching oligonucleotides and small molecule spliceosome inhibitors, that offer promising avenues for precision medicine in this disease.

Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).

Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy that accounts for less than 1% of all bladder cancers. In this report, we highlight the clinical manifestations of SCCB (including epidemiology, cystoscopic and imaging findings), summarize insights into the molecular mechanisms underlying its pathophysiology, detail current methods of staging, review local and systemic treatment, and explore novel agents currently in clinical development. Most of the regimens used for SCCB treatment are extrapolated from small cell lung cancer, a more common cancer that shares the neuroendocrine and aggressive clinical phenotype of SCCB. Greater preclinical research can help to elucidate pertinent similarities and differences between SCCB and other neuroendocrine cancers as well as reveal new therapeutic targets, while increased participation of patients with SCCB in clinical trials may provide additional treatment options for patients with this aggressive cancer.

Bladder cancer (BC), one of the most prevalent and aggressive urological malignancies, poses significant challenges in diagnosis, treatment, and recurrence management. Patient-derived organoid provides new directions for the precision diagnosis and treatment of bladder cancer.

The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is intravesical instillations of Bacillus Calmette-Guérin (BCG). Despite completing BCG therapy, up to 40% of patients experience disease recurrence within five years. T cell exhaustion has been associated with poor outcome following treatment with BCG.

Bladder cancer (BC) is a significant global health concern, with non-muscle invasive bladder cancer (NMIBC) comprising 75% of cases at diagnosis. High-risk NMIBC (HR-NMIBC) poses a significant therapeutic challenge due to its high recurrence and progression rates despite Bacillus Calmette-Guerin (BCG) therapy. Radical cystectomy remains the gold standard for BCG-unresponsive cases but is often met with considerable morbidity and patient reluctance. This has driven research into alternative bladder-sparing therapies (BSTs). Emerging BSTs include immune checkpoint inhibitors like pembrolizumab and novel agents such as nadofaragene firadenovec and nogapendekin alfa inbakicept (IL-15). These therapies have demonstrated promising response rates in clinical trials, offering potential for disease management while preserving bladder function. Gene therapies and targeted agents like CG0070 and EG-70 are also gaining traction for their innovative mechanisms. However, most data are derived from early-phase, single-arm studies, necessitating larger, randomised trials for validation. Device-assisted strategies, including hyperthermic and electromotive drug delivery systems, show potential to enhance intravesical therapy efficacy. Despite advancements, challenges remain in balancing efficacy, safety, and cost-effectiveness within diverse healthcare settings. This narrative review highlights the evolving landscape of BSTs for HR-NMIBC, emphasising the need for robust clinical evidence to refine patient selection and optimise outcomes.

Metabolomic research and metabolomics-based biomarkers predicting treatment outcomes in bladder cancer remain limited.

Recently, urinary extracellular vesicles (uEVs) have emerged as promising biomarkers for early diagnosis, prognosis, and treatment monitoring in urothelial carcinoma (UC). uEVs encapsulate nucleic acids, proteins, and other bioactive molecules that reflect the tumor microenvironment, potentially offering a non-invasive approach for real-time cancer assessment.