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Bladder Cancer: 5 Things to Know
Bladder cancer is the sixth most common cancer in the United States, with approximately 84,870 new cases projected in 2025. This condition is characterized by a high rate of recurrence, particularly among patients with non-muscle-invasive disease, and often requires lifelong surveillance. Bladder cancer is over four times as common in men as in women, with age-adjusted incidence rates of 31.2 and 7.7 per 100,000, respectively, according to SEER data from 2018-2022. This disparity is largely attributed to higher smoking prevalence and increased occupational exposure to carcinogens among men. Most bladder cancers originate in the inner lining of the bladder, with urothelial carcinoma accounting for more than 90% of cases. Although many cases are diagnosed at an early stage, the disease burden remains significant, especially in muscle-invasive and metastatic disease, where outcomes are worse.
Diagnosis typically involves cystoscopy, urine cytology, and cross-sectional imaging such as CT or MRI to assess tumor burden and identify local or distant spread. A biopsy obtained during cystoscopy confirms malignancy and provides critical information for tumor staging, which guides treatment decisions.
Management options range from transurethral resection and intravesical therapy for non-muscle-invasive disease to radical cystectomy and systemic therapies for more advanced cases. These include immune checkpoint inhibitors such as pembrolizumab and fibroblast growth factor receptor-targeted agents like erdafitinib. Emerging research continues to advance biomarker-guided treatment, noninvasive diagnostics, and personalized medicine aimed at improving clinical outcomes.
Here are five things to know about bladder cancer.
1. Artificial Intelligence Is Improving Diagnostic Accuracy and Speed
Artificial intelligence (AI) is playing an increasingly important role in bladder cancer diagnostics by enhancing risk stratification and workflow reproducibility. A 2025 ASCO abstract (MP06-18) described a computational histology AI (CHAI) tool that analyzed digitized H&E-stained histopathology slides to assess tumor morphology and stratify recurrence risk in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) based on tumor morphology. The AI model identified patients at significantly higher risk of high-grade recurrence and demonstrated strong prognostic performance across independent cohorts.
Beyond risk prediction, AI tools like CHAI highlight the broader potential of integrating AI into pathology workflows. These technologies can reduce diagnostic variability, accelerate turnaround times, and support personalized treatment planning by uncovering histologic patterns that may not be easily detectable by human review. Such advances align with the foundational goals of precision oncology — namely, enabling earlier detection, accurate diagnosis, and personalized treatment guided by individual tumor biology.
2. Mitomycin Offers a Noninvasive Option for Recurrent NMIBC
On June 12, 2025, the FDA approved mitomycin intravesical solution as a first-in-class noninvasive treatment for adults with recurrent, low-grade, intermediate-risk NMIBC. Approval was based on robust data from the phase 3 ENVISION trial, which enrolled 228 evaluable patients. At 3 months, 80% of patients achieved a complete response, defined by the absence of visible tumors on cystoscopy and negative urine cytology, with an impressive 82% likelihood of remaining disease-free at 12 months.
Mitomycin intravesical solution is delivered via an office-based, bladder-retentive gel system, providing a nonsurgical, bladder-sparing alternative for patients who face recurrent disease and wish to avoid a repeated transurethral resection of bladder tumor procedure. The therapy offers a meaningful treatment paradigm shift: instead of undergoing invasive surgery under anesthesia, patients receive six weekly outpatient instillations of mitomycin, allowing for easier administration and potentially fewer complications. While the FDA advisory committee raised concerns over reliance on single-arm data, FDA reviewers emphasized the significant patient benefit in avoiding repeat surgeries.
3. NECTIN4 Amplification May Help Guide Therapy Selection in Metastatic Urothelial Cancer
A growing body of research highlights molecular biomarkers as pivotal tools in guiding therapy for advanced urothelial carcinoma. One biomarker gaining significant attention is NECTIN4 amplification, a genomic alteration commonly observed in advanced and metastatic urothelial carcinoma.
Retrospective data from a study by Klümper and colleagues suggest that NECTIN4 gene amplification, identified using a NECTIN4 -specific fluorescence in situ hybridization assay, may serve as a predictive biomarker in metastatic urothelial carcinoma. Among 108 patients with metastatic disease, amplification was observed in approximately 26%. In this study, NECTIN4 amplification was associated with a 96% objective response rate to enfortumab vedotin, an antibody-drug conjugate targeting NECTIN4 , compared with 32% in nonamplified tumors. Patients with amplified tumors also experienced significantly improved overall survival, with a 92% reduction in mortality risk, and longer progression-free survival (12.8 vs 5.6 months).
While findings like these suggest that NECTIN4 amplification holds promise as a predictive biomarker for response to enfortumab vedotin, clinical implementation will require prospective validation, standardized testing methods, and further research to determine its utility across diverse treatment settings and patient populations.
4. NIAGARA Trial Supports Perioperative Durvalumab for Muscle-Invasive Bladder Cancer
The phase 3 NIAGARA trial investigated perioperative durvalumab in combination with neoadjuvant gemcitabine-cisplatin in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). Results presented at ASCO GU 2025 showed a 32% reduction in event-free survival events and a 25% reduction in overall mortality compared with chemotherapy alone. Importantly, the addition of durvalumab also led to higher pathologic complete response rates (37.3% vs 27.5%) and greater circulating tumor DNA clearance, without delaying or compromising radical cystectomy.
These findings support perioperative durvalumab as a potential new standard of care for cisplatin-eligible MIBC. By improving survival outcomes and biomarker-based measures of response, the NIAGARA regimen reflects a precision medicine approach to treatment. Given the FDA's recent approval of this combination, the NIAGARA regimen is well positioned to shift the perioperative treatment paradigm in this setting.
5. Y Chromosome Loss May Influence Immunotherapy Response in Men
A growing body of research suggests that loss of the Y chromosome (LOY), a somatic event observed in up to 40% of male patients with bladder cancer, may play a dual role in tumor behavior and immunotherapy sensitivity. LOY has been associated with a more aggressive disease phenotype, including accelerated tumor growth, immune suppression, and CD8+ T cell exhaustion, factors that impair immune surveillance and contribute to poorer outcomes.
Paradoxically, this immunosuppressive tumor microenvironment may also increase susceptibility to immune checkpoint inhibitors. In both murine and human models, LOY tumors have shown enhanced responsiveness PD-1/PD-L1 blockade, likely due to the exhausted state of tumor-infiltrating T cells.
These findings were further supported by a 2025 study showing that LOY in both cancer and immune cells is associated with worse clinical outcomes and may help stratify patients for immunotherapy trials. While prospective clinical data directly linking LOY to checkpoint inhibitor response in bladder cancer are still emerging, the available evidence highlights LOY as a promising predictive biomarker. Ongoing research aims to validate its utility in guiding treatment decisions and refining immunotherapy strategies for men with urothelial carcinoma.
