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Medscape

Rapid Review: Bladder Cancer

Bladder cancer remains one of the most frequently diagnosed cancers of the genitourinary system, and it presents a unique set of challenges. It is marked by high rates of recurrence, varied clinical presentations, and a need for ongoing surveillance long after initial treatment. Patients often face invasive diagnostic procedures and complex treatment pathways, particularly in the case of non-muscle-invasive vs muscle-invasive disease. Intravesical gene-based therapies represent a newly approved class of treatment for patients with high-risk non-muscle-invasive bladder cancer who are unresponsive to BCG. These therapies work by introducing genetic material directly into bladder cells to stimulate local immune responses or alter tumor biology. Administered via catheter into the bladder, they aim to generate therapeutic effects with minimal systemic exposure, offering an organ-sparing option for patients who might otherwise face radical cystectomy. Instead of delivering preformed proteins or cytotoxic agents, intravesical gene-based treatments enable the bladder to produce therapeutic proteins locally. Although the immune checkpoint inhibitor pembrolizumab can be used for BCG-unresponsive bladder cancer, tumor necrosis factors are not specifically recommended by the National Comprehensive Cancer Network (NCCN), nor are radiation-based immunotherapies. Antibody drug conjugates are recommended for other aspects of disease. Learn more about the treatment of non-muscle-invasive disease. Although combination PET/CT with fluorodeoxyglucose is used for primary staging of muscle-invasive bladder cancer, detecting recurrence after radical cystectomy, and detecting lymph node metastasis, it has 'no clinical role' in diagnosing upper-tract urothelial cancer. This is due to the physiologic uptake of FDG in the bladder, and NCCN guidelines specifically recommend against its use for visualizing the anatomy of the upper urinary tract. However, the NCCN does recommend FDG PET/CT for certain other circumstances, such as suggesting it for staging in patients with T2 and ≥ cT3 disease, and for those with suspected metastasis with or without cystectomy. Research is ongoing on using non-FDG agents for PET that have less urinary uptake. Learn more about imaging for bladder cancer. ctDNA assay is a novel noninvasive surveillance tool that has been shown to be able to predict recurrence before traditional radiologic monitoring. Specifically, studies consistently show that ctDNA can detect recurrence at least 2.7 months earlier than traditional clinical methods such as cystoscopy and cytology, and up to up to 6 months before radiologic progression. This gives clinicians a bigger window for offering neoadjuvant therapy, which could improve survival outcomes. Further, ctDNA is shown to be more sensitive than traditional methods and is less invasive than cystoscopy. Although the NCCN notes that ctDNA has demonstrated ultrasensitive capabilities for tracking treatment response and progression, it does not have sufficient data to recommend basing treatment practices on ctDNA assays. Learn more about monitoring for bladder cancer. The NCCN suggests TURBT alone as an option for patients with stage II disease who are ineligible for cystectomy. Even without adjuvant therapy, TURBT alone may be curative in cases with small solitary lesions and minimal muscle invasion. However, it should not be used in cases with an associated in situ component, palpable masses, or associated hydronephrosis. Furthermore, if TURBT alone is used as primary treatment, a second re-resection should be performed 4 weeks after the primary procedure, and then it can be managed conservatively if there is no evidence of residual tumor and the patient is not a candidate for definitive management or prefers bladder preservation. Learn more about TURBT for bladder cancer. FGFR-targeted kinase inhibitors are a precision therapy used in a subset of patients with advanced urothelial carcinoma whose tumors harbor FGFR genetic alterations. These drugs improve clinical outcomes by directly inhibiting the abnormal FGFR signaling pathways that drive tumor growth in these patients. In a phase 2 trial, erdafitinib showed a 40% objective response rate and extended progression-free and overall survival in this biomarker-defined subgroup. By selectively targeting this oncogenic driver, FGFR inhibitors can induce tumor regression and prolong progression-free survival. In regard to the other answer choices, FGFR inhibitors do not stimulate broad immune responses. Also, these therapies require molecular profiling to identify patients with FGFR alterations and act through selective, not cytotoxic or nonspecific, mechanisms. Learn more about medications for bladder cancer.