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Key Clinical Updates in Bladder Cancer

Pembrolizumab is FDA-approved for patients with high-risk, non–muscle invasive bladder cancers who have failed intravesical bacillus Calmette–Guérin therapy. Nivolumab has also been approved in the adjuvant setting after radical cystectomy or nephroureterectomy for urothelial carcinoma at high risk for recurrence.

The fibroblast growth factor receptor (FGFR) inhibitor erdafitinib is approved after initial therapy for patients with progressive metastatic urothelial carcinoma whose tumors harbor these mutations with expected response rates of up to 40%.

Enfortumab vedotin is the first antibody-drug conjugate approved for advanced and metastatic urothelial carcinoma. The antibody targets Nectin-4 and demonstrates a 44% response rate (including 12% complete response) in patients who have progressed after multiple other lines of therapy.

Bajorin DF et al. N Engl J Med. [PMID: 34077643]

Balar AV et al. Lancet Oncol. [PMID: 34051177]

Rosenberg JE at al. J Clin Oncol. [PMID: 31356140]

ESSENTIALS OF DIAGNOSIS

  • Gross or microscopic hematuria.

  • Irritative voiding symptoms.

  • Positive urinary cytology in most patients.

  • Filling defect within bladder noted on imaging.

GENERAL CONSIDERATIONS

Bladder cancer is the second most common urologic cancer; it occurs more commonly in men than women (3.1:1), and the mean age at diagnosis is 73 years. In 2022 in the United States, it is estimated that approximately 81,180 cases of bladder cancer will be diagnosed and 17,100 deaths will result. Cigarette smoking and exposure to industrial dyes or solvents are risk factors for the disease and account for approximately 60% and 15% of new cases, respectively. In the United States, almost all primary bladder cancers (98%) are epithelial malignancies, usually urothelial cell carcinomas (90%). Adenocarcinomas and squamous cell cancers account for approximately 2% and 7%, respectively. The latter is often associated with schistosomiasis, vesical calculi, or prolonged catheter use.

CLINICAL FINDINGS

A. Symptoms and Signs

Hematuria—gross or microscopic, chronic or intermittent—is the presenting symptom in 85–90% of patients with bladder cancer (see Hematuria in Chapter 23). Irritative voiding symptoms (urinary frequency and urgency) occur in a small percentage of patients as a result of the location or size of the cancer. Most patients with bladder cancer do not have signs of the disease because of its superficial nature. Abdominal masses detected on bimanual examination may be present in patients with large-volume or deeply infiltrating cancers. Hepatomegaly or palpable lymphadenopathy may be present in patients with metastatic disease, and lymphedema of the lower extremities results from locally advanced cancers or metastases to pelvic lymph nodes.

B. Laboratory Findings

UA reveals microscopic or gross hematuria in the majority of cases. On occasion, hematuria is accompanied by pyuria. Azotemia may be present in a small number of cases associated with ureteral obstruction. Anemia may occasionally be due to chronic blood loss or to bone marrow metastases. Exfoliated cells from normal and ...

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