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Other meanings of Urothelial carcinoma

Oncology

Urothelial carcinoma

Urothelial carcinoma, also known as transitional cell carcinoma, is a cancer that arises from the urothelium, the epithelial lining of the urinary tract, most commonly affecting the bladder. It accounts for about 90% of all bladder cancers and can also occur in the renal pelvis, ureters, and urethra. The disease ranges from non-invasive papillary lesions to invasive and metastatic tumors, with treatment and prognosis depending on stage and grade.

~90%
of bladder cancers
proportion
~573,000
new cases worldwide in 2020
incidence
~213,000
deaths worldwide in 2020
mortality
~75%
present as non-muscle-invasive
clinical presentation
1

Pathology and molecular subtypes

Urothelial carcinoma is characterized by a papillary or flat growth pattern, with histologic grading based on cellular atypia and architectural abnormalities. The World Health Organization (WHO) classifies it into low-grade and high-grade lesions, the latter carrying a higher risk of progression. Molecular profiling has identified distinct subtypes, including luminal, basal, and neuronal, which correlate with prognosis and response to therapy. 1 Mutations in FGFR3, TP53, and PIK3CA are common, with FGFR3 alterations more frequent in low-grade tumors. 2

2

Clinical presentation and diagnosis

Hematuria, either macroscopic or microscopic, is the most common presenting symptom, occurring in 80–90% of patients. Other symptoms include dysuria, frequency, and urgency, which may mimic urinary tract infection. Diagnosis typically involves cystoscopy with biopsy, urine cytology, and imaging such as CT urography. Urine-based biomarkers, including UroVysion (FISH) and NMP22, are used as adjuncts, though their sensitivity and specificity vary. 3 Staging follows the TNM system, with depth of invasion being the key prognostic factor.

3

Treatment and management

Non-muscle-invasive bladder cancer (NMIBC) is managed with transurethral resection followed by intravesical therapy, typically bacillus Calmette-Guérin (BCG) for high-risk cases. Muscle-invasive disease requires radical cystectomy with urinary diversion, often combined with neoadjuvant cisplatin-based chemotherapy. For metastatic disease, immune checkpoint inhibitors such as pembrolizumab and atezolizumab have become standard, and targeted therapies like erdafitinib are used for FGFR3-mutated tumors. 4 Recent trials have explored antibody-drug conjugates, including enfortumab vedotin, showing improved survival. 5

4

Lesser-known aspects

Urothelial carcinoma can arise in the upper urinary tract, accounting for 5–10% of cases, and is often associated with Lynch syndrome, a hereditary condition that increases risk. 6 Occupational exposure to aromatic amines, such as those in dye and rubber industries, is a well-established risk factor, with a latency period of up to 30 years. 7 A rare variant, plasmacytoid urothelial carcinoma, is highly aggressive and often presents with peritoneal spread. Additionally, the presence of squamous differentiation is associated with a worse prognosis. 8

Glossary

Urothelium
The epithelial lining of the urinary tract, including the renal pelvis, ureters, bladder, and proximal urethra.
Non-muscle-invasive bladder cancer (NMIBC)
Tumors confined to the mucosa or lamina propria, not invading the muscularis propria.
Bacillus Calmette-Guérin (BCG)
An attenuated live vaccine used as intravesical immunotherapy for high-risk NMIBC.
FGFR3
Fibroblast growth factor receptor 3, a gene frequently mutated in low-grade urothelial carcinoma.

This article focuses on urothelial carcinoma as the most common type of bladder cancer, with emphasis on its pathology, clinical features, and management.