Urinary tract cancer most commonly involves the bladder, although it may also occur in the renal pelvis, ureters, and, rarely, the urethra. The most common histological type of urinary tract cancer is urothelial carcinoma, followed by squamous cell carcinoma and adenocarcinoma. Symptomatic patients often present with painless gross hematuria and/or irritative voiding symptoms. Urinary tract cancer may also be diagnosed in patients with an incidental finding of microhematuria. All patients with unexplained gross hematuria should be evaluated for urinary tract carcinoma, while patients with microhematuria should undergo risk stratification to determine the need for further evaluation. Diagnostic evaluation includes laboratory studies, imaging, and direct visualization with collection of biopsy samples. Treatment selection is guided by histology, location, and tumor grade and stage. Upper urinary tract carcinomas (i.e., in the renal pelvis and/or ureters) and urethral carcinomas are rare, and there are no standardized treatment protocols. For bladder cancer, nonmuscle invasive disease is treated with transurethral resection of the bladder tumor (TURBT) and either intravesical chemotherapy or bacillus Calmette-Guérin (BCG). Muscle invasive bladder cancer is usually treated more aggressively with neoadjuvant chemotherapy followed by radical cystectomy. Metastatic bladder cancer is managed with palliative chemotherapy. Disease recurrence is common; therefore, close follow-up surveillance is required.
- Sex: : ♂ > ♀ 
- Peak incidence: 60–70 years 
- Cancer sites
- Transitional cell (urothelial) carcinoma: most common (∼ 95%) type of cancer of the bladder, ureter, renal pelvis, and proximal urethra in male individuals
- Squamous cell carcinoma: most common (∼ 60%) type of cancer of the distal urethra in male individuals and the entire urethra in female individuals
- Adenocarcinoma: the rarest type of urinary tract cancer (< 5%) 
Epidemiological data refers to the US, unless otherwise specified.
Transitional cell urothelial carcinoma 
- Tobacco (esp. due to 2-naphthylamine in cigarette smoke)
- Aromatic amines (e.g., benzidine, aniline dye, azo dye, arylamines)
- Heavy metals (e.g., chlorine and arsenic content in drinking water) 
- Polycyclic aromatic hydrocarbons
- Medical procedures
- Genetic predisposition: personal and family history of urothelial carcinoma (e.g., hereditary nonpolyposis colorectal cancer)
Squamous cell carcinoma 
- Medications: cyclophosphamide
- Medical procedures
- Infection: chronic inflammation of the urinary tract that can lead to the transformation of urothelial cells into squamous epithelial cells (squamous metaplasia)
|Clinical features of urinary tract cancer|
|Location||Symptoms||Features of advanced/metastatic disease|
Carcinoma of the renal pelvis and ureteral carcinoma
Perform initial laboratory studies.
- Identify and treat any benign causes of symptoms (e.g., infection) and then reassess.
- For persistent abnormalities, assessment depends on the symptoms.
- If the diagnosis is confirmed, perform staging studies for urinary tract cancer.
Initial laboratory studies
Gross hematuria or microhematuria with ≥ 3 RBCs per high-power field (HPF) 
- Assess for common causes of hematuria ; repeat studies after treatment or cessation of any contributing factors.
- Persistent gross hematuria
- Persistent microhematuria: See “Assessment of microhematuria.”
- Microhematuria with < 3 RBCs per HPF: Repeat urinalysis three times at 6-week intervals. 
Assessment of urine tumor markers is not recommended, as their diagnostic value is uncertain. 
Blood tests 
Direct visualization (cystoscopy/ureteroscopy) 
- Characteristic findings 
Direct visualization is the gold standard for diagnosing urinary tract cancer. 
- Not routinely required: Histology is usually performed on tissue removed during TURBT.
- Image-guided or endoscopic biopsy may be used as an alternative.
- For findings, see “Pathology of urinary tract cancers.”
Urine cytology 
- Indication: an adjunct study for patients with gross hematuria 
- Findings: can detect sloughed malignant cells, especially from high-grade urothelial tumors 
Staging studies for urinary tract cancer 
- First line
- Consider additional studies.
Examination under anesthesia may be used to determine locoregional extension. 
- Asymptomatic microhematuria is less commonly associated with cancer than gross hematuria. 
- Patients should be evaluated for glomerular causes (see “ ); if present patients should be additionally worked up by nephrology. 
- Assessment for urinary tract cancer is based on risk stratification.
Risk stratification for microhematuria
(all criteria must be fulfilled)
(if any of the following are present)
(if any of the following are present)
|Age (years)|| || || |
|Smoking history (pack-years)|| || || |
|RBCs per HPF on urine microscopy|| || || |
| || || |
Risk-based assessment of microhematuria 
Papillary urothelial carcinoma
- A thick papilla with a fibrovascular core
- CIS: focal or diffuse erythematous, flat, velvety lesion(s) in the bladder mucosa 
- Low-grade tumors: usually pedunculated with a papillary surface; and noninvasive 
- High-grade tumors: usually sessile and nodular/solid; and invasive (invading lamina propria or deeper tissues) 
- Squamous cell carcinoma
- Treatment usually consists of surgical resection along with neoadjuvant chemotherapy and/or radiation therapy.
- Metastatic disease is managed with palliative systemic chemotherapy, and, in some cases, palliative surgery (e.g., removal of urethral obstructions).
Treatment of bladder cancer
Nonmuscle invasive 
- First line: transurethral resection of bladder tumor (TURBT)
- Additional treatments include:
Nonmetastatic muscle invasive 
- First-line treatment
- For patients who are ineligible for radial cystectomy or prefer to retain their bladder, bladder-preserving treatment involves a combination of:
Metastatic disease 
- First line: palliative cisplatin-based systemic chemotherapy 
- Palliative immunotherapy, radiation therapy, and/or surgery may also be used. 
Treatment of carcinoma of the renal pelvis and ureters 
- Upper urinary tract cancer is rare and there are no standardized treatment protocols.
- Surgical treatments include:
- Radical nephroureterectomy with or without regional lymphadenectomy: gold standard for high-grade tumors 
- Kidney-sparing alternatives
- Medical treatments include:
Treatment of urethral carcinoma 
- Urethral cancer is rare and there are no standardized treatment protocols.
- Treatment is overseen by a specialist using a combination of the following:
- Urothelial carcinoma commonly recurs; therefore, close monitoring for recurrence and progression is required. 
- Surveillance studies may include repeat cystoscopy, imaging, and laboratory studies (e.g., urine cytology).
- The frequency of surveillance depends on patient characteristics and disease features (e.g., tumor grade and stage).
Routine screening for bladder cancer in asymptomatic adults is not recommended