Urothelial carcinoma presenting with painless hematuria; strongly linked to smoking.
Also known as: bladder cancer, urothelial carcinoma, transitional cell carcinoma, TCC
Overview
Malignancy arising from the urothelium lining the bladder. Urothelial carcinoma (formerly transitional cell carcinoma) accounts for >90% of cases in developed countries. Categorized as non-muscle-invasive bladder cancer (NMIBC; Ta, T1, Tis) — 75% at diagnosis — or muscle-invasive bladder cancer (MIBC; T2+).
Epidemiology
~83,000 new cases and ~17,000 deaths annually in the US. Fourth most common cancer in men. Male:female ratio ~3:1. Median age at diagnosis 73 years. Most cases occur in current or former smokers.
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Carcinogens are concentrated in urine and have prolonged contact with the urothelium. Mutations accumulate in oncogenes (FGFR3 — papillary low-grade tumors) and tumor suppressors (TP53, RB1 — high-grade and muscle-invasive). Field cancerization explains multifocal and recurrent disease throughout the urothelium (ureters, renal pelvis, urethra). NMIBC tumors are slow-growing and recurrent but rarely metastasize; MIBC has rapid progression and metastatic potential.
Clinical presentation
Symptoms
Painless gross hematuria — most common presenting symptom (~80%); intermittent
Microscopic hematuria (often detected on routine UA)
Irritative voiding symptoms — dysuria, frequency, urgency (more common with CIS)
Definitive diagnosis requires cystoscopic biopsy with histologic confirmation. Transurethral resection of bladder tumor (TURBT) provides both diagnosis and initial treatment, with muscularis propria sampling required to stage T category.
Labs
Urinalysis with microscopy — confirms hematuria; rule out infection (urine culture)
Urine cytology — useful for high-grade tumors and CIS; low sensitivity for low-grade (~40%)
Urine tumor markers (NMP22, BTA) — adjunct, not replacement for cystoscopy
BMP, CBC, LFTs
Imaging
Cystoscopy — gold standard diagnostic procedure; allows direct visualization and biopsy
CT urography with multi-phase imaging — evaluates upper tract (5% of urothelial cancers involve renal pelvis/ureters)
MR urography — alternative if contrast contraindicated
MRI pelvis for staging muscle invasion
CT chest/abdomen/pelvis for staging in MIBC
Bone scan or PET if metastasis suspected
Diagnostic algorithm
Stage
Description
Standard Treatment
Ta
Non-invasive papillary, low or high grade
TURBT ± intravesical therapy
Tis (CIS)
Flat, high-grade in situ
TURBT + intravesical BCG
T1
Invades lamina propria
TURBT + BCG (or cystectomy if high-risk)
T2
Invades muscularis propria
Radical cystectomy ± neoadjuvant chemo
T3
Invades perivesical tissue
Radical cystectomy + neoadjuvant chemo
T4
Invades adjacent organs
Chemo + cystectomy or chemoradiation
N+/M+
Lymph node or distant metastasis
Systemic therapy (chemo + immunotherapy)
Bladder cancer staging (TNM) and standard treatment approach by stage.
Treatment
First-line
Non-muscle invasive bladder cancer (NMIBC; Ta, T1, Tis):
Transurethral resection of bladder tumor (TURBT) — complete excision with muscularis propria sample
Single intravesical chemotherapy (mitomycin C or gemcitabine) within 24 hours of TURBT — reduces recurrence
Painless gross hematuria in an adult >35-40 years requires evaluation with cystoscopy and upper tract imaging — even if it resolves.
Smoking is the single greatest risk factor; counsel cessation as part of treatment (improves outcomes).
BCG is a live attenuated tuberculosis vaccine that activates local immune response; works for high-risk NMIBC and CIS but not muscle-invasive disease.
Schistosoma haematobium causes squamous cell bladder cancer in endemic areas (Egypt, Sub-Saharan Africa).
Field cancerization: urothelial carcinoma can arise anywhere in the urothelium — always evaluate upper tract (renal pelvis, ureters) in addition to bladder.
Microscopic hematuria evaluation per AUA: CT urography + cystoscopy if risk factors (smoking, age, occupational exposure); risk-stratified approach for low-risk patients.
References
AUA/SUO 2020 — Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline (Chang et al., J Urol 2020)
AUA/ASCO/ASTRO/SUO 2017 — Treatment of Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline
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