Bladder cancer is the sixth most common cancer in the United States, with approximately 83,000 new cases and 17,000 deaths estimated annually by the American Cancer Society. It is roughly four times more common in men than women and is most frequently diagnosed in adults over age 55. The most common type, urothelial carcinoma (also called transitional cell carcinoma), accounts for about 90% of bladder cancers in the U.S.
The hallmark of bladder cancer management is the distinction between non-muscle-invasive disease (confined to the inner lining) and muscle-invasive disease (penetrating into or through the bladder wall muscle). This distinction fundamentally determines the treatment approach and prognosis.
What Is Bladder Cancer?
The bladder is a hollow, muscular organ in the pelvis that stores urine produced by the kidneys. Its inner lining is composed of urothelial cells (transitional epithelium) that can stretch as the bladder fills. Bladder cancer most commonly arises from these urothelial cells.
The most common presenting symptom is hematuria—blood in the urine. This may be visible (gross hematuria, often painless) or detected only by laboratory testing (microscopic hematuria). Other symptoms can include frequent urination, urgency, painful urination (dysuria), and pelvic pain. Any unexplained hematuria warrants prompt evaluation.
Types of Bladder Cancer
- Urothelial carcinoma (transitional cell carcinoma) — About 90% of bladder cancers. Can be low-grade (slow-growing, less likely to invade) or high-grade (aggressive, more likely to invade and metastasize).
- Squamous cell carcinoma — About 4% of U.S. bladder cancers (more common in regions with endemic schistosomiasis). Associated with chronic irritation and infection.
- Adenocarcinoma — About 2% of bladder cancers. Arises from glandular cells; may be associated with urachal remnants.
- Small cell carcinoma — Rare and aggressive. Treated similarly to small cell lung cancer with platinum-based chemotherapy.
Risk Factors
- Smoking — The single greatest risk factor, accounting for approximately 50% of bladder cancers. Smokers are three to four times more likely to develop bladder cancer than non-smokers. Carcinogens from cigarette smoke are filtered by the kidneys and concentrated in the urine, directly exposing the bladder lining.
- Occupational chemical exposure — Workers exposed to aromatic amines, polycyclic aromatic hydrocarbons, and certain dyes (in industries such as rubber, textiles, paint, and leather) face increased risk.
- Age and sex — Median age at diagnosis is 73. Men are affected roughly four times more often than women.
- Prior radiation or chemotherapy — Pelvic radiation and cyclophosphamide (an alkylating agent) increase risk.
- Chronic bladder irritation — Recurrent UTIs, long-term catheterization, and bladder stones are associated with squamous cell carcinoma.
- Arsenic exposure — High concentrations of arsenic in drinking water increase risk.
- Family history and genetics — Lynch syndrome and other inherited conditions can increase bladder cancer risk.
Bladder Cancer Staging
| Stage | Description | Classification | 5-Year Survival |
|---|---|---|---|
| Stage 0a (Ta) | Non-invasive papillary carcinoma confined to the urothelium | Non-muscle-invasive | ~96% |
| Stage 0is (Tis) | Carcinoma in situ (CIS); flat, high-grade cancer confined to the urothelium | Non-muscle-invasive | ~96% |
| Stage I (T1) | Cancer has invaded the lamina propria (subepithelial connective tissue) but not the muscle | Non-muscle-invasive | ~88% |
| Stage II (T2) | Cancer has invaded the muscularis propria (detrusor muscle) | Muscle-invasive | ~63% |
| Stage III (T3–T4a) | Cancer extends through the muscle into perivesical fat or invades adjacent organs (prostate, uterus, vagina) | Muscle-invasive | ~46% |
| Stage IV | Cancer invades the pelvic or abdominal wall, or has spread to lymph nodes or distant organs | Metastatic | ~15% |
Survival rates from SEER data. Individual outcomes vary based on grade, molecular features, and treatment response.
Treatment for Non-Muscle-Invasive Bladder Cancer (NMIBC)
Transurethral Resection of Bladder Tumor (TURBT)
TURBT is the initial treatment and diagnostic procedure for bladder cancer. Using a cystoscope inserted through the urethra, the surgeon resects all visible tumor from the bladder wall and obtains tissue for pathological analysis. A second "re-staging" TURBT may be performed 2–6 weeks later for high-grade tumors or T1 disease to ensure complete resection and accurate staging.
Intravesical Therapy
Medications instilled directly into the bladder after TURBT reduce the risk of recurrence and progression:
BCG (Bacillus Calmette-Guerin) Immunotherapy
BCG is the gold standard intravesical therapy for intermediate- and high-risk NMIBC. It uses a weakened form of the tuberculosis bacterium to stimulate the immune system to attack cancer cells in the bladder lining. The treatment protocol typically includes:
- Induction course: Weekly BCG instillations for 6 weeks, starting 2–4 weeks after TURBT.
- Maintenance therapy: The SWOG protocol involves 3 weekly instillations at 3, 6, 12, 18, 24, 30, and 36 months. Maintenance BCG has been shown to reduce recurrence by approximately 32% compared to induction alone.
Side effects include irritative voiding symptoms (frequency, urgency, dysuria), flu-like symptoms, and rarely, systemic BCG infection requiring anti-tuberculosis medication. BCG shortages have been a significant clinical challenge in recent years.
Intravesical Chemotherapy
- Mitomycin C — The most commonly used intravesical chemotherapy agent. A single post-TURBT dose reduces recurrence by approximately 39% for low-grade Ta tumors. Used as an alternative to BCG for low-risk disease or when BCG is unavailable.
- Gemcitabine — Increasingly used as an alternative intravesical agent with a favorable side effect profile.
BCG-Unresponsive Disease
When bladder cancer recurs or persists despite adequate BCG treatment, options include:
- Radical cystectomy — Remains the standard recommendation for BCG-unresponsive high-grade NMIBC.
- Pembrolizumab (Keytruda) — FDA-approved for BCG-unresponsive CIS with or without papillary tumors in patients who are ineligible for or elect not to undergo cystectomy. The KEYNOTE-057 trial showed a complete response rate of approximately 41%.
- Nadofaragene firadenovec (Adstiladrin) — An adenovirus-based gene therapy approved in 2022 for BCG-unresponsive NMIBC, delivering a copy of the interferon alfa-2b gene directly to bladder cells.
Treatment for Muscle-Invasive Bladder Cancer (MIBC)
Neoadjuvant Chemotherapy
Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. Neoadjuvant chemotherapy improves overall survival by approximately 5–8% compared to surgery alone. Standard regimens include:
- Dose-dense MVAC (ddMVAC) — Methotrexate, vinblastine, doxorubicin, and cisplatin given every two weeks with growth factor support. Preferred for its efficacy and shorter treatment duration.
- Gemcitabine/cisplatin (GC) — An alternative with a more tolerable side-effect profile.
Learn more about chemotherapy regimens.
Radical Cystectomy
Radical cystectomy is the standard surgical treatment for muscle-invasive bladder cancer. The procedure involves:
- In men: Removal of the bladder, prostate, seminal vesicles, and pelvic lymph nodes
- In women: Removal of the bladder, uterus, ovaries, fallopian tubes, anterior vaginal wall, and pelvic lymph nodes
Urinary diversion options after cystectomy include:
- Ileal conduit — A segment of small bowel connects the ureters to a stoma on the abdomen, with urine collected in an external bag. The simplest and most common diversion.
- Neobladder (orthotopic diversion) — A new bladder is constructed from intestinal tissue and connected to the urethra, allowing patients to urinate relatively normally. Requires motivation and ability to self-catheterize if needed.
- Continent cutaneous diversion — An internal pouch is created with a catheterizable stoma, avoiding an external bag.
Adjuvant Immunotherapy
Nivolumab (Opdivo) is approved as adjuvant therapy for patients with muscle-invasive urothelial carcinoma at high risk of recurrence after radical surgery, based on the CheckMate 274 trial showing improved disease-free survival. This is particularly important for patients who did not receive neoadjuvant chemotherapy.
Bladder-Preserving Approaches (Trimodal Therapy)
For select patients who wish to preserve their bladder or are not candidates for cystectomy, trimodal therapy (TMT) combines maximal TURBT, concurrent chemotherapy, and radiation therapy. Outcomes in carefully selected patients (complete TURBT, unifocal tumor, no CIS, no hydronephrosis) approach those of radical cystectomy, with the advantage of bladder preservation. However, lifelong cystoscopic surveillance is essential. Learn more about radiation therapy.
Treatment for Metastatic Bladder Cancer
Treatment for metastatic urothelial carcinoma has been revolutionized by immunotherapy and antibody-drug conjugates:
First-Line Treatment
- Cisplatin-eligible patients: Gemcitabine/cisplatin or ddMVAC followed by avelumab (Bavencio) maintenance immunotherapy, based on the JAVELIN Bladder 100 trial showing improved overall survival.
- Cisplatin-ineligible patients: Pembrolizumab or atezolizumab for patients with high PD-L1 expression; carboplatin-based chemotherapy followed by avelumab maintenance for others.
Second-Line and Beyond
- Enfortumab vedotin (Padcev) — An antibody-drug conjugate targeting Nectin-4, expressed on most urothelial cancers. Combined with pembrolizumab, it has shown unprecedented response rates in the EV-302 trial and is being studied as a potential new first-line standard.
- Sacituzumab govitecan (Trodelvy) — A Trop-2-directed antibody-drug conjugate approved for previously treated metastatic urothelial carcinoma.
- Erdafitinib (Balversa) — An FGFR inhibitor for patients with susceptible FGFR2 or FGFR3 genetic alterations (present in approximately 15–20% of advanced urothelial carcinomas).
Follow-Up and Surveillance
Bladder cancer requires rigorous long-term follow-up due to high recurrence rates. For NMIBC, surveillance typically includes cystoscopy every 3 months for the first 2 years, then at increasing intervals. Urine cytology may complement cystoscopy, particularly for detecting CIS. For patients treated for MIBC, follow-up includes imaging of the upper urinary tract and cross-sectional body imaging to monitor for recurrence.