- Bladder cancer M:F incidence ratio ≈3:1; median age at diagnosis is 70; the disease is more common in Caucasian Americans.
- Smoking is the most common risk factor (responsible for 30–50% of cases in males); occupational exposure to aromatic amines (especially β-naphthylamine) is second most common.
- Cyclophosphamide is the only chemotherapeutic agent proven to cause bladder cancer; chronic Schistosoma haematobium infection is associated with squamous cell carcinoma of the bladder.
- ≈90% of bladder cancers are urothelial carcinoma; ≈75–80% present as non–muscle-invasive bladder cancer (NMIBC), ≈20–25% as muscle-invasive (MIBC).
- Of NMIBC: ≈70% Ta, ≈20% T1, ≈10% CIS. T1 lesions are almost always high-grade.
- AJCC 8th ed. T-staging key cut-offs: pTa non-invasive papillary, pTis CIS, pT1 invades lamina propria, pT2a/b superficial/deep muscularis propria, pT3a/b microscopic/macroscopic perivesical fat, pT4a invades prostatic stroma/seminal vesicles/uterus/vagina, pT4b invades pelvic/abdominal wall.
- Painless gross hematuria is the most common presentation; ≈85% present with gross hematuria. Any episode of gross hematuria warrants evaluation.
- Urine cytology is highly specific (~85%) but has poor sensitivity (~50%); sensitivity is higher in high-grade disease (~84%) than low-grade (~16%).
- AUA microscopic hematuria risk stratification guides workup: low-risk patients can have cystoscopy + US (or repeat UA); intermediate-risk require US + cystoscopy; high-risk require CT urography + cystoscopy.
- Aggressive variant histologies—micropapillary, plasmacytoid, sarcomatoid, and nested—warrant consideration of upfront cystectomy.
- Repeat TURBT is recommended for all T1 disease and when initial TURBT was incomplete or muscularis propria was absent.
- Immediate post-TURBT intravesical chemotherapy (gemcitabine or MMC) reduces recurrence (NNT ≈8) but does not reduce progression; supported by SWOG 0337.
- BCG induction + maintenance (SWOG 8507) is the only intravesical therapy shown to reduce both recurrence and progression in NMIBC.
- BCG-unresponsive disease (BCG-refractory or relapse within 6 months / CIS within 12 months) is best treated with radical cystectomy; alternatives in unfit patients include pembrolizumab, nadofaragene firadenovec, oportuzumab monatox, or BCG + N-803.
- Neoadjuvant cisplatin-based chemotherapy (gemcitabine-cisplatin, MVAC, or dd-MVAC) before radical cystectomy improves overall survival (~5% absolute benefit at 5 years; SWOG 8710, BA06 30894).
- Cisplatin ineligibility criteria (CUA mnemonic HE 2 NICE): ≥grade 2 Hearing loss, eGFR ≤50, ≥grade 2 Neuropathy, untreated Infection, Cardiac failure NYHA >2, ECOG ≥2.
- Adjuvant nivolumab (CheckMate 274) improves disease-free survival in high-risk patients after radical cystectomy.
- Standard radical cystectomy in males includes bladder, prostate, and seminal vesicles; in females includes bladder, ovaries, fallopian tubes, uterus/cervix, and anterior vagina (with increasing emphasis on organ preservation).
- Bilateral pelvic lymphadenectomy is mandatory at any curative-intent surgery; minimum is external iliac, internal iliac, and obturator nodes with >12 nodes evaluated; SWOG S1011 and LEA AUO AB 25/02 show no benefit to extended over standard PLND.
- Trimodal bladder-preserving therapy = maximal TURBT + concurrent chemoradiation; ideal candidates have unifocal, no CIS, no hydronephrosis, and a tumor that can be completely transurethrally resected.
- Urethrectomy indications: positive urethral margin; in males with high-grade or invasive urethral disease distal to prostatic urethra or suspected prostatic stromal involvement; in females with bladder neck tumors.
- Contraindications to continent urinary diversion: insufficient bowel length, inability/unwillingness to self-catheterize, eGFR <45 mL/min, hepatic dysfunction, cancer at urethral margin (for neobladder), and severe uncorrectable urethral stricture.
- Metabolic complications of urinary diversion (mnemonic LSD ORGASMIC): Lytes (hyperchloremic metabolic acidosis with ileal/colon conduit; hypochloremic hyperkalemic acidosis with jejunal; hypochloremic hypokalemic alkalosis with stomach), Sensorium altered, Drug metabolism, Osteomalacia, Renal function decline, Growth retardation, Acidosis/Alkalosis, Stones, Malabsorption (B12, bile salts, fat), Infections, Cancer (especially adenocarcinoma).
- Wallace ureteroileal anastomosis has the lowest complication rate; avoid in patients with extensive CIS or high recurrence risk in the ureter.
- The first-line systemic therapy for metastatic urothelial carcinoma is 4–6 cycles of gemcitabine + cisplatin (or gemcitabine + carboplatin if cisplatin-ineligible); pembrolizumab is preferred second-line after platinum-based chemotherapy (KEYNOTE-045).
- For locally advanced unresectable disease (cT4b and/or cN1–3), curative multimodality treatment can still be offered; persistent N3 or non-downstaged cT4b favours consolidative radiotherapy over surgery.
- Squamous cell carcinoma of the bladder is more common in women, spinal-cord-injury patients, chronic inflammation, and Schistosoma-endemic regions; presents at advanced stage.
- Adenocarcinoma of the bladder is most often metastatic from another primary; primary adenocarcinoma risk factors include nonfunctioning bladder, obstruction, chronic irritation, and bladder exstrophy.
- Small cell carcinoma of the bladder should be managed as metastatic disease (initial chemotherapy followed by radiation or cystectomy as consolidation) even when localised; mixed urothelial tumors with any small cell component are treated as small cell.