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3Bladder / Urothelial

Snapshot. Depth decides everything: NMIBC (non-muscle-invasive) vs MIBC (≥T2) vs metastatic. ~90% urothelial. Cisplatin fitness is the second gate.
⚠ Small-cell / neuroendocrine variant (<1%, often mixed): even a MINOR small-cell component dictates SCLC-type chemo (platinum + etoposide) — it drives the prognosis.
Workup
Cystoscopy + urine cytology · CT urogram (whole tract — field disease) · TURBT — must contain DETRUSOR MUSCLE, re-resect if absent in high-grade/T1 (one act, two jobs: gives the depth AND treats NMIBC) · CT chest/abdo/pelvis ± MRI pelvis if muscle-invasive · cisplatin fitness: CrCl ≥60, ECOG 0–1, no significant hearing loss/neuropathy/heart failure · FGFR + PD-L1 if metastatic.
Treatment by setting
SettingTreatment
NMIBC — Ta / T1 / CIS
no muscle invasion (~75%)
The TURBT has already treated it
Then intravesical BCG for high-risk, or intravesical chemo
BCG-unresponsive → pembrolizumab · nadofaragene · cystectomy
MIBC — cisplatin-FIT
≥T2, no mets, CrCl ≥60
Neoadjuvant chemo-IO → RADICAL CYSTECTOMY + PLND → adjuvant IO
Standard: durvalumab + gem/cis ×4 → cystectomy → durvalumab ×8 cycles (NIAGARA)
⚠ The adjuvant course is FINITE — 8 cycles, then STOP not "until progression"
Alternative adjuvant if high-risk post-op → nivolumab ×1 yr (CheckMate-274)
MIBC — cisplatin-UNFIT
CrCl <60 · ECOG ≥2 · neuropathy · hearing loss · HF
Perioperative EV + pembrolizumab — 3 neoadjuvant cycles → CYSTECTOMY + PLND → adjuvant pembrolizumab (EV-303 / KEYNOTE-905) pCR 57% vs 9%; OS not reached vs 41.7 mo · carboplatin is NOT an adequate substitute — this replaced it
⚠ No bladder-preservation arm — the benefit was earned WITH cystectomy
Truly unfit for surgery → trimodality / RT
MIBC — BLADDER PRESERVATION
refuses/unfit for cystectomy, or favourable: solitary, <5 cm, fully resected at TURBT, no hydronephrosis, no extensive CIS
TRIMODALITY THERAPY = ① maximal TURBT → ② radiotherapy → ③ concurrent radiosensitiser cisplatin · 5-FU + mitomycin (BC2001) · gemcitabine if cisplatin-unfit
⚠ Non-negotiable: LIFELONG cystoscopy — the bladder is still there salvage cystectomy is the bail-out
⚠ Adjuvant IO after TMT is NOT established all the evidence ((NIAGARA) (CheckMate-274)) is post-CYSTECTOMY; the trials built for this question ((S1806) (KEYNOTE-992)) have not reported. If given anyway, every framework is finite, ~6–8 months
ctDNA to SELECT rather than treat blindly (IMvigor011) see ctDNA in Tools · ⚠ ctDNA does NOT survey the bladder — cystoscopy stays independent
METASTATIC
1st line → EV + pembrolizumab (EV-302) enfortumab vedotin, a Nectin-4 ADC — replaced platinum chemo
Alternative → platinum + gemcitabine → avelumab maintenance (JAVELIN Bladder 100)
FGFR-altered → erdafitinib
Watch
EV → hyperglycaemia/DKA · peripheral neuropathy · severe skin (SJS/TEN) — check glucose and skin before every dose. Cisplatin → nephro/oto/neurotoxicity. BCG → cystitis, rarely disseminated BCG infection.
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