# Muscle-invasive and advanced bladder cancer

Source: https://onco.cc/cancers/muscle-invasive-bladder-cancer/  
OnCo record `muscle-invasive-bladder-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Once bladder cancer has grown into the muscle it needs more than scraping out: chemotherapy then removal of the bladder, or chemoradiation to keep it. For cancer that has spread, the antibody-drug conjugate enfortumab vedotin with pembrolizumab has replaced platinum chemotherapy as the first treatment.

## Summary

Muscle-invasive urothelial carcinoma is treated with cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and urinary diversion, or by trimodality bladder preservation (maximal resection plus chemoradiation) in suitable patients. Perioperative immunotherapy has entered practice: adjuvant nivolumab after cystectomy (CheckMate 274) and durvalumab with neoadjuvant chemotherapy and after surgery (NIAGARA), which improved overall survival. For metastatic disease, enfortumab vedotin with pembrolizumab nearly doubled survival compared with platinum chemotherapy (EV-302) and became the standard first-line treatment in 2023; erdafitinib is used for FGFR3-altered tumours, and platinum chemotherapy followed by avelumab maintenance remains an option. Molecular subtypes (luminal, basal) and circulating tumour DNA are being used to select who needs adjuvant treatment.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: MIBC; Invasive urothelial carcinoma; Metastatic urothelial carcinoma
- Tags: subtype-page
- Group: genitourinary
- Burden: About a quarter of bladder cancers at diagnosis plus those that progress from superficial disease; half of patients with muscle invasion die of it within five years despite surgery, and metastatic disease had a median survival near a year until antibody-drug conjugates and immunotherapy changed it.
- Subtypes: Muscle-invasive, organ-confined (T2); Locally advanced (T3 to T4, node-positive); Metastatic urothelial carcinoma; FGFR3-altered urothelial carcinoma; Variant histologies (squamous, small cell, plasmacytoid, micropapillary)
- Biomarkers: Cisplatin eligibility (kidney function, hearing, performance status); PD-L1 expression (selects immunotherapy in some settings); FGFR3 mutations and fusions (erdafitinib); Nectin-4 expression (near universal; enfortumab vedotin target); Circulating tumour DNA after cystectomy (adjuvant selection)

## Standard of care

- Muscle-invasive, cisplatin-eligible: Neoadjuvant cisplatin-based chemotherapy (dose-dense MVAC or gemcitabine-cisplatin) with durvalumab (NIAGARA), then radical cystectomy with lymph node dissection and adjuvant durvalumab; adjuvant nivolumab for high-risk residual disease (CheckMate 274). ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [NIAGARA](https://onco.cc/trials/niagara/), [Radical cystectomy](https://onco.cc/terms/cystectomy/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [CheckMate 274](https://onco.cc/trials/checkmate-274/))
- Bladder preservation: Maximal transurethral resection followed by chemoradiation, with salvage cystectomy for recurrence, in patients with unifocal tumours and no carcinoma in situ or in those unfit for surgery. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Radiosensitisers](https://onco.cc/technologies/radiosensitisers/), [Cisplatin](https://onco.cc/drugs/cisplatin/))
- Metastatic, first line: Enfortumab vedotin plus pembrolizumab (EV-302); gemcitabine-platinum followed by avelumab maintenance where the combination is unavailable. ([Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/))
- Later lines: Erdafitinib for FGFR3 alterations; platinum chemotherapy or enfortumab vedotin if not given first line; clinical trials. ([Erdafitinib](https://onco.cc/drugs/erdafitinib/), [FGFR3](https://onco.cc/targets/fgfr3-receptor/), [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/))

## State of the art

- EV-302 was the first trial in forty years to beat platinum chemotherapy first line, and it did so by a wide margin.
- Perioperative immunotherapy now improves survival around cystectomy, and circulating tumour DNA promises to select who needs it.
- Bladder preservation with chemoradiation gives survival similar to cystectomy in selected patients and is under-used.

## Open problems

- Cisplatin-ineligible patients still have fewer options.
- Choosing between cystectomy and bladder preservation lacks randomised evidence.
- Variant histologies are excluded from most trials.
- Cost and access to antibody-drug conjugates.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Bladder_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Bladder_cancer

## Connected records

- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Erdafitinib](https://onco.cc/drugs/erdafitinib/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [CheckMate 274](https://onco.cc/trials/checkmate-274/), [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/), [NIAGARA](https://onco.cc/trials/niagara/)
- terms: [Radical cystectomy](https://onco.cc/terms/cystectomy/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Radiosensitisers](https://onco.cc/technologies/radiosensitisers/)
- targets: [FGFR3](https://onco.cc/targets/fgfr3-receptor/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/)

---
JSON: https://onco.cc/api/v1/entities/muscle-invasive-bladder-cancer.json