This site is for healthcare professionals.

Current treatments and considerations in MIBC

Recommendations from the ESMO Clinical Practice Guidelines, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), and EAU Guidelines

Leading guidelines recommend radical cystectomy with appropriate systemic therapy as the primary treatment option for eligible patients with MIBC.1,3

Surgical treatments

Radical cystectomy with PLND

Radical cystectomy with PLND is recommended in patients with MIBC without node involvement or metastasis. However, surgery typically involves removal of the bladder but often also the entire urethra and adjacent organs, such as the uterus and vagina in women and the prostate and seminal vesicles in men, which can result in sexual and urinary complications.1

Partial cystectomy

Partial cystectomy is recommended in select patients when an invasive bladder tumour can be removed while preserving bladder function and capacity. It is not a standard surgical treatment for MIBC due to inconsistent outcomes and is not considered appropriate for stage III disease.1

Bladder Sparing

Bladder-sparing approaches—including TURBT, chemotherapy, and radiotherapy—are supported by guidelines in certain patients with MIBC who are unfit for radical cystectomy or decline it.1,3 TMT combines TURBT, chemotherapy, and radiation therapy; however, a meta-analysis suggested that TMT approaches have inferior outcomes vs radical cystectomy.4

Systemic treatments

Perioperative therapy

Perioperative treatment approaches include systemic therapy before and following surgery. The "sandwich" approach of using systemic therapies in both the neoadjuvant and adjuvant settings has recently been introduced by the NCCN Guidelines® in their MIBC treatment recommendations1:

Step 1 Step 2 Step 3
Neoadjuvant cisplatin-based chemotherapy + immunotherapy Radical cystectomy Adjuvant immunotherapy

Considerations

  • Eligibility: Patients must be eligible for cisplatin to receive this combination of neoadjuvant chemotherapy and immunotherapy. Patients are ineligible to receive cisplatin if they meet at least one of the following criteria which are defined by Galsky et al. as a WHO or ECOG PS of ≥2 or Karnofsky performance status 60%-70%, a CrCl of <60mL/min, a hearing loss of CTCAE version 4.0 Grade ≥2, CTACE version 4.0 peripheral neuropathy Grade ≥2, or NYHA class III heart failure5
  • Carboplatin: The ESMO Clinical Practice Guidelines only recommend neoadjuvant cisplatin for MIBC and the NCCN Guidelines state that carboplatin has not demonstrated a survival benefit as an alternative to cisplatin and should not be substituted1,3
  • For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative treatment1

Neoadjuvant therapy

Recommended treatment options:

Cisplatin eligible1,3 Cisplatin ineligible1,2
Cisplatin-based combination chemotherapy No neoadjuvant therapy options supported by guidelines
Up to 40% of patients with MIBC are ineligible for cisplatin and, in the absence of neoadjuvant therapy options, can only proceed to surgery6

Considerations

  • Eligibility: Ineligible patients meet at least one of the following criteria which are defined by Galsky et al. as a WHO or ECOG PS of ≥2 or Karnofsky performance status 60%-70%, a CrCl of <60mL/min, a hearing loss of CTCAE version 4.0 Grade ≥2, CTACE version 4.0 peripheral neuropathy Grade ≥2, or NYHA class III heart failure5
  • Carboplatin: The ESMO Clinical Practice Guidelines only recommend neoadjuvant cisplatin for MIBC and the NCCN Guidelines state that carboplatin has not demonstrated a survival benefit as an alternative to cisplatin and should not be substituted1,3
  • For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative treatment1

Adjuvant therapy

Recommended treatment options:

  • Cisplatin-based chemotherapy is recommended in eligible patients with high-risk pathology (ie, pT3, pT4, or pN+ tumour) who have not received this therapy in the neoadjuvant setting, as per NCCN Guidelines and EAU Guidelines. However, the ESMO Guidelines note that while a meta-analysis showed survival benefits, adjuvant cisplatin-based chemotherapy remains an area of debate due to the lack of published positive overall survival results from a Phase III trial1,3
  • Radiotherapy in selected patients1,2

Considerations

  • Eligibility: Adjuvant therapy use depends on patient eligibility and prior neoadjuvant therapy1,3
  • Adjuvant nivolumab can be considered according to the NCCN Guidelines and the EAU Guidelines in select patients with high-risk disease (pT3, pT4, or pN+ tumor) following cystectomy who are not eligible for or declined adjuvant cisplatin-based chemotherapy. It is not, however, recommended by the ESMO Guidelines due to inconsistencies across trials and uncertainty on the relationship between DFS and OS with immunotherapy1,3
  • Adjuvant immunotherapy (ie, nivolumab) may have specific PD-L1 expression requirements for EMA approval in some regions2,7,8
  • Prognostic tools: There is a lack of tools to identify surgically treated patients at risk for disease progression9

Approximately 50% of patients with MIBC progress to metastatic disease within 3 years10

aggressive-disease

What makes MIBC an aggressive disease?

current-treatment-options-and-limitations

What are the current treatment options and considerations for MIBC?

collaborative-approach-essential

Why is a collaborative approach essential in the treatment of MIBC?

*Cisplatin ineligibility criteria defined by Galsky et al. include a WHO or ECOG PS of ≥2 or Karnofsky performance status 60%-70%, a CrCl of <60 mL/min, a hearing loss of CTCAE version 4.0 Grade ≥2, CTACE version 4.0 peripheral neuropathy Grade ≥2, or NYHA class III heart failure.4

CrCl – creatinine clearance; CTCAE – Common Terminology Criteria for Adverse Events; ECOG PS – Eastern Cooperative Oncology Group performance status; ESMO – European Society for Medical Oncology; MIBC – muscle-invasive bladder cancer; NCCN – National Comprehensive Cancer Network; PD-L1 – programmed death-ligand 1; PLND – pelvic lymph node dissection; TURBT – Transurethral resection of bladder tumour; TMT – trimodality therapy; WHO – World Health Organization.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed September 25, 2025. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Witjes JA, Bruins HM, Carrión A, et al. EAU Guidelines on muscle-invasive and metastatic bladder cancer. Published March 2025. Accessed 26 September 2025. https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer. 3. Powles T, Bellmunt J, Compérat E, at al. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022;33(3):244-58. 4. Ding H, Fan N, Ning Z, et al. Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: a meta-analysis. Front Oncol 2020:10:564779. 5. Jiang D, Sridhar S. De ning cisplatin eligibility in patients with muscle-invasive bladder cancer - beyond the abstract. UroToday. 14 April 2021. Accessed 15 March 2025. https://www.urotoday.com/recent-abstracts/urologic-oncology/bladder-cancer/129020-de ning-cisplatin-eligibility-inpatients-with-muscle-invasive-bladder-cancer-beyond-the-abstract.html. 6. Powles T, Drakaki A, Teoh J, et al. J Clin Oncol 2022;40(suppl 6):TPS579. 7. Bristol Myers Squibb Immunotherapy Summary of Product Characteristics. 8. Immunotherapy [package insert]. Princeton, NJ: Bristol Myers Squibb. 9. Flammia RS, Tuderti G, Bologna E, et al. J Clin Med 2024;13(18):5466. 10. Tian J, Sun J, Fu G, et al. Population-based outcome of muscle-invasive bladder cancer following radical cystectomy: who can benefit from adjuvant chemotherapy? Transl Androl Urol 2021;10(1):356-73.