EAU 2025 Guidelines: Muscle-invasive and Metastatic Bladder Cancer

What This Guideline Covers

The EAU 2025 Muscle-invasive and Metastatic Bladder Cancer guideline provides evidence-based recommendations across 14 topic areas. The key (Strong-rated) recommendations are summarised below; the complete recommendation tables — including Weak recommendations with their strength ratings — plus classification and evidence tables are in the Full Guidelines tab.

Key Recommendations at a Glance

Every Strong-rated EAU recommendation. Where the guideline labels its sections, they are used as sub-headings.

Assessment of tumour specimens

• Record the depth of invasion for the entire specimen (categories pT2a and pT2b, pT3a and pT3b or pT4a and pT4b).

Primary assessment of presumably invasive bladder tumours*

• Describe all macroscopic features of the tumour (site, size, number and appearance) and mucosal abnormalities during cystoscopy. Use a bladder diagram.

• Take a biopsy of the prostatic urethra in cases of bladder neck tumour, when bladder carcinoma in situ is present or suspected, when there is positive cytology without evidence of tumour in the bladder, or when abnormalities of the prostatic urethra are visible.

• In men with a negative prostatic urethral biopsy undergoing subsequent orthotopic neobladder construction, an intra- operative frozen section can be omitted.

• In men with a prior positive transurethral prostatic biopsy, subsequent orthotopic neobladder construction should not be denied a priori, unless an intra-operative frozen section of the distal urethral stump reveals malignancy at the level of urethral dissection.

• In women undergoing subsequent orthotopic neobladder construction, obtain procedural information (including histological evaluation) of the bladder neck and urethral margin, either prior to, or at the time of cystoscopy.

• In the pathology report, specify the grade, depth of tumour invasion, and whether the lamina propria and muscle tissue are present in the specimen.

• If an MRI is performed for local staging of bladder cancer it should be done before TURBT.

• In patients with confirmed muscle- invasive bladder cancer, use computed tomography (CT) of the chest, abdomen and pelvis for staging, including some form of CT urography with designated phases for optimal urothelial evaluation.

• Use CT urography, unless it is contraindicated for reasons related to contrast administration or radiation dose; in that case use MRI.

• Base the decision on bladder-sparing treatment or radical cystectomy in older/ frail patients with invasive bladder cancer on tumour stage and frailty.

• Assess comorbidity by a validated score, such as the Charlson Comorbidity Index. The American Society of Anesthesiologists score should not be used in this setting.

• Use susceptible FGFR3 alterations to select patients with unresectable or metastatic urothelial carcinoma for treatment with erdafitinib

• If eligible for cisplatin-based chemotherapy, offer neoadjuvant cisplatin-based combination chemotherapy to patients with muscle- invasive bladder cancer (T2–T4a, cN0 M0).

• Do not offer neoadjuvant chemotherapy to patients who are ineligible for cisplatin- based combination chemotherapy.

• Only offer neoadjuvant immunotherapy to patients within a clinical trial setting.

• Do not offer pre-operative radiotherapy (RT) for operable muscle-invasive bladder cancer since it will not improve survival.

• Offer radical cystectomy (RC) to patients with T2–T4a, N0M0 disease or very high- risk non-muscle-invasive bladder cancer.

• Do not delay RC for > 3 months as it increases the risk of progression and cancer-specific mortality, unless the patient receives neoadjuvant chemotherapy.

• Perform a lymph node dissection as an integral part of RC.

• Perform a standard LND, as an extended LND does not improve survival and increases the risk of morbidity.

• Perform at least 20 RCs per hospital/per year.

• Before RC, fully inform the patient about the benefits and potential risks of all possible alternatives. The final decision should be based on a balanced discussion between the patient and the surgeon.

• Do not offer an orthotopic bladder substitute diversion to patients who have an invasive tumour in the urethra or at the level of urethral dissection.

• Do not offer pre-operative bowel preparation.

• Employ ‘Fast track’ measurements to reduce the time to bowel recovery.

• Offer pharmacological VTE prophylaxis, such as low-molecular-weight heparin to RC patients, starting the first day post- surgery, for a period of at least four weeks.

• Only offer sexual-preserving techniques to eligible men who are highly motivated to preserve their sexual function.

• Select men for sexual-preserving techniques based on: • organ-confined disease; • absence of any kind of malignancy at the level of the prostate, prostatic urethra or bladder neck.

• Perform sexual organ-preserving techniques in eligible women. Select patients based on absence of tumour in the area to be preserved to avoid positive soft tissue margins.

• Inform the patient of the advantages and disadvantages of open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) to allow selection of the proper procedure.

• Select experienced centres, not specific techniques, both for RARC and ORC.

• Do not offer transurethral resection of bladder tumour alone as a curative treatment option as most patients will not benefit.

• Do not offer radiotherapy alone as primary therapy for localised bladder cancer.

• Do not offer chemotherapy alone as primary therapy for localised bladder cancer.

• Offer radical cystectomy or trimodality bladder-preserving treatments (TMT) as primary curative option for eligible patients since they are more effective than radiotherapy alone.

• Manage all patients who are candidates for TMT in a mutlidisciplinary team setting. The choice of treatment modality should be made through a shared- decision making process.

• Advise patients who are candidates for TMT that life-long bladder monitoring is essential.

• Offer adjuvant cisplatin-based combination chemotherapy to patients with pT3/4 and/or pN+ disease if no neoadjuvant chemotherapy has been given.

• Use antibody drug conjugate enfortumab vedotin (EV) in combination with checkpoint inhibitor (CPI) pembrolizumab.

• If contraindications for EV or EV not available: Offer platinum-containing combination chemotherapy (cisplatin or carboplatin plus gemcitabine) followed by maintenance treatment with CPI avelumab in patients with at least stable disease on chemotherapy.

• If contraindications for EV (or EV not available) and cisplatin-eligible: Consider cisplatin/gemcitabine in combination with CPI nivolumab.

• If contraindications for EV and checkpoint inhibitor therapy: Use platinum-containing combination chemotherapy (cisplatin or carboplatin plus gemcitabine).

• Offer antibody drug conjugate enfortumab vedotin.

• If actionable FGFR alterations and prior CPI: offer erdafitinib.

• If no prior CPI: offer pembrolizumab.

• General statement: Offer treatment in clinical trials. Consider best supportive care alone if a patient is not a candidate for further cancer-specific systemic therapy.

• Use validated questionnaires to assess health-related quality of life in patients with MIBC, both at baseline and post- treatment.

• Discuss the type of urinary diversion taking into account patient preference, existing comorbidities, tumour variables and coping abilities.