Muscle-Invasive and Metastatic Bladder Cancer
Based on 2023 guidelines from the European Association of Urology.
Managing Risk
Inform workers in potentially hazardous workplaces of the potential carcinogenic effects
of a number of recognised substances, including duration of exposure and latency periods. Protective measures are recommended.
Pathology
Record the depth of invasion for the entire specimen (categories pT2a and pT2b, pT3a and pT3b or pT4a and pT4b).
Record margins with special attention paid to the radial margin, prostate, ureter, urethra, peritoneal fat, uterus and vaginal vault.
Record the total number of lymph nodes (LNs), the number of positive LNs, and extranodal spread.
Record the sampling sites as well as information on tumor size when providing specimens to the pathologist.
Take a biopsy of the prostatic urethra in cases of bladder neck tumor, when bladder carcinoma in situ is present or suspected, when there is positive cytology without evidence of tumor 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.
Management
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 tumor 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.
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 cisplatin-containing combination chemotherapy to patients who are ineligible for cisplatin-based combination chemotherapy.
Do not offer pre-operative radiotherapy (RT) for operable muscle-invasive bladder cancer since it will not improve survival.
Adjuvant RT can be offered following RC (pT3b-4 or positive nodes or positive margins) to improve loco-regional relapse free survival, but not overall survival.
Only offer sexual-preserving techniques to eligible men who are highly motivated to preserve their sexual function.
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.
Offer radical cystectomy (RC) to patients with T2-T4a, N0M0 disease or very high-risk nonmuscle-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 standard LND, as an extended LND does not improve survival and increases the risk of morbidity.
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 tumor in the urethra or at the level of urethral dissection.
Offer radical cystectomy as a palliative treatment to patients with locally-advanced tumors (T4b).
Offer palliative cystectomy to patients with symptoms if control is not possible by less invasive methods.
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 multidisciplinary team setting. The choice of treatment modality should be made through a shared-decision making process.
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.
Offer platinum-containing combination chemotherapy (cisplatin or carboplatin plus gemcitabine).
If actionable fibroblast growth factor receptor (FGFR) alterations: offer erdafitinib.
Consider antibody drug conjugate Trastuzumab deruxtecan in case of HER2 over expression (IHC 3+).
General statement: Offer treatment in clinical trials. Consider best supportive care alone if patient is not a candidate for further cancer-specific systemic therapy.
Follow-up
Use validated questionnaires to assess health-related quality of life in patients with muscle invasive bladder cancer, both at baseline and post-treatment.
See EAU Guidelines on Upper Urinary Tract Urothelial Carcinomas.
See EAU Guidelines on Primary Urethral Carcinoma.
How strong is the EAU's recommendation?