Muscle Invasive and Metastatic Bladder Cancer Clinical Practice Guidelines (EAU, 2020)

European Association of Urology

This is a quick summary of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

May 12, 2020

The guideline on clinical management of muscle-invasive and metastatic bladder cancer was released on April 29, 2020 by the European Association of Urology.[1]

Diagnostic Evaluation

In patients with confirmed muscle-invasive bladder cancer, use computed tomography (CT) of the chest, abdomen, and pelvis as the optimal form of staging.

For upper tract evaluation and for staging, perform CT urography; use diagnostic ureteroscopy and biopsy only in cases where additional information will impact treatment decisions.

Use magnetic resonance urography when CT urography is contraindicated for reasons related to contrast administration or radiation dose.

Use CT or magnetic resonance imaging (MRI) for staging locally advanced or metastatic disease in patients in whom radical treatment is considered.

Use CT to diagnose pulmonary metastases. CT and MRI are generally equivalent for diagnosing local disease and distant metastases in the abdomen.

Treatment

Base the decision on bladder-sparing treatment or radical cystectomy in elderly/frail patients with invasive bladder cancer on tumor stage and comorbidity.

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

Treatment failure

Discuss immediate radical treatment (radical cystectomy) with patients at the highest risk of tumor progression (ie, high grade, multifocality, carcinoma in situ, tumor size).

Offer radical cystectomy to patients with tumors that are unresponsive to bacillus Calmette-Guérin (BCG) therapy.

In patients with BCG-unresponsive tumors who are not candidates for radical cystectomy due to comorbidities, offer preservation strategies (intravesical chemotherapy, chemotherapy and microwave-induced hyperthermia, electromotive administration of chemotherapy, intravesical- or systemic immunotherapy; preferably within clinical trials).

Neoadjuvant therapy

Offer neoadjuvant chemotherapy for T2-T4a, cN0M0 bladder cancer.

Always use a cisplatin-based combination regimen for neoadjuvant chemotherapy. 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 preoperative radiotherapy (RT) for operable MIBC since it will only result in down-staging, but will not improve survival.

Do not offer preoperative RT when subsequent radical cystectomy with urinary diversion is planned.

Radical cystectomy

Do not offer sexual-function–preserving radical cystectomy to men as standard therapy for muscle-invasive bladder cancer.

Offer sexual-function–preserving techniques to men motivated to preserve their sexual function, since the majority will benefit.

Select male patients based on organ-confined disease, with absence of any kind of tumor at the level of the prostate, prostatic urethra, or bladder neck.

Do not offer pelvic organ–preserving radical cystectomy to women as standard therapy for muscle-invasive bladder cancer. Select female patients based on organ-confined disease, with absence of tumor in bladder neck or urethra.

Do not delay radical cystectomy for > 3 months, as that increases the risk of progression and cancer-specific mortality.

In hospitals where radical cystectomy is offered, at least 10, and preferably > 20, of the procedures should be performed annually. 

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

Preoperative bowel preparation is not mandatory. "Fast track" measurements may reduce the time to bowel recovery.

Offer radical cystectomy in T2-T4a, N0M0, and high-risk non-muscle-invasive bladder cancer.

Perform a lymph node dissection as an integral part of radical cystectomy.           

Do not preserve the urethra if margins are positive.

Offer pharmacological prophylaxis, such as low molecular weight heparin, to patients who have undergone radical cystectomy, starting the first day post-surgery, for a period of 4 weeks.

 Palliative cystectomy

Offer radical cystectomy as a palliative treatment to patients with inoperable locally advanced tumors (T4b).

Offer palliative cystectomy to patients with symptoms.

Bladder-sparing treatments for localized disease

Offer surgical intervention or multimodality treatments (MMT) as primary curative therapeutic approaches for localized bladder cancer.

Offer MMT as an alternative to selected well-informed and compliant patients, especially those for whom radical cystectomy is not an option.

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

Do not offer radiotherapy or chemotherapy alone as primary therapy for localized bladder cancer.

Adjuvant therapy

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

Only offer immunotherapy with a checkpoint inhibitor in a clinical trial setting.

Metastatic disease

First-line treatment for cisplatin-eligible patients is with one of the following cisplatin-containing combination chemotherapy regimens:

  • GC (gemcitabine plus cisplatin)

  • MVAC (methotrexate, vinblastine, Adriamycin [doxorubicin], cisplatin), preferably with granulocyte colony-stimulating factor (G-CSF)

  • HD-MVAC (high-dose methotrexate, vinblastine, Adriamycin, cisplatin) with G-CSF

  • PCG (paclitaxel, cisplatin, gemcitabine)

Do not offer carboplatin and non-platinum combination chemotherapy.

First-line treatment in patients ineligible (unfit) for cisplatin whose tumors are programmed death ligand 1 (PD-L1)–positive is with the checkpoint inhibitors pembrolizumab or atezolizumab.

Offer carboplatin combination chemotherapy if PD-L1 is negative.

Offer pembrolizumab to patients progressing during or after platinum-based combination chemotherapy for metastatic disease. Alternatively, offer treatment within a clinical trial setting.

Offer zoledronic acid or denosumab for supportive treatment in case of bone metastases.

Offer vinflunine as subsequent-line treatment only if immunotherapy, combination chemotherapy, fibroblast growth factor receptor 3 (FGFR3) inhibitor therapy, or inclusion in a clinical trial is not feasible.

Recurrent disease

Recommendations vary by recurrence site, as follows:

  • Local - Offer radiotherapy, chemotherapy, and possibly surgery as options for treatment, either alone or in combination.

  • Distant - Offer chemotherapy as the first option, and consider metastasectomy in case of unique metastasis site.

  • Upper urinary tract – Treat as per guidelines on upper urinary tract urothelial carcinomas.

Secondary urethral tumor should be staged and treated as for primary urethral tumors.

For more information, see Bladder Cancer. For more Clinical Practice Guidelines, please go to Guidelines.

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