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eUpdate – Bladder Cancer Treatment Recommendations

eUpdate – Bladder Cancer Treatment Recommendations

Published: 16 July 2020
ESMO Guidelines Committee

This eUpdate refers to the Bladder cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.


Management of advanced and metastatic disease

Text update

Chemotherapy (ChT) regimens recommendations for first-line advanced disease have not changed from the previous eUpdate.

Platinum-containing combination ChT is the standard of care for advanced or metastatic urothelial cancer (UC) [I, A] [1,2]. Gemcitabine with cisplatin or gemcitabine with carboplatin are the most widely used regimens. Six cycles of ChT is considered standard therapy.

Maintenance avelumab, in metastatic UCs which have not progressed on first-line platinum-based ChT (4-6 cycles), is associated with an overall survival (OS) advantage compared with best supportive care (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.56-0.86) [I, A] [3]. An increase in median OS from 14 to 21 months was observed with avelumab. This benefit was seen regardless of predefined subgroups of patients such as PD-L1 status, ChT regimen given and response to ChT. Treatment was started within 10 weeks of completion of ChT and given until progression of disease. The adverse event profile was consistent with that seen with immune checkpoint inhibitors in UC [4,5]. Maintenance avelumab has not yet been approved by the European Medicine Agencies (EMA).

Treatment after disease progression with first-line ChT and maintenance avelumab should follow previous guidelines for treatment refractory disease

Pembrolizumab or atezolizumab remain reasonable alternatives to first-line carboplatin-based ChT in metastatic patients who are programmed death-ligand 1 (PD-L1)-positive [III, B] [4,5].  

Recommendation: Maintenance avelumab is recommended in metastatic UCs which have not progressed on first-line platinum-based ChT (4-6 cycles) [I, A], where availablea.

Table 1. Recommendations for treatment-naive advanced or metastatic UC

 Patients characteristicsb

 Treatment recommendation

 Cisplatin eligible

 Cisplatin-based ChT [I, A] followed by maintenance avelumab for tumours which have not progressed on ChT [I, A]a

 Cisplatin ineligible and PD-L1 unknown or negative

Gemcitabine/carboplatin [II, B] followed by maintenance avelumab for tumours which have not progressed on ChT [I, A]

Cisplatin ineligible and PD-L1-positive



 Gemcitabine/carboplatin [II, B] followed by maintenance avelumab for tumours which have not progressed on ChT [I, A]a


Atezolizumab or pembrolizumab [III, B]

ChT, chemotherapy; PD-L1, programmed death-ligand 1; PS, performance status, UC, urothelial cancer.

a Not approved by EMA
b Creatinine clearance <60 ml/min or PS2 or comorbidity

Levels of evidence and grades of recommendation are presented according to the grading system used for all ESMO Clinical Practice Guidelines (adapted from the Infectious Diseases Society of America - United States Public Health Service Grading System); see Table 3 in the original text. 


  1. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18(17):3068-77.
  2. De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012;30:191-199.
  3. Powles T , Park SH,  Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma. JAVELIN Bladder 100 phase III results. J Clin Oncol 38; 2020 (suppl; abstr LBA1).
  4. Balar AV, Galsky MD, Rosenberg JE, et al. IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67-76.
  5. Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicenter, single-arm, phase 2 study. Lancet Oncol 2017;18(11):1483-92.

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