Micropapillary Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-analysis of Disease Characteristics and Treatment Outcomes

Context: The optimal treatment of urothelial bladder cancer (UBC) with micropapillary (MP) variant histology is not clear.

Objective: To review the current literature on disease characteristics and treatment outcomes of MP UBC.

Evidence Acquisition: A systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions. The primary end points were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).

Evidence Synthesis: We identified 758 reports comprising a total of 3154 patients, of which 28 and 15 articles were selected for qualitative and quantitative analysis, respectively. In patients with T1 MP UBC, the 5-yr CSS rates for early radical cystectomy (RC) ranged from 81% to 100%, while they were between 60% and 85% for transurethral resection of the bladder and Bacillus Calmette-Guérin (BCG). In studies reporting on neoadjuvant chemotherapy (NAC), the rates of complete pathological response (ypT0) ranged from 11% to 55%. Nevertheless, the use of NAC did not improve RFS (hazard ratio [HR] 1.23, 95% confidence interval [CI] 0.52-2.93, p=0.6), CSS (HR 0.9, 95% CI 0.48-1.7, p=0.8), or OS (HR 1.35, 95% CI 0.98-1.86, p=0.1). Fifty-three percent (95% CI 43-63%) of patients who underwent RC alone had locally advanced disease (≥pT3), and 43% (95% CI 33-52%) were harbouring lymph node metastases. MP component at RC was not significantly associated with worse RFS (HR 1.25, 95% CI 0.88-1.78, p=0.2), CSS (HR 0.96, 95% CI 0.57-1.6, p=0.9), or OS (HR 1.20, 95% CI 0.88-1.62, p=0.3) when adjusted for pathological features.

Conclusions: While MP UBC is associated with clinicopathological features of advanced disease, it is not associated with worse survival outcomes in patients undergoing RC. NAC results in pathological downstaging in a significant number of patients. Nevertheless, this does not translate into better survival outcomes. The optimal treatment of patients with cT1 remains controversial.

Patient Summary: Our results suggest that micropapillary urothelial bladder cancer does not necessarily mandate different treatment algorithms. Nevertheless, each case should be discussed individually considering other clinicopathological factors.