Mohammad Abufaraj1, Beat Foerster2, Eva Schernhammer3, Marco Moschini4, Shoji Kimura5, Melanie R Hassler6, Mark A Preston7, Pierre I Karakiewicz8, Mesut Remzi6, Shahrokh F Shariat9. 1. Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. 2. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Kantonsspital Winterthur, Winterthur, Switzerland. 3. Department of Epidemiology, Harvard T.H Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria. 4. Department of Urology, Medical University of Vienna, Vienna, Austria; Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland. 5. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan. 6. Department of Urology, Medical University of Vienna, Vienna, Austria. 7. Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 8. Department of Urology, University of Montreal, Montreal, Quebec, Canada. 9. Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA. Electronic address: sfshariat@gmail.com.
Abstract
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.
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.
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