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      Micropapillary Bladder Cancer: Insights from the National Cancer Database

      research-article
      a , a , a , a , a , b , a , a , *
      Bladder Cancer (Amsterdam, Netherlands)
      IOS Press
      Bladder cancer, micropapillary

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          Abstract

          Introduction: Micropapillary bladder cancer (MPBC) is a variant histology of urothelial carcinoma (UC) that is associated with poor outcomes however given its rarity, little is known outside of institutional reports. We sought to use a population-level cancer database to assess survival outcomes in patients treated with surgery, radiation therapy and/or chemotherapy.

          Materials and Methods: The National Cancer Database (NCDB) was queried for all cases of MPBC and UC using International Classification of Disease-O-3 morphologic codes between 2004–2014. Primary outcome was survival outcomes stratified by treatment modality. Treatments included radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC).

          Results: Overall 869 patients with MPBC and 389,603 patients with UC met the inclusion criteria. Median age of the MPBC cohort was 69.9 years (58.9–80.9) with the majority of the cohort presenting with high-grade (89.3%) and muscle invasive or locally advanced disease (47.6%). For cT1 MPBC, outcomes of RC and BPS were not statistically different. For≥cT2 disease, NAC showed a survival benefit compared with RC alone for UC but not for MPBC. On multivariable analysis, MPBC histology independently predicted worse increased risk of death. On subanalysis of the MPBC RC patients, NAC did not improve survival outcomes compared with RC alone.

          Conclusions: Neoadjuvant chemotherapy utilization and early cystectomy did not show a survival benefit in patients with MPBC. This histology independently predicts decreased survival and prognosis is poor regardless of treatment modality. Further research should focus on developing better treatment options for this rare disease.

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          Most cited references17

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          Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer

          Background Progression of conventional urothelial carcinoma of the bladder to a tumor with unique microscopic features referred to as micropapillary carcinoma is coupled with aggressive clinical behavior signified by a high propensity for metastasis to regional lymph nodes and distant organs resulting in shorter survival. Objective To analyze the expression profile of micropapillary cancer and define its molecular features relevant to clinical behavior. Design, setting, and participants We retrospectively identified 43 patients with micropapillary bladder cancers and a reference set of 89 patients with conventional urothelial carcinomas and performed whole-genome expression mRNA profiling. Outcome, measurements and statistical analysis The tumors were segregated into distinct groups according to hierarchical clustering analyses. In addition, the tumors were classified according to luminal, p53-like, and basal categories using previously described algorithm. We applied IPA and GSEA for pathway analyses. Cox proportional hazards models and Kaplan-Meier methods were used to assess the relationship between survival and molecular subtypes. The expression profile of micropapillary cancer was validated for selected markers by immunohistochemistry on parallel tissue microarrays. Results We show that the striking features of micropapillary cancer are downregulation of miR-296 and activation of chromatin-remodeling complex RUVBL1. In contrast to conventional urothelial carcinomas which, based on their expression, can be equally divided into luminal and basal subtypes, micropapillary cancer is almost exclusively luminal, displaying enrichment of active PPARγ and suppression of p63 target genes. As with conventional luminal urothelial carcinomas, a subset of micropapillary cancers exhibit activation of wild-type p53 downstream genes and represent the most aggressive molecular subtype of the disease, with the shortest survival. Conclusions Micropapillary cancer evolves through the luminal pathway and is characterized by the activation of miR-296 and RUVBL1 target genes. Limitations The involvement of miR-296 and RUVBL1 in the development of micropapillary bladder cancer was identified by the analyses of correlative associations of genome expression profiles and requires mechanistic validation. Patient summary Our observations have important implications for prognosis and for possible future development of more effective therapies for micropapillary bladder cancer.
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            Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients.

            Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience. The authors reviewed the records of 100 consecutive patients with micropapillary bladder cancer who were evaluated at The University of Texas M. D. Anderson Cancer Center. The mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7 patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan-Meier estimates of 5-year and 10-year overall survival (OS) rates were 51% and 24%, respectively. Bladder-sparing therapy with intravesical bacillus Calmette-Guerin therapy was attempted in 27 of 44 patients with nonmuscle-invasive disease; 67% (18 patients) developed disease progression (>or=cT2), including 22% who developed metastatic disease. Of 55 patients undergoing radical cystectomy for surgically resectable disease (
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              Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: impact of mandatory central pathology review at a large referral hospital.

              Urothelial carcinoma (UC) demonstrating variant histologic differentiation is associated with poor outcomes, and certain variants exhibit differing therapeutic responses compared with pure conventional UC. Little is known about the awareness and reporting practices of UC with variant histology in community practice.
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                Author and article information

                Journal
                Bladder Cancer
                Bladder Cancer
                BLC
                Bladder Cancer (Amsterdam, Netherlands)
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                2352-3727
                2352-3735
                24 October 2016
                27 October 2016
                2016
                : 2
                : 4
                : 415-423
                Affiliations
                [a ] Department of Urology, Columbia University Medical Center , New York, NY, USA
                [b ] Department of Biostatistics, Mailman School of Public Health, Columbia University , New York, NY, USA
                Author notes
                [* ]Correspondence to: Sven Wenske, Department of Urology, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington, 11th Floor, New York, NY 10032, USA. Tel.: +1 212 305 5526; Fax: +1 212 305 6813; E-mail: sw2510@ 123456cumc.columbia.edu .
                Article
                BLC160066
                10.3233/BLC-160066
                5181670
                28035322
                96683fa1-cf6c-4be0-bb12-f99b53a778df
                IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Research Report

                bladder cancer,micropapillary
                bladder cancer, micropapillary

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