Clinical Risk Stratification in Patients with Surgically Resectable Micropapillary Bladder Cancer: Beyond the Abstract

Micropapillary bladder cancer (MPBC) is considered an especially aggressive variant of bladder cancer. This article reports on the clinical outcomes in patients with surgically resectable MPBC undergoing radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) with a focus on risk group stratification1.

Our prior publications have been instrumental in raising awareness of this variant of bladder cancer and helped drive appropriate therapy for patients (e.g. early cystectomy for non-muscle invasive bladder cancer patients, expedient radical cystectomy for patients with muscle invasive bladder cancer)2. In the present study, which is the largest series to date, we expanded on our prior efforts in order to refine risk group selection. Our findings show three distinct risk subgroups of surgically resectable MPBC with distinct survival outcomes at 5-years as follows: low-risk: 92%; high-risk: 51% and highest-risk: 17%, respectively (p<0.001; Figure 1). 

This is also the largest series assessing the role of neoadjuvant chemotherapy in patients with MPBC; overall 5-year DSS rate was 54% for patients who received chemotherapy and 60% for patients treated with up-front cystectomy (p=0.54). When survival differences were examined within risk groups, patients with high-risk disease appeared to derive benefit from neoadjuvant chemotherapy (5-year DSS rate, 79% vs. 43%). Our finding that chemotherapy did not have an impact on DSS in the low-risk group reinforces our previous finding that upfront early cystectomy offers the best survival in this group3. Unfortunately, patients in the highest-risk category (those with tumor-associated hydronephrosis) had poor outcomes regardless of mode of therapy. 

Pathologic downstaging, which is considered a surrogate marker for survival in BC, was also associated with improved OS and DSS. In fact, patients with MPBC downstaged to <pT1pN0 at RC did well regardless of whether downstaging was achieved with NAC or TUR alone. However, it is interesting that among patients whose disease was not downstaged, those undergoing upfront RC had better outcomes than those treated with NAC (5-year DSS rate, 52% vs. 17%), a difference that cannot be explained by adjuvant chemotherapy because implementation was equal. This finding gives emphasis to the need for identification of markers for chemosensitivity (e.g. molecular profiling) to avoid delay of RC in patients with MPBC who will not respond to chemotherapy. The significant activation of miR-296 target genes in MPBC identified by our group in a recent study represents an attractive target.4

Presence of histologic subtypes in BC have implications for prognosis and management. Our series significantly adds to the few reports on the role of NAC for MPBC. However, further studies in a prospective manner or validation with external multicenter data sets in order to overcome biases inherent to single-center reports are encouraged before treatment recommendations can be made.

Written by: Mario I. Fernández, Ashish M. Kamat*
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX
*Correspondence: Ashish M. Kamat, Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1155 Pressler, Houston, TX 77030  

1. Fernandez, M. I., Williams, S. B., Willis, D. L. et al.: Clinical Risk Stratification in Patients with Surgically Resectable Micropapillary Bladder Cancer. BJU Int, 2016

2. Kamat, A. M., Dinney, C. P., Gee, J. R. et al.: Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients. Cancer, 110: 62, 2007

3. Willis, D. L., Fernandez, M. I., Dickstein, R. J. et al.: Clinical Outcomes of cT1 Micropapillary Bladder Cancer. J Urol, 2014

4. Guo, C. C., Dadhania, V., Zhang, L. et al.: Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer. Eur Urol, 2016

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