Contemporary treatment patterns and outcomes of sarcomatoid bladder cancer: Beyond the Abstract

In 2016, 750,000 bladder cancer survivors are estimated to live in the United States alone and over 75,000 new cases will be diagnosed.1,2 The vast majority are urothelial tumors however a small proportion of these will be variant histologies. Sarcomatoid carcinoma (SaC) is such a subtype and is estimated to represent 0.3% of all urothelial cancers.3 Much of our knowledge about this disease is derived from case studies or single-institution reports of which have totaled fewer than 100 cases in the last several decades.4-7

Variant histologies in general are associated with a poor prognosis and sarcomatoid bladder cancer is thought to be an aggressive, chemotherapy resistant malignancy. However due to its rarity, it is difficult to identify treatment strategies without pooling data from many institutions.  Thus we set out to characterize this cancer subtype using the National Cancer Database (NCDB), a large population-level database that captures data from over 1,500 hospitals in North America. 

We identified 1,230 patients with a primary sarcomatoid bladder cancer however after excluding patients with metastatic disease (locoregional or distant) only 489 of these patients had complete demographic, clinical and outcomes information available for analysis. It is noteworthy that a large proportion of patients were excluded due to having an “other cancer diagnosis.” We did this in order to ensure a pure cohort and to more reliably capture patients who underwent chemotherapy or radiotherapy for the indication of sarcomatoid bladder cancer. 

Among localized SaC, patients who underwent bladder preservation surgery (with or without additional chemotherapy/radiotherapy) had worse survival outcomes compared to patients who underwent radical cystectomy (RC). However when analyzing the RC cohorts, we found no significant differences in median survival between the radical cystectomy (RC) alone, neoadjuvant chemotherapy (NAC) + RC and RC + adjuvant chemotherapy (AC) cohorts. In addition, neither NAC + RC nor AC + RC were independent predictors of survival on cox proportional hazards analysis. 

This study is limited by several important factors. An inherent limitation of studies relying on national, institutional level data is the lack of specific treatment parameters, for instance the radiation dose or lymph node dissection template, that are likely to be related to disease outcomes. As a retrospective analysis, there is the risk of confounding by indication that cannot be fully eliminated through multivariable analysis. It is likely that patients who received only bladder preservation surgery were sicker or otherwise unfit for radical cystectomy thus resulting in selection bias for our survival outcomes. Similarly patients who underwent RC alone may have been unable to tolerate NAC or AC. 

Our findings largely support the previous literature calling for an aggressive approach to clinically localized SaC management. With our median survival estimate of 18.4 months across all patients with SaC and over 50% presenting with muscle-invasive disease, this variant histology clearly has a poor prognosis and demands further investigation. As pathologists increasingly recognize SaC in TUR specimens the numbers will grow and allow for more robust analysis in the future. 

Written by: Wilson Sui, Justin T. Matulay, G. Joel DeCastro

References:
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66(1): 7-30.

2. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016; 66(4): 271-89.

3. Bansal A, Kumar N, Sharma SC. Sarcomatoid variant of urothelial carcinoma of the urinary bladder. J Cancer Res Ther 2013; 9(4): 571-3.

4. Young RH, Wick Mr Fau - Mills SE, Mills SE. Sarcomatoid carcinoma of the urinary bladder. A clinicopathologic analysis of 12 cases and review of the literature. (0002-9173 (Print)).

5. Fatima N, Canter DJ, Carthon BC, et al. Sarcomatoid urothelial carcinoma of the bladder: a contemporary clinicopathologic analysis of 37 cases. Can J Urol 2015; 22(3): 7783-7.

6. Eble JN, Young RH. Carcinoma of the urinary bladder: a review of its diverse morphology. Semin Diagn Pathol 1997; 14(2): 98-108.

7. Reuter VE. Sarcomatoid lesions of the urogenital tract. Semin Diagn Pathol 1993; 10(2): 188-201.

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