A multi-institutional comparison of clinicopathologic characteristics and oncologic outcomes of upper tract urothelial carcinoma in China and the United States: Beyond the Abstract

Upper tract urothelial carcinoma (UTUC) is relatively uncommon, comprising 5-10% of all urothelial carcinomas.  There have been a number of risk factors identified for UTUC including exposure to tobacco, aromatic amines, phenacetin, aristolochic acid, or arsenic, prior bladder cancer, chronic upper tract inflammation, and genetic associations such as Lynch syndrome. 

Interestingly, certain epidemiologic differences become evident when comparing UTUC series emerging from the U.S. or Western European countries versus Asian regions such as Taiwan or mainland China.  Some of these differences include gender distribution, age, and tumor location of UTUC.  These apparent differences have not yet been highlighted extensively in the contemporary literature, however, and warrant further attention.

Indeed, the reasons for such observations remain poorly understood.  It is conceivable that geographic differences in risk factors for UTUC may be partially accountable.  For example, aristolochic acid is primarily endemic to China and the Balkan regions, while its use is less prevalent in Western countries.  In the latter, tobacco use may be the more likely culprit for UTUC pathogenesis.  Alternatively, it is certainly possible that there are accountable genetic variations between these ethnic groups or that the underlying biology of UTUC itself differs.  To help shed some light on these questions, for the first time to our knowledge, we directly compared clinicopathologic characteristics and oncologic outcomes between UTUC patients treated in China and the U.S. using a large multi-institutional international database (n=775).

We found several interesting differences between the two cohorts, many of which are consistent with findings from prior series.  In particular, patients in the U.S. were slightly older and had worse baseline comorbid status and overall survival compared to UTUC patients in China.  Despite this, patients in China exhibited relatively worse prognostic features including hydronephrosis, high grade disease, and muscle invasion.  Significant predictors for oncologic endpoints on multivariable analysis were discordant between the two countries.

Undoubtedly, our results must be contextualized within its limitations, including its retrospective nature, heterogeneity in clinical management patterns, and missing variables such as aristolochic acid use.  Nonetheless, the striking differences observed in our study cannot be ignored, and future studies should aim to understand why this may be the case.  While evaluation and management patterns likely differ between the two countries—perhaps an opportunity for public health intervention—our findings may reflect exciting fundamental differences in the underlying pathophysiology of disease.  These observed differences are important to note in clinical trial design with respect to, for example, patient composition, anticipated outcomes, and power calculations.  Future case-matched studies should further incorporate exposure to environmental risk factors and underlying genetic factors to clarify this interesting phenomenon and potentially carve the path to targeted approaches to therapy.

Written by: Nirmish Singla, M.D., Vitaly Margulis, M.D.Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX

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