Body Mass Index and Survival in a Prospective Randomized Trial of Localized High Risk Renal Cell Carcinoma - Beyond the Abstract

In this manuscript, we evaluated the relationship between body mass index (BMI) and disease-free and overall survival in a large, international prospective randomized clinical trial of patients with fully resected, high risk clear cell renal cell carcinoma (RCC). The majority of work investigating this relationship has utilized retrospectively collected data outside the realm of controlled clinical trials. Because data from clinical trials is carefully controlled and collected, we felt that the utilization of this high-quality data to address this clinical question would be a meaningful addition to the body of knowledge in this area.  

Additionally, there is a significant body of evidence suggesting a possible obesity paradox in RCC. Virtually all epidemiologic studies suggest that increased adiposity increases ones risk for the development of RCC, and yet several studies have suggested that increased adiposity may predispose to better survival from RCC. In short, increased adiposity predisposes to RCC, however should you develop RCC, your prognoses may be better than leaner counterparts. Our findings were consistent with this: we found that obese patients had a lower probability of lymph node involvement (when controlling for both patient and tumor-related factors). In addition, we found that obese and morbidly obese patients had better overall survival, and a trend towards better disease-free survival, also when controlling for both patient and tumor-related factors.  

One hypothesis explaining these findings is that increased adiposity induces clear-cell RCC development, but those tumors which develop in the obese environment tend towards a more indolent course. Whether or not this indolence is reflected in traditional factors such as grade and stage is debatable.  In our study, when controlling for grade and stage, we still found a survival benefit in the obese, suggesting that either stage and grade do not fully capture the biological potential of these tumors, or that the host response to these tumors has an influence on their ultimate clinical behavior... or both. Our study, however, was limited to patients with high-risk tumors, and as such was not optimally designed to evaluate this specific question.  Others, however, have not found an improved survival in the obese after controlling for stage and grade. Still, this leaves open the possibility that obese patients demonstrate improved survival because they form smaller tumors with less aggressive nuclear features. Regardless, whether obese patients do better because they form smaller, less aggressive tumors, or because the obese environment in the host is less hospitable to these tumors, or both, still means that on the whole these patients have a better prognosis. 

The findings of this study are clinically applicable. Renal surgery in the obese is more difficult and more time-consuming.  In those with significant co-morbidity, it may be appropriate to consider deferring treatment in lieu of actives surveillance, if the tumors appear small and if their grade is low. While our study did not evaluate the natural history of observed lesions on active surveillance in the obese, it does support the concept that some of these lesions may display indolent biology, and that in the obese and morbidly obese, surveillance may be appropriate.   

Written By: Nicholas M Donin,  Urology, David Geffen School of Medicine at UCLA.  

Read the Abstract:

Donin NM, Pantuck A, Klöpfer P, Bevan P, Fall B4, Said J, Belldegrun AS, Chamie K. Body Mass Index and Survival in a Prospective Randomized Trial of Localized High Risk Renal Cell Carcinoma. Cancer Epidemiol Biomarkers Prev cebp.0226.2016; Published OnlineFirst July 14, 2016;  doi: 10.1158/1055-9965.EPI-16-0226