Proof of “obesity paradox” in kidney cancer continues to grow

A large systemic review of renal cell carcinoma (RCC) trials has provided additional evidence of the “obesity paradox,” the phenomenon of patients with elevated body mass index (BMI) having a more favorable kidney cancer prognosis, including a survival advantage.¹

The review of data from 50,717 patients showed that cancer specific survival was improved in overweight and obese patients with RCC compared with patients with normal BMI (HR, 0.85). Similar patterns were observed with progression-free survival (HR, 0.68) and overall survival (HR, 0.66). Conversely, underweight patients had inferior cancer specific survival outcomes compared with overweight/obese patients (HR, 2.16).

The results of this analysis corroborate several prior studies demonstrating a link between higher BMI and improved prognosis in patients with RCC.

“This is the largest systematic review evaluating the potential phenomenon of the obesity paradox in kidney cancer outcomes. It demonstrated a favorable effect of body mass index on kidney cancer outcomes,” the researchers wrote.

The data for the trial were pooled from 34 publications compiled from a computerized search of the Medline, Embase, ProQuest, PubMed, and Google Scholar databases.

The investigators wrote that the specific mechanism of how obesity might improve outcomes in patients with RCC remains unknown; however, they shared several theoretical explanations:

• Patients with a higher BMI are more likely to receive medical testing for other reasons and may be more likely to have an incidental renal mass diagnosed at an earlier stage.
• Some research has demonstrated a more favorable tumor biology in obese patients, specifically shown by downregulated expression of metabolic and fatty acid genes that are a key component of tumor growth.
• The role of adipose tissue at the molecular level is also considered a factor.

The researchers listed several limitations to their analysis, including, “the retrospective design in the majority of studies, selection bias, collider stratification bias, heterogeneity between series in terms of the study population, BMI classification, inconsistent inclusion of covariates in multivariate analysis, and a lack of long-term follow-up including BMI trajectory throughout the study period. Prospective studies are also not devoid of any potential misclassification bias due to change in BMI throughout follow-up period.”

Accordingly, the researchers recommend additional research into the fundamental biological mechanisms of the BMI paradox in order to determine the true significance of BMI on outcomes in patients with RCC.

Summarizing the findings in an accompanying editorial, Alp Tuna Beksac, MD, wrote, “Given the excellent oncologic outcomes in organ confined RCC, an analysis of an advanced RCC cohort would have been a valuable addition to the study. This was not possible since the majority of the studies either exclusively or predominantly consisted of patients with localized RCC. However, there is evidence in the literature that supports the authors’ findings in the advanced RCC cohort (reference 5 in article). While this study might not have an immediate impact on current day practice, hopefully, it will encourage researchers to focus on understanding the biological mechanisms of this paradox to further understand RCC, and help individualize RCC treatment in the future.”²

Reference

1. Kim LH, Doan P, He Y, et al. A systematic review and meta-analysis of the significance of body mass index on kidney cancer outcomes. J Urol. 2021;205(2):346-355. doi: 10.1097/JU.0000000000001377

2. Beksac AT. Editorial comment. J Urol. 2021;205(2):355. Doi: 10.1097/JU.0000000000001377.01