Overweight, obesity linked to better survival in kidney cancer

Kidney cancer patients with body mass index (BMI) above the normal range appear to have more favourable outcomes than those who are underweight, results of a recent systematic review and meta-analysis have shown.

“While there was a significant association between higher BMI and more favourable kidney cancer outcomes, due to significant heterogeneity of studies, multicentre large-scale high quality prospective studies as well as further research on fundamental biological mechanisms are required to elucidate this controversial finding,” the researchers said.

The databases of Medline, Embase, ProQuest, PubMed, and Google Scholar were searched between its inception and December 2018 for literature published in English. The researchers used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting.

Thirty-four publications, comprising 50,717 patients overall, met the eligibility criteria. Most of these studies assessed the association between BMI and cancer-specific survival. Overweight and obese patients were more likely to have better cancer-specific survival than those with normal BMI (hazard ratio [HR], 0.85, 95 percent confidence interval [CI], 0.79–0.93). [J Urol 2021;205:346-355]

This trend persisted for progression-free (HR, 0.68, 95 percent CI, 0.59–0.78) and overall survival (HR, 0.66, 95 percent CI, 0.55–0.79). On the other hand, those who were underweight demonstrated worse cancer-specific survival (HR, 2.16, 95 percent CI, 1.15–4.04).

Certain drawbacks limited the interpretation of these findings, including the retrospective design in majority of the studies, heterogeneity in study population, BMI classification, and covariates in multivariate analysis.

Interestingly, the concept of obesity paradox was also found in patients with various cancers, such as colorectal, lymphoma, leukaemia, thyroid, metastatic lung, and breast cancers. [JAMA Oncol 2016;2: 1137-1145]

Constantinos and colleagues suggested that higher BMI preserved more fat and muscle mass, which reflected better nutritional status and thus conferred potential survival advantage. This hypothesis was consistent with other measures of adiposity such as waist/hip ratio. [J Card Fail 2003;9:29-35; Prog Cardiovasc Dis 2018;61:151-156]

“This phenomenon was also shown in other chronic medical conditions such as chronic obstructive pulmonary disease and chronic renal failure,” the researchers said. [Int J Chron Obstruct Pulmon Dis 2014;9:1337-1346; Kidney Int Rep 2017;2:271-281]

In addition, several theories have been considered to explain the apparent benefit of overweight and obesity in cancer outcomes.

For instance, “[o]verweight and obese patients may undergo more opportunistic testing for other medical reasons and hence are more likely to be diagnosed with incidental small renal mass at an earlier stage,” the researchers said.

Several studies found that obese patients tended to have more favourable tumour biology, with downregulated expression of metabolic and fatty acid genes that are crucial for tumour proliferation. [J Urol 2010;183:e448; Urology 2006;68:741-746; J Natl Cancer Inst 2013;105:1862-1870]

In addition, “excessive perirenal fat can act as a barrier to cancer progression but has been recently refuted. Sufficient nutritional status may also protect against treatment related stress or facilitate enhanced response to treatment,” the researchers said.