Renal cell carcinoma survival and body mass index: a dose-response meta-analysis reveals another potential paradox within a paradox

BACKGROUND: In healthy subjects increasing body mass index (BMI) leads to greater mortality from a range of causes. Following onset of specific diseases, however, the reverse is often found: called the 'obesity paradox'. But we recently observed the phenomenon called the 'paradox within the paradox' for stroke patients.

OBJECTIVE: The objective of our study was to examine the effect of each unit increase in BMI on renal cancer-specific survival (CSS), cancer-specific mortality, overall survival (OS) and overall mortality.

DESIGN: Random-effects generalized least squares models for trend estimation were used to analyze the data. Eight studies, comprising of 8699 survivals of 10 512 renal cell carcinoma (RCC) patients met the inclusion criteria, including 5 on CSS and 3 on OS.

RESULTS: The association of BMI with CSS and OS was non-linear (P<0.0001, P=0.004, respectively). We observed that CSS increased in relation to BMI, indicating that there was the obesity paradox in RCC. However, each unit increase in BMI over 25 was associated with decreased OS, indicating that RCC may also exhibit a paradox within the paradox.

CONCLUSIONS: Inconsistent effects of increases in BMI on CSS and OS, as previously observed for stroke, creates a paradox (different directions of mortality for different causes) within the obesity paradox.