Obese individuals are at increased risk for renal cell carcinoma (RCC) compared with those of normal weight, a recent study suggests.
In addition, results showed that weight loss around the time diagnosis, and not low body mass index (BMI) by itself, is associated with worse survival. The finding challenges what has been called the “obesity paradox,” the observation that obesity increases the likelihood of RCC but decreases the risk of RCC-related death, according to investigators.
In a meta-analysis of data from 3 prospective studies, a cumulative average BMI of 30 kg/m2 or higher was significantly associated with an approximately 2.2-fold increased risk for total RCC and 2.0-fold increased risk for fatal RCC compared with a BMI of 18 to less than 25 kg/m2, Rebecca E. Graff, ScD, of the University of California, San Francisco, and colleagues reported in European Urology.
BMI prior to diagnosis was not associated with RCC-related death, but the first post-diagnosis BMI of 30 kg/m2 or higher was significantly associated with a 49% decreased risk of RCC-related death compared with a BMI of 18 to less than 25 kg/m2. In addition, a weight change from pre- to post-diagnosis was significantly and inversely associated with RCC-related mortality. For example, a weight gain of 10 or more pounds from pre- to post-diagnosis was significantly associated with a 48% decreased risk for RCC-related death compared with stable weight. Kaplan-Meier and multivariable analyses demonstrated that patients who transitioned from being overweight or obese before diagnosis to normal weight after diagnosis had the worst survival outcomes, Dr Graff’s team reported.
“These results support obesity as a risk factor for total and fatal RCC,” the authors concluded. “They undermine the obesity paradox by suggesting that weight loss around diagnosis, and not low BMI by itself, is associated with worse prognosis.”
The latest analysis examined data from the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS) 1 and 2. The investigators presented RCC incidence analyses for 48,112, 113,932, and 110,623 participants in the HPFS, NHS1, and NHS2 studies, respectively. RCC developed in 293 HPFS participants, 401 NHS1 participants, and 111 NHS2 participants.
The median follow-up among individuals diagnosed with RCC who did not die from it was 9.9 years in HPFS and 10 years in NHS.
“Reverse causation is potentially important in obesity and cancer studies, as undiagnosed aggressive disease may cause weight loss before diagnosis, such that diagnostic BMI may not accurately reflect adult weight,” Dr Graff and colleagues wrote. Their results support a role for reverse causation in the obesity paradox whereby post-diagnosis BMI, but not pre-diagnosis BMI, was associated with RCC-related mortality as was pre-diagnosis to post-diagnosis weight loss, according to the investigators.
Despite their findings, the investigators acknowledged that it remains possible obesity confers a survival benefit in patients with RCC. “Kidney tumors in obese individuals could be less biologically aggressive, or the increased metabolic reserve of obesity could prolong survival.”
Graff RE, Wilson KM, Sanchez A, et al. Obesity in relation to renal cell carcinoma incidence and survival in three prospective studies. Eur Urol. Published online June 14, 2022. doi:10.1016/j.eururo.2022.04.032