HIGH BMI INCREASES SURVIVAL IN RENAL CANCER

Orlando, FLORIDA — It is seemingly a paradox. Obesity and overweight are established risk factors for developing renal cell carcinoma (RCC) as well as for a number other cancer types. But a new validation data analysis has confirmed that excess weight in patients with RCC may be beneficial.

In a cohort of over 4000 patients, researchers found that those with a higher body mass index (BMI) were more likely to have a higher overall survival, longer time to treatment failure, and better tumor shrinkage when compared with patients with normal or lower BMI.

Within the cohort, 1829 (39%) patients were of normal weight or underweight (BMI < 25 kg/m²) and were described in the study as having lower BMI, and 2828 (61%) were overweight or obese (BMI ≥ 25 kg/m²) and were described as having a high BMI.

Overall, a high BMI was associated with significantly longer overall survival compared with those with a lower BMI (23.4 months vs 14.5 months; hazard ratio (HR), 0.830; P =.0008). This translated into a 17% decreased risk for mortality in the high-BMI group when the analysis was adjusted.

In addition, the high-BMI group had a significant 18% decreased risk for disease progression.

Some previous reports have suggested that RCC developing in an obesogenic environment may be more indolent, explained lead author Laurence Albiges, MD, PhD, a medical oncologist at the Institut Gustave Roussy, Paris, France, who presented the findings here at the 2015 Genitourinary Symposium.

An analysis from the Cancer Genome Atlas (TCGA) showed that lower-stage disease was associated with a high BMI, but there were no specific genomic features detected in obese patients. It also revealed that fatty acid synthase (FASN) gene expression was different between low- and high-BMI patients.

In addition, Dr Albiges noted that in the metastatic setting and in patients treated with targeted therapies, her group recently also reported on the favorable impact of BMI on survival in the International mRCC Database Consortium (IMDC).

External Validation

"The current work aims to externally validate this finding and characterize the underlying biology," said Dr Albiges, who is currently a visiting scientist at Dana-Farber's Lank Center for Genitourinary Cancer in Boston, Massachusetts.

The authors conducted an analysis of 4657 metastatic RCC patients who were treated on phase 2-3 clinical trials sponsored by Pfizer from 2003 to 2013. In this cohort, they assessed the impact of BMI on overall survival, progression-free survival (PFS), and overall response rate.

They also analyzed patients with metastatic disease from the clear cell RCC cohort of TCGA dataset to correlate the expression of FASN with BMI and overall survival.

The data was adjusted for a number of confounders including age, gender, ethnicity, prior nephrectomy, tumor histology, IMDC risk groups, and liver and bone metastases.

In addition to improved overall survival, Dr Albiges and her team found that high-BMI patients had better PFS (8.2 months vs 5.5 months; HR, 0.821;  P < .0001) and overall response rate (25.3% vs 17.6%; odds ratio, 1.527; P < .001).

These results remained valid when stratified by line of therapy, but when stratified by histological subtype, the favorable outcome associated with high BMI was only observed in clear cell RCC.

Role of FASN Unclear

In the second part of their analysis, the authors found that FASN gene expression was associated with overall survival in only one of the two cohorts analyzed.

Among the TCGA dataset (n = 61), there was a trend toward improved overall survival in the high-BMI group (P = .07).

FASN gene expression was inversely correlated with both overall survival (P = .002) and BMI (P = .034).

"There was lower FASN expression in high BMI," said Dr Albiges, "And high FASN was associated with lower overall survival."

In the TCGA dataset, FASN gene expression is associated with overall survival and suggests further exploration of the role of fatty acid metabolism in RCC, she said.

But in the IMDC biospecimen cohort (n = 146) that was stained for FASN, it was not found to be an independent prognosis factor for overall survival. BMI was associated with overall survival independently of FASN, even though obese patients were less likely to express FASN.

"Given that this finding was observed in clear cell RCC only, we hypothesize that lipid metabolism may be modulated by the fat laden tumors cells," concluded Dr Albiges. "FASN staining in the IMDC cohort is ongoing to better investigate the obesity paradox in metastatic disease."

Increased BMI correlates with a superior outcome in kidney cancer, although the reasons and pathophysiology are not quite spelled out yet, commented paper discussant Ulka N. Vaishampayan, MD, from the Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.

"The FASN story is being looked at and continues on," she said.

Attempts to predict prognosis and response to specific therapies based on factors that include BMI changes are steps in the right direction, Dr Vaishampayan continued. "The interaction of low BMI and poor risk factors should be explored."

Additionally, the impact of medications such as steroids on BMI needs to be considered, she added. "Comparative effectiveness of each of these factors should be contemplated especially when interventions are considered."

Dr Albiges reports relationships with Amgen, Novartis, Pfizer, and Sanofi. Several coauthors also report relationships with industry, as noted in the abstract. 

Genitourinary Cancers Symposium (GUCS) 2015. Abstract 405. Presented February 27, 2015.