An Epidemiologic and Genomic Investigation Into the Obesity Paradox in Renal Cell Carcinoma

Hakimi, A. Ari; Furberg, Helena; Zabor, Emily C.; Jacobsen, Anders; Schultz, Nikolaus; Ciriello, Giovanni; Mikklineni, Nina; Fiegoli, Brandon; Kim, Philip H.; Voss, Martin H.; Shen, Hui; Laird, Peter W.; Sander, Chris; Reuter, Victor E.; Motzer, Robert J.; Hsieh, James J.; Russo, Paul

doi:10.1093/jnci/djt310

Cited by 253 publications

(213 citation statements)

References 34 publications

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“…In the present study, morbidly obese patients with RCC treated with surgery were younger, had lower grade tumours, and were less likely to have metastatic RCC at presentation, similar to other studies [6,21]. Multivariate analysis was used to independently evaluate predictors of cancer outcomes and the present study did not identify obesity as a predictor of recurrence or cancer mortality, despite considering multiple BMI definitions of obesity and other known predictive variables.…”

Section: Discussionsupporting

confidence: 76%

“…Given that the incidence of both RCC [18] and extreme obesity [9] are increasing, urologists will increasingly have to consider the potential benefits of treatment vs the higher risk of surgical and anaesthetic complications in very obese patients [19]. Recent studies have suggested that obesity increases the risk of developing RCC [1], although mild or moderate obesity is not necessarily associated with worse outcomes [4][5][6][7][19][20][21][22]. In the present study, we evaluated the largest series to date of RCC patients with extreme obesity, and found similar CSS and recurrence rates when compared with patients with lower body mass.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of studies that evaluate RCC in obese patients have defined obesity as having a BMI ≥ 30 kg/m 2 [5,6,21], but this definition may not accurately reflect some patient's overall health or expected longevity [23] In 2013, a metaanalysis of 2.9 million patients evaluated the association of all-cause mortality with BMI. Interestingly, the authors found no differences in mortality in patients of ideal body weight (BMI 20-24.9 kg/m 2 ) compared with those described as overweight (BMI 25-29.9 kg/m 2 ), or in patients with class 1 obesity (BMI 30-34.9 kg/m 2 ), while mortality rates were higher only in patients with BMI ≥ 35 kg/m 2 [24].…”

Section: Discussionmentioning

confidence: 99%

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Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer

et al. 2015

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ObjectiveTo assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m 2 ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrencefree survival (RFS) after surgical treatment for renal cell carcinoma (RCC). Patients and MethodsAfter institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. ResultsIn all, 100 patients (11.9%) with a BMI ≥ 40 kg/m 2 and 743 patients (88.1%) with a BMI < 40 kg/m 2 who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m 2 was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m 2 was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m 2 was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/ m 2 and BMI ≥ 40 kg/m 2 , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m 2 and BMI ≥ 40 kg/m 2 , respectively. The 5-year RFS rates for BMI < 40 kg/m 2 and BMI ≥ 40 kg/m 2 were 84.1 and 90.6%, respectively (P = 0.48). ConclusionsExtreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer

et al. 2015

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“…1,2 Paradoxically, higher BMI appears to be associated with better prognosis among RCC patients. 3,4 As BMI is an indirect measure of adiposity that does not distinguish between adipose tissue and lean mass, 5 other metrics of body size should be considered in relation to RCC prognosis.…”

Section: Introductionmentioning

confidence: 99%

Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

Hakimi

Zabor

Bury

et al. 2014

CUAJ

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Introduction: Visceral adiposity has been inconsistently associated with clinicopathologic features and outcomes of clear cell renal cell carcinoma (ccRCC); however, most studies were conducted in non-Western populations. We evaluated the associations between visceral and subcutaneous adiposity and clinicopathological characteristics of non-metastatic ccRCC patients in a Western population. Methods: The medical records of 220 surgically treated ccRCC patients with documented preoperative body mass index (BMI) and computed tomography (CT) scans were retrospectively reviewed. Nineteen patients with stage IV disease were excluded. Visceral (VFA) and subcutaneous fat area (SFA) were computed from preoperative CT scans. Correlations between obesity measures were assessed with Pearson correlation. Associations between obesity measures and pathologic features were evaluated using logistic regression models adjusted for sex. Overall survival (OS) probabilities were estimated using Cox regression analysis. The log-rank test was used for group comparisons. Results: The study cohort comprised 150 men and 51 women. Women had higher SFA (p = 0.01) but lower VFA (p < 0.001) than men. BMI was highly correlated with SFA (r = 0.804) and moderately correlated with VFA (r = 0.542). SFA and VFA were weakly correlated (r = 0.367). An increased BMI was associated with a better OS (p = 0.028). When adjusting for sex, neither SFA nor VFA was significantly associated with tumour grade, stage, or OS. Conclusions: Consistent with prior reports, our study suggests that increased BMI is associated with a better OS for patient with nonmetastatic ccRCC. Despite the high correlation between SFA and BMI, neither SFA nor VFA were significantly associated with tumour stage, grade, or OS in the current study; however, further studies in larger cohorts are required to validate this finding.

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“…Furberg, Hakimi and their colleagues pulled up the medical data from these 126 people and calculated each patient's BMI just before surgery 4 . They wanted to see if a person's BMI had any bearing on the tumours' gene expression.…”

Section: Finding the Mechanismmentioning

confidence: 99%

Obesity: The fat advantage

Gupta

2016

Nature

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An Epidemiologic and Genomic Investigation Into the Obesity Paradox in Renal Cell Carcinoma

Abstract: Our findings suggest that although BMI is not an independent prognostic factor for CSM after controlling for stage and grade, tumors developing in an obesogenic environment may be more indolent.

Cited by 253 publications

References 34 publications

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer

Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

Obesity: The fat advantage

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