Impact of Hemoglobin A1c on the Obesity Paradox and Survival in Patients With Non-Metastatic Renal Cell Carcinoma.

INTRODUCTION

The "obesity paradox" suggests that patients with various cancers, including renal cell carcinoma (RCC), and body mass index (BMI) ≥ 30 kg/m2 may experience improved survival. However, the influence of glycemic control on this association remains unclear. This study evaluates whether elevated hemoglobin A1c (HbA1c) modifies the survival benefit associated with the obesity paradox in patients undergoing nephrectomy for non-metastatic RCC.

METHODS

Patients undergoing nephrectomy for non-metastatic RCC at a single academic center from 2005 to 2024 were screened for inclusion. Inclusion criteria included HbA1c measured within 3 months preoperatively and ≥ 6 months of follow-up. Obesity was defined as BMI ≥ 30 kg/m²; elevated HbA1c as ≥ 7%. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Cox proportional hazards models and Kaplan-Meier analysis.

RESULTS

770 patients met inclusion criteria. Median follow-up was 45.2 months; 172 (22%) mortality events occurred. Among patients with HbA1c < 7%, patients with obesity demonstrated improved CSS (HR 0.21 [95% CI, 0.09-0.48], P < .001) compared to non-obese counterparts after controlling for confounders. In patients with HbA1c ≥ 7%, no significant survival advantage in CSS was seen with obesity (HR 0.69 [95% CI, 0.16-3.03], P = .627). In patients with obesity, HbA1c ≥ 7% independently predicted worse OS (HR 2.36 [95% CI, 1.40-3.98], P < .001).

CONCLUSION

The survival benefit from the obesity paradox in RCC patients appears limited to patients with well-controlled HbA1c. Elevated HbA1c may negate this effect, suggesting optimization of metabolic health and glycemic control may improve outcomes.