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.
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.
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).
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.
Clinical genitourinary cancer. 2025 Oct 14 [Epub ahead of print]
Alexander Abdollahzadeh, Reza Lahiji, Ernest Allen Morton, Lorenzo Storino Ramacciotti, Adam Braunschweig, Dattatraya Patil, Valentina Grajales, Shreyas S Joshi, Vikram M Narayan, Reza Nabavizadeh, Mohammad Hajiha, Kenneth Ogan, Viraj A Master
Department of Urology, Emory University School of Medicine, Atlanta, GA., Department of Urology, Duke Cancer Center, Durham, NC., Department of Urology, Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA. Electronic address: .