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

IF 2.4 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI:10.1016/j.clgc.2025.102457

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

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Abstract

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.

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糖化血红蛋白对非转移性肾癌患者肥胖悖论和生存的影响

“肥胖悖论”表明，包括肾细胞癌（RCC）和身体质量指数(BMI)≥30 kg/m2的各种癌症患者可能会改善生存。然而，血糖控制对这种关联的影响尚不清楚。本研究评估了在非转移性肾细胞癌患者行肾切除术时，HbA1c升高是否会改变与肥胖悖论相关的生存获益。方法对2005年至2024年在单一学术中心接受非转移性肾细胞癌肾切除术的患者进行筛选。纳入标准包括术前3个月内测量的HbA1c和随访≥6个月。肥胖定义为BMI≥30 kg/m²；HbA1c升高≥7%。采用Cox比例风险模型和Kaplan-Meier分析评估总生存期（OS）和癌症特异性生存期（CSS）。结果770例患者符合纳入标准。中位随访时间为45.2个月；发生了172例（22%）死亡事件。在HbA1c和lt为7%的患者中，在控制混杂因素后，肥胖患者的CSS比非肥胖患者有所改善（HR 0.21 [95% CI, 0.09-0.48], P < 0.001）。在HbA1c≥7%的患者中，肥胖的CSS患者没有明显的生存优势（HR 0.69 [95% CI, 0.16-3.03], P = .627）。在肥胖患者中，HbA1c≥7%独立预测较差的OS （HR 2.36 [95% CI, 1.40-3.98], P < 0.001）。结论肥胖悖论对RCC患者的生存益处似乎仅限于控制良好的HbA1c患者。升高的HbA1c可能会抵消这种作用，这表明优化代谢健康和血糖控制可能会改善结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.