JU INSIGHT Diabetes, Obesity, and Pathological Upstaging in Renal Cell Carcinoma

By: Deepak K. Pruthi, MD, MSCI-TS, FRCSC, University of Texas Health San Antonio; Gregor Miller, PhD, Core Facility Statistical Consulting, Helmholtz Mūnchen, Germany; Donna P. Ankerst, PhD, Technical University of Munich, Germany, Munich Data Science Institute, Germany; Matthias Neumair, PhD, Technical University of Munich, Germany; Umberto Capitanio, MD, Urological Research Institute, San Raffaele Hospital, Milan, Italy; Andres F. Correa, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Brian R. Lane, MD, PhD, Spectrum Health Cancer Center, Grand Rapids, Michigan; Eduard Roussel, MD, Katholieke Universiteit Leuven, Belgium; Thomas B. McGregor, MD, FRCSC, Dalhousie University, Halifax, Canada; Ithaar H. Derweesh, MD, University of California San Diego, La Jolla; Mauricio Cordeiro, MD, Universidade de Sao Paolo, Brazil; Phillip M. Pierorazio, MD, Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia; Carlos Calvo, MD, Pontificia Universidad Catolica de Chile, Santiago; Hai Bi, MD, Peking University Third Hospital, Beijing, China; Sabrina L. Noyes, BS, Spectrum Health Cancer Center, Grand Rapids, Michigan; Margaret Meagher, MD, University of California San Diego, La Jolla; Alexander Kutikov, MD, FACS, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Robert G. Uzzo, MD, FACS, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Hendrik Van Poppel, MD, Katholieke Universiteit Leuven, Belgium; Alessandro Larcher, MD, Urological Research Institute, San Raffaele Hospital, Milan, Italy; Francesco Montorsi, MD, Urological Research Institute, San Raffaele Hospital, Milan, Italy; Michael W. Kattan, PhD, MBA, Cleveland Clinic Foundation, Ohio; Dharam Kaushik, MD, University of Texas Health San Antonio; Michael A. Liss, MD, PhD, University of Texas Health San Antonio | Posted on: 27 Nov 2023

Pruthi DK, Miller G, Ankerst DP, et al. Diabetes, obesity, and pathological upstaging in renal cell carcinoma: results from a large multi-institutional consortium. J Urol. 2023;210(5):750-762.

Study Need and Importance

Cancer-specific mortality in renal cell carcinoma (RCC) has remained largely unchanged despite treatment of cT1 tumors. Consequently, there are several promoted strategies in the management of localized tumors including active surveillance. Despite this polarity, after surgical resection many cT1 tumors are upstaged to stage T3a (pT3a), which portends a greater risk of recurrence/metastasis and decreased survival. When counseling patients, we lack accurate preoperative tools to individualize patient risk. By integrating a large (>6000 patients), multi-institutional (11 centers), and multinational (7 countries) cohort, we sought to examine the impact of established clinical risk factors (age, sex, preoperative tumor size) with known metabolic risk factors (hypertension, diabetes, obesity) and tumoral morphometric features in the observation of pathological upstaging (cT1➜pT3a) among those undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 RCC.

What We Found

cT1➜pT3a occurred in 4.9% and 23.3% of the 4092 PN subjects and 2056 RN subjects, respectively. For both groups, upstaging was more likely with increasing preoperative tumor size, increasing age, and diabetes. The effect of diabetes was most pronounced among the RN group (Figure). Among the PN cohort, male sex and increasing BMI were additional risk factors. For all subjects, hilar tumors were more likely to be upstaged. pT3a subtype analysis revealed that diabetes was among the strongest independent risk factors for upstaging.

Figure. Risk curve for pT3a based on the multivariable risk model for radical nephrectomy patients comparing 2 categorical risk factors (sex and diabetes) and as a function of preoperative tumor size.

Limitations

Obtaining systematic protocolized data on recurrence/survival was not possible in this retrospective series. Data on obesity were missing for 8% of subjects in total. The impact of tobacco smoking could not be quantified. Reporting institutions were high-volume referral centers and may consist of higher-risk patients.

Interpretation for Patient Care

While increasing age, tumor size, and male sex remain the backbone of elevated risk for the observation of pathological upstaging in RCC, the presence of diabetes and increasing BMI, and hilar tumor location, further accentuate that risk. Considering these risk factors will aid patients and clinicians in counseling patients for managing clinical T1 renal tumors.