{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:30:31Z","timestamp":1786707031894,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: The \u201cobesity paradox\u201d describes the observed association between improved cancer-specific (CSS) and overall (OS) survival observed among obese (BMI \u2265 30 kg\/m2) patients with RCC. Prior studies have reported lower stage\/grade tumors among obese patients to explain this. This study aimed to evaluate subcutaneous (SFA) and visceral fat area (VFA) associations with CSS, OS, tumor stage and grade among patients with non-metastatic clear cell RCC. Methods: Following IRB approval, patients undergoing nephrectomy for clear cell RCC between 2000 and 2023 were screened for inclusion. Eligible patients were those with non-metastatic disease and available preoperative imaging within 90 days of surgery. SFA and VFA were determined using mid-L3 imaging and standardized Hounsfield Unit thresholds. Multivariable Cox models evaluated factors associated with 5-year CSS and OS, and multivariable logistic regression models evaluated associations with pathologic stage (pT) 3\u20134 and Fuhrman grade 3\u20134 disease. Results: 400 patients were included. Higher SFA quartiles were independently associated with improved CSS (Q3 HR 0.21, p = 0.029; Q4 HR 0.24, p = 0.042) and OS (Q2-Q4 HR range 0.35\u20130.52, all p &lt; 0.05) compared to Q1. VFA was not independently associated with OS and showed only an isolated association with CSS in the third quartile (HR 2.95, p = 0.041). Neither SFA nor VFA were independently associated with RCC stage or grade. Conclusions: Greater subcutaneous adiposity was associated with improved 5-year CSS\/OS, whereas visceral adiposity did not demonstrate consistent associations with survival outcomes. These findings refine the obesity paradox and reflect the importance of fat distribution as a more specific risk factor than weight-based measures such as BMI alone.<\/jats:p>","DOI":"10.3390\/cancers18162626","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"2626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subcutaneous Fat Is Associated with Improved Survival in Patients with Non-Metastatic Clear Cell Renal Cell Carcinoma: Dissecting the Obesity Paradox"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3205-3944","authenticated-orcid":false,"given":"Reza","family":"Lahiji","sequence":"first","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mumford","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N.","family":"Schmeusser","sequence":"additional","affiliation":[{"name":"Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2940-4917","authenticated-orcid":false,"given":"Gloria","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0250-4005","authenticated-orcid":false,"given":"Charan","family":"Koltur","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Esen","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"},{"name":"Department of Urology, Koc University School of Medicine, Istanbul 34450, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo Storino","family":"Ramacciotti","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Luke","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2130-7748","authenticated-orcid":false,"given":"Pooja","family":"Hemige","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Grajales","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram N.","family":"Narayan","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Nabavizadeh","sequence":"additional","affiliation":[{"name":"Department of Urology, Duke Cancer Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Hajiha","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreyas S.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-7636","authenticated-orcid":false,"given":"Nazih","family":"Khater","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-7490","authenticated-orcid":false,"given":"Sarah P.","family":"Psutka","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Ogan","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viraj A.","family":"Master","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, 1365 Clifton Road NE, Building B, Suite 1400, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0140-6736(08)60269-X","article-title":"Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies","volume":"371","author":"Renehan","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1464-410X.2009.08706.x","article-title":"Obesity is associated with a higher risk of clear-cell renal cell carcinoma than with other histologies","volume":"105","author":"Lowrance","year":"2010","journal-title":"BJU Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.juro.2013.04.130","article-title":"Risk factors for renal cell carcinoma in the VITAL study","volume":"190","author":"Macleod","year":"2013","journal-title":"J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/JU.0000000000001377","article-title":"A systematic review and Meta-analysis of the significance of body mass index on kidney cancer outcomes","volume":"205","author":"Kim","year":"2021","journal-title":"J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.euros.2022.03.002","article-title":"Impact of body mass index on survival outcomes of patients with metastatic renal cell carcinoma in the immuno-oncology era: A systematic review and meta-analysis","volume":"39","author":"Takemura","year":"2022","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_6","first-page":"387","article-title":"Obesity: A major component of the metabolic syndrome","volume":"32","author":"Nesto","year":"2005","journal-title":"Tex. Heart Inst. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shetty, S., Suvarna, R., Bhattacharya, S., and Seetharaman, K. (2025). Visceral adiposity and cardiometabolic risk: Clinical insights and assessment. Cardiol. Rev.","DOI":"10.1097\/CRD.0000000000000984"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102457","DOI":"10.1016\/j.clgc.2025.102457","article-title":"Impact of hemoglobin A1c on the obesity paradox and survival in patients with non-metastatic renal cell carcinoma","volume":"23","author":"Abdollahzadeh","year":"2025","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S1470-2045(19)30797-1","article-title":"Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: A cohort study","volume":"21","author":"Sanchez","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e70014","DOI":"10.1002\/rco2.70014","article-title":"Sarcopenia thresholds derived from healthy adult populations predict survival in patients with cancer","volume":"8","author":"Lahiji","year":"2025","journal-title":"JCSM Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.juro.2014.11.088","article-title":"Mortality after Radical Cystectomy: Impact of Obesity Versus Adiposity after Adjusting for Skeletal Muscle Wasting","volume":"193","author":"Psutka","year":"2015","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Callahan, E.A. (2023). The Science, Strengths, and Limitations of Body Mass Index. Translating Knowledge of Foundational Drivers of Obesity into Practice: Proceedings of a Workshop Series, National Academies Press (US).","DOI":"10.17226\/26942"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Steele, S., Lin, F., Le, T.L., Medline, A., Higgins, M., Sandberg, A., Evans, S., Hong, G., Williams, M.A., and Bilen, M.A. (2021). Segmentation and linear measurement for body composition analysis using slice-O-matic and Horos. J. Vis. Exp.","DOI":"10.3791\/61674"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11934-023-01157-6","article-title":"Imaging techniques to determine degree of sarcopenia and systemic inflammation in advanced renal cell carcinoma","volume":"24","author":"Schmeusser","year":"2023","journal-title":"Curr. Urol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2147\/CMAR.S526583","article-title":"Clinicopathological features and prognostic factors of renal cell carcinoma in young patients under 45 years: A single-center retrospective study","volume":"17","author":"Gao","year":"2025","journal-title":"Cancer Manag. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/bjc.2017.149","article-title":"Subcutaneous adiposity is an independent predictor of mortality in cancer patients","volume":"117","author":"Ebadi","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R207","DOI":"10.1530\/ERC-20-0457","article-title":"Renal cell carcinoma (RCC): Fatter is better? A review on the role of obesity in RCC","volume":"28","author":"Turco","year":"2021","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20200334","DOI":"10.1259\/bjr.20200334","article-title":"Increased visceral adipose tissue in clear cell renal cell carcinoma with and without peritumoral collateral vessels","volume":"93","author":"Greco","year":"2020","journal-title":"Br. J. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1590\/S1677-5538.IBJU.2015.0396","article-title":"Renal Cell Carcinoma and Visceral Adipose Index: A new risk parameter","volume":"42","author":"Otunctemur","year":"2016","journal-title":"Int. Braz. J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/bju.12592","article-title":"Visceral fat accumulation is associated with different pathological subtypes of renal cell carcinoma (RCC): A multicentre study in China: Visceral fat levels associated with different pathological subtypes of RCC","volume":"114","author":"Wang","year":"2014","journal-title":"BJU Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6147426","DOI":"10.1155\/2018\/6147426","article-title":"Osteosarcopenic visceral obesity and osteosarcopenic subcutaneous obesity, two new phenotypes of sarcopenia: Prevalence, metabolic profile, and risk factors","volume":"2018","author":"Perna","year":"2018","journal-title":"J. Aging Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alalwan, T.A. (2020). Phenotypes of sarcopenic obesity: Exploring the effects on Peri-muscular fat, the obesity paradox, hormone-related responses and the clinical implications. Geriatrics, 5.","DOI":"10.3390\/geriatrics5010008"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Berardi, E., Madaro, L., Lozanoska-Ochser, B., Adamo, S., Thorrez, L., Bouche, M., and Coletti, D. (2021). A pound of flesh: What cachexia is and what it is not. Diagnostics, 11.","DOI":"10.3390\/diagnostics11010116"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.1016\/j.clnu.2021.08.003","article-title":"Subcutaneous, but not visceral, adipose tissue as a marker for prognosis in gastric cancer patients with cachexia","volume":"40","author":"Han","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_25","first-page":"1","article-title":"Fat loss in cachexia--is. there a role for adipocyte lipolysis?","volume":"26","author":"Arner","year":"2007","journal-title":"Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15330338241307686","DOI":"10.1177\/15330338241307686","article-title":"Machine learning-based pathomics model to predict the prognosis in clear cell renal cell carcinoma","volume":"23","author":"Li","year":"2024","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41746-025-02034-x","article-title":"A multimodal AI model for precision prognosis in clear cell renal cell carcinoma: A multicenter study","volume":"8","author":"Zang","year":"2025","journal-title":"npj Digit. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.22465\/juo.234600500025","article-title":"Influence of body composition on the perioperative and survival outcomes of renal cell carcinoma","volume":"21","author":"Nicaise","year":"2023","journal-title":"J. Urol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.clnu.2021.11.012","article-title":"Skeletal muscle radiodensity and visceral adipose tissue index are associated with survival in renal cell cancer\u2014A multicenter population-based cohort study","volume":"41","author":"Maurits","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/jjco\/hyu193","article-title":"Visceral obesity is associated with better recurrence-free survival after curative surgery for Japanese patients with localized clear cell renal cell carcinoma","volume":"45","author":"Kaneko","year":"2015","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E675","DOI":"10.5489\/cuaj.1979","article-title":"Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma","volume":"8","author":"Mano","year":"2014","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/jcsm.13429","article-title":"Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer","volume":"15","author":"Furberg","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:45:32Z","timestamp":1786704332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":32,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162626"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162626","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}