{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T09:18:29Z","timestamp":1783588709177,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"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>Background: Obesity has evolved from a morphometric descriptor to a chronic, relapsing, multisystem disease in which low-grade adipose-tissue inflammation, insulin resistance, endothelial dysfunction, and a prothrombotic, pro-tumorigenic milieu coexist. Venous thromboembolism (VTE) and malignancy share this substrate through a well-established bidirectional link: within twelve months of an unprovoked deep vein thrombosis (DVT), 6\u201315% of patients are diagnosed with occult cancer, a substantial proportion of which are already locally advanced or metastatic at detection. In this context, obesity acts as a dual amplifier of both thrombotic and oncologic risk, making the post-DVT patient with an incidentally diagnosed cancer a paradigmatic candidate for integrated management. Objective: To propose an evidence-based, unifying cardiometabolic and antithrombotic clinical framework that reconciles (i) risk-stratified screening for occult malignancy after unprovoked DVT, (ii) contemporary pharmacotherapy of obesity, and (iii) cancer-associated thrombosis (CAT) management, in the light of evidence published through 2025. Methods: Narrative synthesis based on a structured literature search (PubMed\/MEDLINE, Embase, Scopus; 2000\u2013March 2025) of current guidelines (ISTH, ASH, ESC Cardio-Oncology, EASO) and pivotal randomized evidence on GLP-1 and dual GLP-1\/GIP receptor agonists (semaglutide, tirzepatide), SGLT2 inhibitors (empagliflozin, dapagliflozin), and direct oral anticoagulants (DOACs), with critical interpretation of recent meta-analytic data on oncologic signals, cardiovascular outcomes, and bleeding safety. Results: Three evidence-based pillars emerge: (1) limited screening complemented by age- and sex-specific testing in patients \u2265 50 years with unprovoked DVT, enhanced by FDG-PET\/CT for high-risk phenotypes in which obesity itself degrades the sensitivity of clinical examination and conventional imaging; (2) GLP-1\/GIP receptor agonist-based anti-obesity pharmacotherapy, associated in observational cohorts with a 17% relative reduction in overall cancer incidence (HR 0.83; 95% CI 0.76\u20130.91) and neutral-to-reassuring oncologic signals, but requiring cautious, case-by-case use in patients with active cancer because of the risk of accelerating sarcopenia and cachexia; and (3) apixaban as the preferred DOAC for cancer-associated thrombosis, with a superior efficacy-to-bleeding ratio in network meta-analyses and a reduced-dose extended strategy now validated by the API-CAT trial. Conclusions: Patients with obesity presenting with unprovoked DVT and an incidentally detected cancer embody a cardiometabolic\u2013antithrombotic continuum. A framework integrating structured occult-cancer screening, judicious obesity pharmacotherapy, and apixaban-preferred anticoagulation\u2014coordinated by a multidisciplinary team and illustrated here by a case-based pathway\u2014offers the most rational, evidence-aligned approach. Prospective, dedicated trials in this specific phenotype are urgently warranted.<\/jats:p>","DOI":"10.3390\/cancers18142212","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:50:56Z","timestamp":1783587056000},"page":"2212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Holistic Management of Obesity in Patients with Incidental Cancer After Unprovoked Deep Vein Thrombosis: A Cardiometabolic and Antithrombotic Framework"],"prefix":"10.3390","volume":"18","author":[{"given":"Calogero","family":"Geraci","sequence":"first","affiliation":[{"name":"Cardio Obesity Group, ACRIS ETS APS\u2014Associazione Cuore Rene Ipertensione Sicilia, 93017 Caltanissetta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-8487","authenticated-orcid":false,"given":"Rossella","family":"Cannarella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Morello","sequence":"additional","affiliation":[{"name":"Cardio Obesity Group, ACRIS ETS APS\u2014Associazione Cuore Rene Ipertensione Sicilia, 93017 Caltanissetta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Patern\u00f2","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Giovanni Paolo II Hospital, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore Massimo","family":"Petrina","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Giovanni Paolo II Hospital, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-7152","authenticated-orcid":false,"given":"Roberta","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-1151","authenticated-orcid":false,"given":"Giulio","family":"Geraci","sequence":"additional","affiliation":[{"name":"University of Unikore, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-9343","authenticated-orcid":false,"given":"Rosita A.","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-2372","authenticated-orcid":false,"given":"Sandro","family":"La Vignera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-335X","authenticated-orcid":false,"given":"Aldo E.","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2024). 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