{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:52:54Z","timestamp":1780419174269,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Data on locally advanced (LAP) pheochromocytoma\/paraganglioma (PPGL), based on capsular, vascular or periadrenal fat invasion, tumor emboli and extra-adrenal extension, are scarce.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To compare outcomes of patients with LAP and without (nLAP).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Retrospective cohort study, 1981-2024, prospectively supplemented 2020-2024.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Referral center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>Overall, metastatic and nonmetastatic recurrence, overall (OAS) and disease-specific survival (DSS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 283 patients followed for 11.3 \u00b1 8.8 (mean \u00b1 SD) years, 79 (27.9%) had LAP. Compared to patients with nLAP (n = 204), patients with LAP had more overall (n = 17 vs. 31, hazard ratio 2.4, 95% CI 1.4-5.0) and metastatic (11 vs. 9, HR 6.8, 2.2-20.6) and similar (6 vs. 22, HR 1.2, 0.5-3.0) nonmetastatic recurrences. OAS was comparable (12 vs. 42 nonsurvivors, HR 1.2, 0.6-2.3), but mortality from metastatic disease was higher with LAP (2 vs. 4 deaths, HR 12.2, 1.8-82.8). Extra-adrenal tumor location was predictive of metastatic and nonmetastatic recurrence but not of OAS or DSS, tumor size of metastatic recurrence and of DSS, cluster 1 and 2 pathogenic variants of overall and nonmetastatic recurrence but not of OAS or DSS. LAP with tumor emboli and extra-adrenal extension predicted overall (HR 4.5, 1.3-14.2 and 5.0, 1.4-13.7) and metastatic recurrence (HR 24.6, 6.4-91.8 and 6.5, 1.6-23.4), OAS (HR 21.2, 2.8-108, tumor emboli only) and DSS (HR 22.6, 3.5-183 and 13.1, 1.7-120), LAP with vessel invasion nonmetastatic recurrence (HR 3.6, 1.2-10.0).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Patients with LAP vs. nLAP have higher metastatic recurrences and worse DSS. Tumor emboli and extra-adrenal extension indicated lower DSS, warranting a close follow-up.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf104","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T21:43:11Z","timestamp":1747777391000},"page":"705-716","source":"Crossref","is-referenced-by-count":2,"title":["Locally advanced pheochromocytoma\/paraganglioma exhibit high metastatic recurrence and disease specific mortality rates: long-term follow-up of 283 patients"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2289-5696","authenticated-orcid":false,"given":"Wolfgang","family":"Raber","sequence":"first","affiliation":[{"name":"Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Scheuba","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-7455","authenticated-orcid":false,"given":"Harald","family":"Esterbauer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Rohrbeck","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"issue":"2","key":"2025053013414905000_lvaf104-B1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1210\/endrev\/bnab019","article-title":"Personalized management of pheochromocytoma and paraganglioma","volume":"43","author":"N\u00f6lting","year":"2022","journal-title":"Endocr Rev"},{"key":"2025053013414905000_lvaf104-B2","doi-asserted-by":"publisher","first-page":"1419028","DOI":"10.3389\/fendo.2024.1419028","article-title":"Metastatic disease and major adverse cardiovascular events preceding diagnosis are the main determinants of disease-specific survival of pheochromocytoma\/paraganglioma: long-term follow-up of 303 patients","volume":"15","author":"Raber","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2025053013414905000_lvaf104-B3","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s12022-022-09708-2","article-title":"Overview of the 2022 WHO classification of neuroendocrine neoplasms","volume":"33","author":"Rindi","year":"2022","journal-title":"Endocr Pathol"},{"issue":"11","key":"2025053013414905000_lvaf104-B4","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1016\/j.annonc.2020.08.2099","article-title":"Electronic address: clinicalguidelines@esmo.org. 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