{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:13:47Z","timestamp":1788970427370,"version":"build-2803163510"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal metastasis of unknown primary at the initial visit represents a clinically important subset of metastatic bone tumours, accounting for ~7.8%\u201321.7% of all skeletal metastases. This condition differs from cancer of unknown primary (CUP), in which the primary site remains unidentified after comprehensive evaluation. At this diagnostic entry point, before completion of a full work-up, early stratification is essential; however, the clinical utility of serum tumour markers at this stage remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed 79 patients who presented with skeletal metastasis of unknown primary at the initial visit before diagnostic work-up between January 2010 and October 2023. Clinical characteristics, final primary diagnoses, types of tumour markers measured, positivity rates, and diagnostic performance were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Haematologic malignancies were the most frequent final diagnoses (40.5%), followed by lung (22.8%) and prostate cancer (10.1%). A total of 17 tumour markers were measured (mean, 6.3 per patient; range, 0\u201312). Prostate-specific antigen (PSA), immunoelectrophoresis (IEP), soluble interleukin-2 receptor (sIL-2R), and thyroglobulin (Tg) showed high sensitivity and specificity for prostate cancer, multiple myeloma, malignant lymphoma, and thyroid cancer, respectively. Carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19, CYFRA 21-1), although not organ-specific, were frequently positive in carcinomas and served as indicators of epithelial malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum tumour markers can assist early diagnostic stratification at the initial presentation of skeletal metastasis before primary-site identification. A selective testing strategy focusing on sIL-2R, IEP, CEA, and CK19, with PSA added in men and Tg when clinically indicated, may improve diagnostic efficiency and provide a basis for considering a bone-metastasis-oriented diagnostic approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyag074","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:30:35Z","timestamp":1776771035000},"page":"1097-1102","source":"Crossref","is-referenced-by-count":0,"title":["Clinical utility of tumour markers in skeletal metastasis of unknown primary at the initial visit"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-8532","authenticated-orcid":false,"given":"Kensaku","family":"Yamaga","sequence":"first","affiliation":[{"name":"Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University , 36-1 Nishi-cho, Yonago 683-8504 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Akahori","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University , 36-1 Nishi-cho, Yonago 683-8504 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Osaki","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University , 36-1 Nishi-cho, Yonago 683-8504 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University , 36-1 Nishi-cho, Yonago 683-8504 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"2026090910440908100_ref1","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.3390\/cancers11091270","article-title":"Skeletal metastases of unknown primary: biological landscape and clinical overview","volume":"11","author":"Argentiero","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2026090910440908100_ref2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129428","article-title":"Skeletal metastasis of unknown primary origin at the initial visit: a retrospective analysis of 286 cases","volume":"10","author":"Takagi","year":"2015","journal-title":"PloS One"},{"key":"2026090910440908100_ref3","doi-asserted-by":"publisher","DOI":"10.52965\/001c.123441","article-title":"Diagnostic approach to bone metastasis of unknown origin: a systematic review","volume":"16","author":"Putro","year":"2024","journal-title":"Orthop Rev (Pavia)"},{"key":"2026090910440908100_ref4","doi-asserted-by":"publisher","DOI":"10.1177\/20503121221097582","article-title":"Effective examination methods for identifying the primary origins of metastatic bone tumors of unknown primary origin during the initial visit: a retrospective chart review study","volume":"10","author":"Fujibuchi","year":"2022","journal-title":"SAGE Open Med"},{"key":"2026090910440908100_ref5","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/(SICI)1097-0142(19990801)86:3&lt;533::AID-CNCR24&gt;3.0.CO;2-1","article-title":"Determining the site of the primary cancer in patients with skeletal metastasis of unknown origin: a retrospective study","volume":"86","author":"Katagiri","year":"1999","journal-title":"Cancer."},{"key":"2026090910440908100_ref6","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s10195-015-0344-0","article-title":"Bone metastases of unknown origin: epidemiology and principles of management","volume":"16","author":"Piccioli","year":"2015","journal-title":"J Orthop Traumatol"},{"key":"2026090910440908100_ref7","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jbspin.2006.05.009","article-title":"Investigations for bone metastasis from an unknown primary","volume":"74","author":"Destombe","year":"2007","journal-title":"Joint Bone Spine"},{"key":"2026090910440908100_ref8","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1007\/s00586-009-1061-2","article-title":"Diagnosis of a previously unidentified primary site in patients with spinal metastasis: diagnostic usefulness of laboratory analysis, CT scanning and CT-guided biopsy","volume":"18","author":"Iizuka","year":"2009","journal-title":"Eur Spine J"},{"key":"2026090910440908100_ref9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.2214\/AJR.22.27842","article-title":"CT-guided core needle biopsy of nonspinal bone lesions: comparison of occult and visible bone lesions","volume":"220","author":"Kim","year":"2023","journal-title":"AJR Am J Roentgenol"},{"key":"2026090910440908100_ref10","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40644-019-0230-8","article-title":"Value of CT-guided percutaneous needle biopsy of bone in the diagnosis of lymphomas based on PET\/CT results","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Imaging"},{"key":"2026090910440908100_ref11","first-page":"4164","article-title":"The incidence and mortality trends of bone lymphoma in the United States: SEER analysis of 1975\u20132016","volume":"9","author":"Xu","year":"2020","journal-title":"Cancer Med"},{"key":"2026090910440908100_ref12","doi-asserted-by":"publisher","first-page":"92","DOI":"10.5045\/kjh.2012.47.2.92","article-title":"Epidemiologic overview of malignant lymphoma","volume":"47","author":"Huh","year":"2012","journal-title":"Korean J Hematol"},{"key":"2026090910440908100_ref13","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3346\/jkms.2014.29.3.357","article-title":"Non-spine bone metastasis as an initial manifestation of cancer in Korea","volume":"29","author":"Kim","year":"2014","journal-title":"J Korean Med Sci"},{"key":"2026090910440908100_ref14","first-page":"15","article-title":"Skeletal metastases of unknown origin: a retrospective analysis of 29 cases","volume":"63","author":"Jacobsen","year":"1997","journal-title":"Acta Orthop Belg"},{"key":"2026090910440908100_ref15","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.2106\/00004623-199309000-00003","article-title":"Skeletal metastases of unknown origin: a prospective study of a diagnostic strategy","volume":"75","author":"Rougraff","year":"1993","journal-title":"J Bone Joint Surg Am"},{"key":"2026090910440908100_ref16","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1002\/cncr.20202","article-title":"Diagnostic strategies for unknown primary cancer","volume":"100","author":"Varadhachary","year":"2004","journal-title":"Cancer."},{"key":"2026090910440908100_ref17","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1016\/S0959-8049(03)00547-1","article-title":"Diagnostic and therapeutic management of cancer of an unknown primary","volume":"39","author":"Pavlidis","year":"2003","journal-title":"Eur J Cancer"},{"key":"2026090910440908100_ref18","article-title":"National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: occult primary (Cancer of Unknown Primary [CUP])","year":"2016"},{"key":"2026090910440908100_ref19","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1056\/NEJMra1303917","article-title":"Cancer of unknown primary site","volume":"371","author":"Varadhachary","year":"2014","journal-title":"N Engl J Med"},{"key":"2026090910440908100_ref20","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1634\/theoncologist.2-3-142","article-title":"Cancer of unknown primary origin","volume":"2","author":"Briasoulis","year":"1997","journal-title":"Oncologist."},{"key":"2026090910440908100_ref21","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nrclinonc.2011.158","article-title":"Carcinomas of an unknown primary origin: diagnosis and treatment","volume":"8","author":"Massard","year":"2011","journal-title":"Nat Rev Clin Oncol"},{"key":"2026090910440908100_ref22","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.1373\/clinchem.2008.105601","article-title":"National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers","volume":"54","author":"Sturgeon","year":"2008","journal-title":"Clin Chem"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/9\/1097\/68271107\/hyag074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/9\/1097\/68271107\/hyag074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:29:59Z","timestamp":1788967799000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/56\/9\/1097\/8676262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5,12]]},"published-print":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyag074","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,5,12]]}}}