{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:10:06Z","timestamp":1786122606298,"version":"build-2736575974"},"reference-count":12,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020869","name":"AstraZeneca KK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although multigene testing for advanced non\u2010small cell lung cancer (NSCLC) is reimbursed in Japan, optimizing its real\u2010world clinical impact remains challenging. This study updates nationwide testing trends and evaluates the treatment gap between diagnostic results and first\u2010line therapeutic interventions. We conducted a retrospective cohort study using the Diagnosis Procedure Combination database (April 2019 to May 2024). The analysis included 24,047 patients with Stage IV NSCLC across 300 hospitals who underwent diagnostic lung biopsies. Comprehensive multigene testing shifted significantly; testing for \u2265\u20095 genes rose sharply from late 2021, followed by a marked increase in 6\u20137 gene testing from mid\u20102023. Testing for rare drivers (\n                    <jats:italic>MET<\/jats:italic>\n                    ,\n                    <jats:italic>RET<\/jats:italic>\n                    ,\n                    <jats:italic>KRAS<\/jats:italic>\n                    ,\n                    <jats:italic>HER2<\/jats:italic>\n                    ) increased substantially. However, approximately 30% of patients remained untested regardless of region or age. While the proportion of patients receiving first\u2010line targeted therapy plateaued at just under 30%, the use of targeted therapies for rare drivers showed a steady increase. In conclusion, multigene testing has rapidly replaced single\u2010gene testing in Japan, narrowing the diagnostic gap for rare oncogenic drivers. Nevertheless, the persistent 30% untested rate emphasizes the need for better shared decision\u2010making to ensure all patients receive comprehensive biomarker evaluation.\n                  <\/jats:p>","DOI":"10.1111\/cas.70499","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:13:02Z","timestamp":1786101182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Five\u2010Year Trends in Biomarker Testing and Targeted Therapy for\n                    <scp>NSCLC<\/scp>\n                    : A Patient\u2010Initiated Nationwide Survey in Japan"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5203-7911","authenticated-orcid":false,"given":"Satoshi","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology Kansai Medical University  Hirakata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"General Incorporated Association Alliance for Lung Cancer  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Takahama","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Kindai University Faculty of Medicine  Osaka\u2010Sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Kachi","sequence":"additional","affiliation":[{"name":"General Incorporated Association Alliance for Lung Cancer  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"General Incorporated Association Alliance for Lung Cancer  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Kawakami","sequence":"additional","affiliation":[{"name":"General Incorporated Association Alliance for Lung Cancer  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Global Health Consulting Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Sakai","sequence":"additional","affiliation":[{"name":"Global Health Consulting Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Global Health Consulting Japan  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Kindai University Faculty of Medicine  Osaka\u2010Sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"issue":"12","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.47700","article-title":"Biomarker Testing in Patients With Unresectable Advanced or Recurrent Non\u2010Small Cell Lung Cancer","volume":"6","author":"Sakamoto T.","year":"2023","journal-title":"JAMA Network Open"},{"issue":"20","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13205230","article-title":"Oncomine Comprehensive Assay v3 vs. Oncomine Comprehensive Assay Plus","volume":"13","author":"Vestergaard L. K.","year":"2021","journal-title":"Cancers"},{"issue":"3","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/diagnostics11030391","article-title":"Suitability of Bronchoscopic Biopsy Tissue Samples for Next\u2010Generation Sequencing","volume":"11","author":"Murakami S.","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lungcan.2023.107190","article-title":"Clinical Application of the AMOY 9\u2010In\u20101 Panel to Lung Cancer Patients","volume":"179","author":"Kunimasa K.","year":"2023","journal-title":"Lung Cancer"},{"issue":"15","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.3390\/cancers14153784","article-title":"A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens","volume":"14","author":"Morikawa K.","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"21","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","DOI":"10.1002\/cam4.70375","article-title":"Patient\u2010Initiated Nationwide Survey on Testing for Actionable Oncogenic Drivers in Non\u2010Small Cell Lung Cancer in Japan","volume":"13","author":"Ikeda S.","year":"2024","journal-title":"Cancer Medicine"},{"issue":"10","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMoa2004407","article-title":"Tepotinib in Non\u2010Small\u2010Cell Lung Cancer With MET Exon 14 Skipping Mutations","volume":"383","author":"Paik P. K.","year":"2020","journal-title":"New England Journal of Medicine"},{"issue":"10","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1056\/NEJMoa2002787","article-title":"Capmatinib in MET Exon 14\u2010Mutated or MET\u2010Amplified Non\u2010Small\u2010Cell Lung Cancer","volume":"383","author":"Wolf J.","year":"2020","journal-title":"New England Journal of Medicine"},{"issue":"20","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1056\/NEJMoa2309457","article-title":"First\u2010Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion\u2010Positive NSCLC","volume":"389","author":"Zhou C.","year":"2023","journal-title":"New England Journal of Medicine"},{"issue":"10378","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0140-6736(23)00221-0","article-title":"Sotorasib Versus Docetaxel for Previously Treated Non\u2010Small\u2010Cell Lung Cancer With KRASG12C Mutation: A Randomised, Open\u2010Label, Phase 3 Trial","volume":"401","author":"Langen A. J.","year":"2023","journal-title":"Lancet"},{"issue":"31","key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1200\/JCO.23.01361","article-title":"Trastuzumab Deruxtecan in Patients With HER2\u2010Mutant Metastatic Non\u2010Small\u2010Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY\u2010Lung02 Trial","volume":"41","author":"Goto K.","year":"2023","journal-title":"Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in Patients With Advanced or Metastatic NTRK Fusion\u2010Positive Solid Tumours: Integrated Analysis of Three Phase 1\u20102 Trials","volume":"21","author":"Doebele R. C.","year":"2020","journal-title":"Lancet Oncology"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70499","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70499","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:13:04Z","timestamp":1786101184000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":12,"alternative-id":["10.1111\/cas.70499"],"URL":"https:\/\/doi.org\/10.1111\/cas.70499","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"2026-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cas.70499"}}