{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:40:16Z","timestamp":1792395616898,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Surgical Oncology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Recurrence risk after hepatectomy for colorectal liver metastases (CRLMs) changes during follow\u2010up, but whether baseline tumor burden remains prognostically relevant with increasing recurrence\u2010free time is unclear. We evaluated the time\u2010dependent prognostic relevance of liver metastasis number.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 226 patients who underwent initial curative\u2010intent hepatectomy for CRLMs between 2007 and 2022. Three\u2010year conditional recurrence\u2010free survival (RFS) was estimated at surgery and after 6, 12, and 24 months without recurrence. Landmark Cox models evaluated liver metastasis number (&lt;\u20094 vs. \u2265\u20094), adjusting for\n                      <jats:italic>RAS<\/jats:italic>\n                      status, with supplementary expanded models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three\u2010year conditional RFS improved from 27.1% at surgery to 33.3%, 49.3%, and 76.6% after 6, 12, and 24 months without recurrence, respectively. However, subsequent RFS remained worse in patients with \u2265\u20094 liver metastases at the 6\u2010month (adjusted hazard ratio [HR]: 1.83, 95% confidence interval [CI]: 1.14\u20132.94;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012) and 12\u2010month (HR: 2.14, 95% CI: 1.08\u20134.27;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030) landmarks. In supplementary expanded models, the associations remained directionally similar but were attenuated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Recurrence risk improved with increasing recurrence\u2010free time, but survivors remained heterogeneous according to baseline tumor burden. Liver metastasis number retained prognostic relevance at early postoperative landmarks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jso.70428","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:50:05Z","timestamp":1792392605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conditional Recurrence\u2010Free Survival After Hepatectomy for Colorectal Liver Metastases: Time\u2010Dependent Prognostic Relevance of Liver Metastasis Number"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3619-6362","authenticated-orcid":false,"given":"Taiki","family":"Mori","sequence":"first","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-0652","authenticated-orcid":false,"given":"Nozomu","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-1942","authenticated-orcid":false,"given":"Tsukasa","family":"Takayashiki","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6495-0422","authenticated-orcid":false,"given":"Shigetsugu","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isamu","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-8313","authenticated-orcid":false,"given":"Takanori","family":"Konishi","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-7502","authenticated-orcid":false,"given":"Hitoe","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Nakada","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5091-1078","authenticated-orcid":false,"given":"Masayuki","family":"Ohtsuka","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"issue":"1","key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jhbp.868","article-title":"Clinical Practice Guidelines for the Management of Liver Metastases From Extrahepatic Primary Cancers 2021","volume":"28","author":"Yamamoto M.","year":"2021","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"6","key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/00000658-200206000-00002","article-title":"Trends in Long\u2010Term Survival Following Liver Resection for Hepatic Colorectal Metastases","volume":"235","author":"Choti M. A.","year":"2002","journal-title":"Annals of Surgery"},{"issue":"29","key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1200\/JCO.2007.11.0833","article-title":"Actual 10\u2010year Survival After Resection of Colorectal Liver Metastases Defines Cure","volume":"25","author":"Tomlinson J. S.","year":"2007","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_14_5_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2022.102382","article-title":"The Management of Colorectal Liver Metastases Amenable of Surgical Resection: How to Shape Treatment Strategies According to Clinical, Radiological, Pathological and Molecular Features","volume":"106","author":"Germani M. M.","year":"2022","journal-title":"Cancer Treatment Reviews"},{"issue":"3","key":"e_1_2_14_6_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/SLA.0b013e3181b4539b","article-title":"Rates and Patterns of Recurrence Following Curative Intent Surgery for Colorectal Liver Metastasis: An International Multi\u2010Institutional Analysis of 1669 Patients","volume":"250","author":"Jong M. C.","year":"2009","journal-title":"Annals of Surgery"},{"issue":"4","key":"e_1_2_14_7_1","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1245\/s10434-010-1409-1","article-title":"Effect on Outcome of Recurrence Patterns After Hepatectomy for Colorectal Metastases","volume":"18","author":"D'Angelica M.","year":"2011","journal-title":"Annals of Surgical Oncology"},{"issue":"6","key":"e_1_2_14_8_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/jhbp.964","article-title":"Risk Stratification and Goal of Systemic Therapy for Successful Surgical Management of Colorectal Liver Metastases: Oncological Optimization","volume":"28","author":"Shindoh J.","year":"2021","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"3","key":"e_1_2_14_9_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/00000658-199909000-00004","article-title":"Clinical Score for Predicting Recurrence After Hepatic Resection for Metastatic Colorectal Cancer: Analysis of 1001 Consecutive Cases","volume":"230","author":"Fong Y.","year":"1999","journal-title":"Annals of Surgery"},{"issue":"7","key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1002\/(SICI)1097-0142(19960401)77:7<1254::AID-CNCR5>3.0.CO;2-I","article-title":"Surgical Resection of Colorectal Carcinoma Metastases to the Liver: A Prognostic Scoring System to Improve Case Selection, Based on 1568 Patients","volume":"77","author":"Nordlinger B.","year":"1996","journal-title":"Cancer"},{"issue":"1","key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/SLA.0b013e31815aa2c2","article-title":"Evaluation of Long\u2010Term Survival After Hepatic Resection for Metastatic Colorectal Cancer: A Multifactorial Model of 929 Patients","volume":"247","author":"Rees M.","year":"2008","journal-title":"Annals of Surgery"},{"issue":"4","key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/SLA.0b013e3182a5025a","article-title":"RAS Mutation Status Predicts Survival and Patterns of Recurrence in Patients Undergoing Hepatectomy for Colorectal Liver Metastases","volume":"258","author":"Vauthey J. N.","year":"2013","journal-title":"Annals of Surgery"},{"issue":"5","key":"e_1_2_14_13_1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/jhbp.1252","article-title":"Comprehensive Data of 4502 Patients Newly Diagnosed With Colorectal Liver Metastasis Between 2015 and 2017, and Prognostic Data of 2427 Patients Newly Diagnosed With Colorectal Liver Metastasis in 2013 and 2014: Third Report of a Nationwide Survey in Japan","volume":"30","author":"Sakamoto K.","year":"2023","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"2","key":"e_1_2_14_14_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/jhbp.1389","article-title":"RAS Mutation Status in Combination With the JSHBPS Nomogram May Be Useful for Preoperative Identification of Colorectal Liver Metastases With High Risk of Recurrence and Mortality After Hepatectomy","volume":"31","author":"Takematsu T.","year":"2024","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"11","key":"e_1_2_14_15_1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/jhbp.810","article-title":"Long\u2010Term Outcome of Liver Resection for Colorectal Metastases in the Presence of Extrahepatic Disease: A Multi\u2010Institutional Japanese Study","volume":"27","author":"Sawada Y.","year":"2020","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"3","key":"e_1_2_14_16_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jamcollsurg.2019.04.027","article-title":"Conditional Recurrence\u2010Free Survival After Resection of Colorectal Liver Metastases: Persistent Deleterious Association With RAS and TP53 Co\u2010mutation","volume":"229","author":"Kawaguchi Y.","year":"2019","journal-title":"Journal of the American College of Surgeons"},{"issue":"6","key":"e_1_2_14_17_1","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1245\/s10434-023-13189-w","article-title":"Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results From the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC)","volume":"30","author":"Valenzuela C. D.","year":"2023","journal-title":"Annals of Surgical Oncology"},{"issue":"12","key":"e_1_2_14_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejso.2023.107103","article-title":"Follow Up After Surgery for Colorectal Liver Metastases: A Systematic Review","volume":"49","author":"Jones A.","year":"2023","journal-title":"European Journal of Surgical Oncology"},{"issue":"11","key":"e_1_2_14_19_1","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.6004\/jnccn.2020.7596","article-title":"A New Surveillance Algorithm After Resection of Colorectal Liver Metastases Based on Changes in Recurrence Risk and RAS Mutation Status","volume":"18","author":"Kawaguchi Y.","year":"2020","journal-title":"Journal of the National Comprehensive Cancer Network"},{"issue":"9","key":"e_1_2_14_20_1","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1111\/ans.17835","article-title":"Recurrence Patterns Predict Survival After Resection of Colorectal Liver Metastases","volume":"92","author":"Wong G. Y. M.","year":"2022","journal-title":"ANZ Journal of Surgery"},{"issue":"4","key":"e_1_2_14_21_1","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1245\/s10434-023-14806-4","article-title":"Local Therapy Improves Survival for Early Recurrence After Resection of Colorectal Liver Metastases","volume":"31","author":"Boyev A.","year":"2024","journal-title":"Annals of Surgical Oncology"},{"issue":"2","key":"e_1_2_14_22_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.surg.2015.09.003","article-title":"Survival Benefit of Repeat Resection of Successive Recurrences After the Initial Hepatic Resection for Colorectal Liver Metastases","volume":"159","author":"Oba M.","year":"2016","journal-title":"Surgery"},{"issue":"8","key":"e_1_2_14_23_1","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1245\/s10434-015-4370-1","article-title":"Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection","volume":"22","author":"Butte J. M.","year":"2015","journal-title":"Annals of Surgical Oncology"},{"issue":"3","key":"e_1_2_14_24_1","doi-asserted-by":"crossref","first-page":"znaf003","DOI":"10.1093\/bjs\/znaf003","article-title":"Recurrence Patterns and Post\u2010Recurrence Survival of Patients With Bilobar Colorectal Liver Metastases: International Multicentre Retrospective Study","volume":"112","author":"Bilobar CRC Liver Metastases Research Collaborative","year":"2025","journal-title":"British Journal of Surgery"},{"issue":"10","key":"e_1_2_14_25_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/hpb.12136","article-title":"Prognostic Significance of Early Recurrence: A Conditional Survival Analysis in Patients With Resected Colorectal Liver Metastasis","volume":"15","author":"Tan M. C. B.","year":"2013","journal-title":"HPB: Official Journal of the International Hepato\u2010Pancreato\u2010Biliary Association"},{"issue":"1","key":"e_1_2_14_26_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s00534-011-0460-z","article-title":"A Nomogram Predicting Disease\u2010Free Survival in Patients With Colorectal Liver Metastases Treated With Hepatic Resection: Multicenter Data Collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato\u2010Biliary\u2010Pancreatic Surgery","volume":"19","author":"Beppu T.","year":"2012","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"3","key":"e_1_2_14_27_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/jhbp.58","article-title":"Optimal Cut\u2010Off Value for the Number of Colorectal Liver Metastases: A Project Study for Hepatic Surgery of the Japanese Society of Hepato\u2010Biliary\u2010Pancreatic Surgery","volume":"21","author":"Beppu T.","year":"2014","journal-title":"Journal of Hepato\u2010Biliary\u2010Pancreatic Sciences"},{"issue":"8","key":"e_1_2_14_28_1","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1245\/s10434-018-6517-3","article-title":"RAS Mutation is Associated With Unsalvageable Recurrence Following Hepatectomy for Colorectal Cancer Liver Metastases","volume":"25","author":"Okuno M.","year":"2018","journal-title":"Annals of Surgical Oncology"},{"issue":"1","key":"e_1_2_14_29_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1186\/s12885-021-08144-5","article-title":"Differential Effects of KRAS Mutational Status on Long\u2010Term Survival According to the Timing of Colorectal Liver Metastases","volume":"21","author":"Sakai N.","year":"2021","journal-title":"BMC Cancer"},{"issue":"10","key":"e_1_2_14_30_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/S1470-2045(22)00506-X","article-title":"Recurrence\u2010Free Survival Versus Overall Survival as a Primary Endpoint for Studies of Resected Colorectal Liver Metastasis: A Retrospective Study and Meta\u2010Analysis","volume":"23","author":"Ecker B. L.","year":"2022","journal-title":"Lancet Oncology"},{"issue":"1","key":"e_1_2_14_31_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1186\/s12885-024-12162-4","article-title":"Prognostic Factors Associated With Early Recurrence Following Liver Resection for Colorectal Liver Metastases: A Systematic Review and Meta\u2010Analysis","volume":"24","author":"Tian Y.","year":"2024","journal-title":"BMC Cancer"},{"issue":"1","key":"e_1_2_14_32_1","doi-asserted-by":"crossref","DOI":"10.1177\/1073274818789355","article-title":"Immortal Time Bias in Observational Studies of Time\u2010To\u2010Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database","volume":"25","author":"Agarwal P.","year":"2018","journal-title":"Cancer Control"}],"container-title":["Journal of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70428","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jso.70428","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:50:09Z","timestamp":1792392609000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jso.70428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,18]]},"references-count":31,"alternative-id":["10.1002\/jso.70428"],"URL":"https:\/\/doi.org\/10.1002\/jso.70428","archive":["Portico"],"relation":{},"ISSN":["0022-4790","1096-9098"],"issn-type":[{"value":"0022-4790","type":"print"},{"value":"1096-9098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,18]]},"assertion":[{"value":"2026-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jso.70428"}}