{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:10:00Z","timestamp":1792271400109,"version":"4.4.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>To evaluate the primary resistance factors to enfortumab vedotin (EV) monotherapy by comparing treatment outcomes between the early progressive disease (EPD) group and non-EPD group.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We retrospectively analyzed 121 patients with advanced urothelial carcinoma who received EV monotherapy across five institutions between 2019 and 2024. The patients were categorized into the EPD group (<jats:italic>n<\/jats:italic>\u2009=\u200934), defined by radiologically confirmed progressive disease within 3\u00a0months of EV initiation, and the non-EPD group (<jats:italic>n<\/jats:italic>\u2009=\u200987). The clinical parameters and oncological outcomes were compared between groups. The emergence of new metastatic lesions was defined as the detection of metastases in organs not previously identified as metastatic sites at baseline, during prior chemotherapy or immune checkpoint inhibitors (ICIs) before the initiation of EV.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The median overall survival was significantly shorter in the EPD group than in the non-EPD group (6.5 vs. 19.9\u00a0months, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The EPD group had a significantly higher incidence of new metastatic lesions and a lower prevalence of normal Hb levels. Multivariate analysis identified low Hb and the presence of new metastatic lesions as independent predictors of EPD. Among patients with new metastases in the EPD group, an average of 74% of lesions emerged during ICI treatment and 75% involved multiple foci. Notably, more than 50% of these new lesions showed progression at the same sites following EV therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Patients with low hemoglobin levels and new metastatic lesions before EV treatment may be at increased risk for EPD. For these patients, alternative treatment strategies should be considered before initiating EV.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10147-025-02822-1","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T10:39:12Z","timestamp":1751884752000},"page":"1841-1848","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Factors associated with primary resistance to enfortumab vedotin in previously treated patients with metastatic urothelial carcinoma: a multicenter retrospective study"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-2848","authenticated-orcid":false,"given":"Daiki","family":"Ikarashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Sakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Endo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Shirotake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Obara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"2822_CR1","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1111\/iju.13376","volume":"24","author":"J Miyazaki","year":"2017","unstructured":"Miyazaki J, Nishiyama H (2017) Epidemiology of urothelial carcinoma. 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Hayakawa has received institutional research funding from MSD, Chugai Pharma, Astellas Pharma, Astra Zeneca, and Janssen Pharma; Y. Endo has received honoraria for Astellas Pharma, Merck BioPharma, Nippon Kayaku, Bristol Myers Squibb, Ono Pharma, and MSD; S. Shirotake has received honoraria for Ono Pharma, and Bristol Myers Squibb; E. Kikuchi has participated in consulting or advisory roles for Astellas Pharma, Astra Zeneca, Ferring Pharma, Merck BioPharma, Janssen Pharma, Chugai Pharma, and MSD and has participated in speakers bureaus for Astellas Pharma, Astra Zeneca, Merck BioPharma, Janssen Pharma, MSD, Bristol Myers Squibb, Chugai Pharma, and Nippon Kayaku, and has received institutional research funding from MSD, Chugai Pharma, Astellas Pharma, Astra Zeneca, and Janssen Pharma; W. Obara has received honoraria for Astellas Pharma, Takeda Pharma, Ono Pharma, Bristol Myers Squibb, Astra Zeneca, and MSD, and has received institutional research funding from Astellas Pharma, Chugai Pharma, and Janssen Pharma. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved through a centralized ethical review conducted by the Institutional Review Board of the St. Marianna University [Approval No. 6261 (B46)]. This centralized approval was subsequently approved by the institutional review board of Iwate Medical University (Approval No. C-IRB2023-045) and all other participating sites.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Approval of the Research Protocol by the Institutional Review Board"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal studies"}},{"value":"Informed consent was obtained from participants or from the families of deceased patients using the opt-out method through publicly accessible websites.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Registry and registration number of the study\/trial"}}]}}