{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:37Z","timestamp":1792451797880,"version":"4.5.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"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":[[2026,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify pretreatment factors associated with developing primary resistance to nivolumab plus ipilimumab therapy in patients with advanced renal cell carcinoma (RCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed the clinical characteristics, laboratory data, and tumor-related factors in patients with advanced RCC who initiated nivolumab plus ipilimumab as first-line therapy between January 2018 and July 2021. Primary resistance was defined as radiographic or clinical progression within 3\u00a0months of treatment initiation. Cases with suspected pseudoprogression were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-nine patients met the inclusion criteria; 23 exhibited primary resistance. Univariate analysis identified the following significant predictive factors: body mass index (P\u00a0=\u00a0.006), lymph node metastasis (P\u00a0=\u00a0.021), sarcomatoid differentiation (P\u00a0=\u00a0.035), solitary metastatic organ (P\u00a0=\u00a0.051), liver metastasis (P\u00a0=\u00a0.056), and serum lactate dehydrogenase (LDH) (P\u00a0=\u00a0.094). Receiver operating characteristic curve analysis determined an LDH cutoff value of 174\u00a0U\/L, which was significantly associated with primary resistance (P\u00a0=\u00a0.029). Considering the number of primary resistance cases, multivariable analysis incorporated three candidate variables (lymph node metastasis, sarcomatoid differentiation, and LDH\u00a0\u2265\u00a0174\u00a0U\/L) and identified sarcomatoid differentiation (odds ratio, 4.264; 95% confidence interval (CI), 1.299\u201314.825; P\u00a0=\u00a0.017) and LDH\u00a0\u2265\u00a0174\u00a0U\/L (odds ratio, 3.634; 95% CI, 1.143\u201313.770; P\u00a0=\u00a0.028) as independent predictors of primary resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sarcomatoid differentiation on pretreatment biopsy or elevated serum LDH before treatment initiation may predict primary resistance to nivolumab plus ipilimumab therapy in patients with advanced RCC. Alternative regimens should be considered in such cases, particularly for patients who are likely to experience rapid disease progression or for whom the occurrence of P-res is not clinically acceptable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyaf197","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:12:10Z","timestamp":1764249130000},"page":"337-344","source":"Crossref","is-referenced-by-count":5,"title":["Pretreatment predictive factors for primary resistance to nivolumab plus ipilimumab in advanced renal cell carcinoma: a multicenter collaborative study"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7841-1104","authenticated-orcid":false,"given":"Kimihiko","family":"Masui","sequence":"first","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hayata","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyoto Medical Center , 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinari","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Urology, Kobe City Medical Center General Hospital , 2-1-1 Minatojima Minamimachi, Chuo-ku, Kobe 650-0047 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Urology, Kurashiki Central Hospital , 1-1-1 Miwa, Kurashiki, Okayama 710-8602 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kanno","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyoto Medical Center , 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Urology, Japanese Red Cross Wakayama Medical Center , 4-20 Komatsubara-dori, Wakayama City 640-8558 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology, Shizuoka General Hospital , 4-27-1 Kitaando, Aoi-ku, Shizuoka 420-8527 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Masui","sequence":"additional","affiliation":[{"name":"Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine , 2-174 Edobashi, Tsu, Mie 514-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Segawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto City Hospital , 1-2 Mibuhigashitakadacho, Nakagyo-ku, Kyoto 604-8845 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sojun","family":"Kanamaru","sequence":"additional","affiliation":[{"name":"Department of Urology, Kobe City Nishi-Kobe Medical Center , 5-7-1 Kobekita, Nishi-ku, Kobe 651-2273 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Urology, Tenri Yorozu Hospital , 200 Mishima-cho, Tenri, Nara 632-0016 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Urology, Osaka Red Cross Hospital , 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Shichiri","sequence":"additional","affiliation":[{"name":"Department of Urology, Japanese Red Cross Otsu Hospital , 1-1-35 Nagara, Otsu, Shiga 520-8511 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishitoya","sequence":"additional","affiliation":[{"name":"Department of Urology, Japanese Red Cross Otsu Hospital , 1-1-35 Nagara, Otsu, Shiga 520-8511 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Sumiyoshi","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kita","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-2816","authenticated-orcid":false,"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyoto University Graduate School of Medicine , Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuro","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Miyazaki , 5200 Kihara, Kiyotake, Miyazaki 889-1692 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