{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:44:28Z","timestamp":1788921868882,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) are effective in some cancer patients; however, they may show no efficacy in others. Predictive biomarkers are crucial for appropriately selecting the patients who receive ICI therapy. This study aimed to clarify the predictors of disease progression in urothelial carcinoma (UC) patients treated with an ICI, pembrolizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the response patterns of 50 UC patients who were treated with pembrolizumab, as well as the association between survival and clinicopathological factors. Clinical factors included age, sex, body mass index, clinical courses, laboratory data, metastases, and adverse events. Pathological factors included special variant, squamous differentiation, programmed cell death ligand\u20101 (PD\u2010L1) expression, CD8\u2010positive lymphocytes density, and <jats:italic>CDKN2A\/p16<\/jats:italic> homozygous deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During pembrolizumab treatment, four (8%), 11 (22%), and eight (16%) patients achieved the best\u2010case scenarios of complete response, partial response, and stable disease, respectively. Twenty\u2010seven patients (54%) showed progressive disease. In this study, younger age, lower preoperative neutrophil\u2010to\u2010lymphocyte ratio (NLR), and positive PD\u2010L1 expression were significantly correlated with longer progression\u2010free survival and overall survival. Moreover, lower NLR and positive PD\u2010L1 expression were independently associated with longer OS in multivariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on our observations, lower NLR and positive PD\u2010L1 expression may be independent favorable prognostic markers in UC patients treated with pembrolizumab. These results suggest that both host and tumor status can reflect the effectiveness of pembrolizumab among patients with UC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4779","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T08:59:43Z","timestamp":1655197183000},"page":"4236-4245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lower neutrophil\u2010to\u2010lymphocyte ratio and positive programmed cell death ligand\u20101 expression are favorable prognostic markers in patients treated with pembrolizumab for urothelial carcinoma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-6961","authenticated-orcid":false,"given":"Yu","family":"Miyama","sequence":"first","affiliation":[{"name":"Department of Pathology Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Uro\u2010Oncology Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshiro","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Department of Uro\u2010Oncology Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Pathology Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz127"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.2411"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33297-X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.6795"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30065-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.5534"},{"key":"e_1_2_10_8_1","unstructured":"National Comprehensive CancerNetwork clinical practice guidelines in oncology: bladder cancer version 3.2021."},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.03.055"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00561-4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30496-X"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106818"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0686-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2021.153364"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000000761"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.02.017"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.08.034"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25501"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2006.038802"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1686"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.02.028"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-019-0873-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2017-0555-OA"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2019.04.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.23796"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.03.081"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10050310"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2020.02.005"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S153290"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2013.03.010"},{"issue":"25","key":"e_1_2_10_33_1","first-page":"2483","article-title":"Avelumab maintenance for urothelial carcinoma","volume":"383","author":"Powles T","year":"2020","journal-title":"Reply N Engl J Med"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgo.2021.07.002"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58351-6"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4779","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4779","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T05:53:08Z","timestamp":1692683588000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":34,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/cam4.4779"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4779","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]},"assertion":[{"value":"2021-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}