RT Journal Article SR Electronic T1 Efficacy of Pembrolizumab as Second or Third-line Therapy for Local Advanced and Metastatic Urothelial Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2563 OP 2573 DO 10.21873/anticanres.17628 VO 45 IS 6 A1 MATSUO, TOMOHIRO A1 MIYATA, YASUYOSHI A1 HARADA, JUNKI A1 ITOH, ITSUHO A1 MATSUDA, TSUYOSHI A1 ASAI, AKIHIRO A1 KONDO, TSUBASA A1 KURATA, HIROKI A1 SAKAI, SUZUNA A1 ITOH, HIDENORI A1 MITSUNARI, KENSUKE A1 IMAMURA, RYOICHI YR 2025 UL http://ar.iiarjournals.org/content/45/6/2563.abstract AB Background/Aim: Pembrolizumab is widely used as second-line (2L) chemotherapy for unresectable advanced urothelial carcinoma (UC). While its anticancer effects are known, survival data, particularly on metastatic status, remain limited. Studies on pembrolizumab efficacy, including survival analyses in third- or later-line (≥3L) settings, are also scarce. This study analyzes pembrolizumab efficacy in locally advanced or metastatic UC in ≥2L settings to provide insights for optimizing treatment sequencing and patient management.Patients and Methods: This retrospective study evaluated the cytoreductive effects and survival outcomes of pembrolizumab as 2L or ≥3L treatment in 113 UC patients. Objective response rates (ORRs) were calculated for all patients and separately for 2L and ≥3L treatment groups.Results: The ORRs were 23.0%, 21.8%, and 26.9% for the entire cohort, 2L treatment group, and ≥3L treatment group, respectively, with no significant intergroup differences. The median OS of total patients was 12.2 months, with no significant difference between the 2L and 3L treatment groups (p=0.120). The OS was significantly shorter in patients with liver metastasis than in those without (p=0.004), whereas no significant OS differences were found among patients with lymph node, bone, and lung metastases. Patients with lymph node-only or single-site metastasis had significantly longer OS than did those with distant-organ or multiple-site metastases.Conclusion: Pembrolizumab offered similar efficacy as 2L and ≥3L therapy in advanced UC, supporting use beyond second-line settings. In addition, metastasis, specifically distant metastasis and liver involvement, predicted poorer OS of advanced UC patients under pembrolizumab. These findings support more informed patient selection and treatment sequencing in real-world care.