Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma

• Published in: Clinical genitourinary cancer Vol. 22; no. 6; p. 102236
• Main Authors: Hara, Takuto, Teishima, Jun, Okamura, Yasuyoshi, Suzuki, Kotaro, Bando, Yukari, Terakawa, Tomoaki, Chiba, Koji, Hyodo, Yoji, Nakano, Yuzo, Miyake, Hideaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.10.2024
• Subjects: Advanced urothelial carcinoma; Heterogeneity; Immune checkpoint inhibitors; Pembrolizumab; Progession patterns; Advanced urothelial carcinoma; PS; RECIST; Progession patterns; OS; ICIs; Immune checkpoint inhibitors; UC; Heterogeneity; Pembrolizumab; PD; NLR; Hb; PFS
• ISSN: 1558-7673; 1938-0682; 1938-0682
• DOI: 10.1016/j.clgc.2024.102236

This retrospective study evaluates the impact of new lesions on the prognosis of patients with urothelial carcinoma treated with pembrolizumab. Findings indicate that early appearance of new lesions during treatment is associated with significantly poorer overall survival. These results underscore the need for earlier imaging and prompt salvage therapy to improve outcomes in this high-risk patient population. This study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes. This retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes. In this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan–Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001). This study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.