Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Clin Genitourin Cancer. 2024 Dec;22(6):102236. doi: 10.1016/j.clgc.2024.102236. Epub 2024 Oct 9.
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.
本研究调查了接受 pembrolizumab 治疗的尿路上皮癌患者的反应模式变化，包括靶病灶增大和新病灶出现，并评估了新病灶对患者结局的影响。
本回顾性分析纳入了铂类治疗失败后接受 pembrolizumab 治疗的尿路上皮癌患者。采用实体瘤反应评价标准评估靶病灶大小和新病灶的出现。患者分为 2 组：起始治疗后 28 至 84 天内进展的患者为原发性进展性疾病（PD）组，起始治疗后 84 天以上进展的患者为继发性 PD 组。生存分析评估新病灶对患者结局的影响。
本研究中，42 例患者发生原发性 PD，37 例患者发生继发性 PD。在原发性 PD 患者中，分别有 64.3%、73.8%、45.2%的患者靶病灶大小增加 20%或以上、出现新病灶、以及靶病灶大小增加和出现新病灶。Kaplan-Meier 分析显示，原发性 PD 且有新病灶的患者在 PD 后总生存显著短于仅有靶病灶增长的患者和继发性 PD 患者（均 P <.001）。
本研究揭示了尿路上皮癌患者接受 pembrolizumab 治疗时原发性 pembrolizumab 耐药和新病灶出现的反应模式异质性，以及治疗早期即出现新病灶。应更早进行影像学评估以评估新病灶的出现，从而进行序贯治疗。
