Huang Jiwei, Cai Xingyun, Ng Cheoklong, Luo Yuansheng, Chen Qiong, Wang Zaoyu, Qiao Keying, Kong Wen, Zhang Jin, Chen Yonghui, Zhang Wei, Zhang Jiyang, Zhang Dadong, Wu Guangyu, Chen Haige, Xue Wei
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Urol. 2025 Jun;213(6):739-752. doi: 10.1097/JU.0000000000004475. Epub 2025 Feb 25.
We investigated the efficacy and safety of tislelizumab as neoadjuvant therapy in patients with cisplatin-ineligible high-risk upper tract urothelial carcinoma (UTUC).
In this single-arm phase 2 trial (NCT04672330), 20 patients with high-risk UTUC were enrolled. Eligibility criteria included high-risk UTUC (defined as high-grade UTUC confirmed by endoscopic biopsy or urinary cytology, radiographic evidence of invasion [cT2-T4N0-2M0], and/or hydronephrosis), an Eastern Cooperative Oncology Group performance status of 0 to 2, no previous systemic therapy, and cisplatin ineligibility. Patients received neoadjuvant tislelizumab before radical surgery. Contrast-enhanced MRI was performed before the third dose and again before surgery. The primary end point was pathological complete response rate (ypT0N0). Secondary end points included pathological response rate (≤ypT1N0), objective response rate, disease-free survival, safety profile, and perioperative complications. Multiplex immunofluorescence assessed immune cell populations in the tumor microenvironment.
Among the 20 patients, 13 underwent radical nephroureterectomy, 1 received endoscopic ablation, and 3 had segmental ureteral resection. Three patients declined surgery because of disease progression or adverse events. The pathological complete response rate was 20%, with 45% of patients restaged to ≤ pT1. Median disease-free survival and overall survival were not reached. Grade 3/4 treatment-related adverse event occurred in 15% of patients. MRI analysis revealed higher apparent diffusion coefficient entropy in patients with partial response. Exploratory analysis showed increased PD-L1CD68 macrophages and PD-1CD8 T cells in the tumor stroma of partial and complete responders.
Neoadjuvant tislelizumab showed promising efficacy and manageable toxicity in patients with high-risk, cisplatin-ineligible UTUC. Increased apparent diffusion coefficient entropy on MRI and the presence of PD-L1CD68 macrophages in the tumor stroma may serve as potential predictors of response to neoadjuvant tislelizumab.
TRIAL REGISTRATION NO.: NCT04672330.
我们研究了替雷利珠单抗作为新辅助治疗对不符合顺铂治疗条件的高危上尿路尿路上皮癌（UTUC）患者的疗效和安全性。
在这项单臂2期试验（NCT04672330）中，纳入了20例高危UTUC患者。入选标准包括高危UTUC（定义为经内镜活检或尿细胞学检查确诊的高级别UTUC、侵袭的影像学证据[cT2-T4N0-2M0]和/或肾积水）、东部肿瘤协作组体能状态为0至2、既往未接受过全身治疗以及不符合顺铂治疗条件。患者在根治性手术前接受新辅助替雷利珠单抗治疗。在第三次给药前和手术前再次进行对比增强MRI检查。主要终点是病理完全缓解率（ypT0N0）。次要终点包括病理缓解率（≤ypT1N0）、客观缓解率、无病生存期、安全性概况和围手术期并发症。多重免疫荧光评估肿瘤微环境中的免疫细胞群体。
20例患者中，13例行根治性肾输尿管切除术，1例接受内镜消融，3例行节段性输尿管切除术。3例患者因疾病进展或不良事件拒绝手术。病理完全缓解率为20%，45%的患者分期降至≤pT1。未达到无病生存期和总生存期的中位数。15%的患者发生3/4级治疗相关不良事件。MRI分析显示部分缓解患者的表观扩散系数熵较高。探索性分析显示，部分缓解和完全缓解患者的肿瘤基质中PD-L1⁺CD68巨噬细胞和PD-1⁺CD8 T细胞增加。
新辅助替雷利珠单抗在不符合顺铂治疗条件的高危UTUC患者中显示出有前景的疗效和可管理的毒性。MRI上表观扩散系数熵增加以及肿瘤基质中存在PD-L1⁺CD68巨噬细胞可能作为新辅助替雷利珠单抗反应的潜在预测指标。
NCT04672330。
