Ding Xinjia, Zong Jianguo, Li Xiang, Bai Xiaoyan, Tan Bowen, Sun Weibing, Wang Ruoyu, Ding Yan
Department of Urology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People's Republic of China.
The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People's Republic of China.
Onco Targets Ther. 2021 Mar 25;14:2177-2183. doi: 10.2147/OTT.S297149. eCollection 2021.
Upper tract urothelial carcinoma (UTUC) has a high recurrence rate and is likely refractory to systemic chemotherapy. The long-term outcomes and responses to immunotherapy and retreatment regimen after tumor recurrence for such cases had not yet been well-documented.
Here we report a unique case of long-term follow-up with a 67-year-old woman, who was diagnosed with advanced UTUC, received radical nephroureterectomy with bladder cuff, and was refractory to chemotherapy with cisplatin and gemcitabine. Positive PD-L1 expression and somatic mutation of Ser249Cys in FGFR3 were identified in the tumor tissue. The patient then received pembrolizumab monotherapy and achieved complete response (CR) after 6 cycles of treatment. She discontinued pembrolizumab treatment thereafter but remained in CR for 3 years and 7 months until the recurrence of tumor in the right mid-ureter. The patient was then retreated with a combination of pembrolizumab and erdafitinib, and achieved CR again after the third cycle of treatment.
We reported here a rare case of UTUC with concurrent pathogenic mutations in FGFR3 and TP53 with positive PD-L1 expression. The patient archived exceptional therapeutic responses to PD-1 blockade treatment and retreatment with combination of pembrolizumab and erdafitinib. Our results provide new insight into the duration of immunotherapy and the retreatment strategy after tumor recurrence based on individual genomic profiles.
上尿路尿路上皮癌（UTUC）复发率高，可能对全身化疗耐药。此类病例肿瘤复发后的长期预后以及免疫治疗反应和再治疗方案尚未有充分记录。
在此，我们报告一例对一名67岁女性进行长期随访的独特病例，该患者被诊断为晚期UTUC，接受了根治性肾输尿管切除术及膀胱袖状切除术，对顺铂和吉西他滨化疗耐药。在肿瘤组织中鉴定出PD-L1表达阳性以及FGFR3基因存在Ser249Cys体细胞突变。该患者随后接受帕博利珠单抗单药治疗，6个周期治疗后达到完全缓解（CR）。此后她停止了帕博利珠单抗治疗，但保持CR状态3年7个月，直至右输尿管中段肿瘤复发。该患者随后接受帕博利珠单抗和厄达替尼联合再治疗，第三个周期治疗后再次达到CR。
我们在此报告一例罕见的UTUC病例，其FGFR3和TP53同时存在致病性突变且PD-L1表达阳性。该患者对PD-1阻断治疗以及帕博利珠单抗和厄达替尼联合再治疗取得了出色的治疗反应。我们的结果为基于个体基因组特征的免疫治疗持续时间以及肿瘤复发后的再治疗策略提供了新的见解。
