Br J Cancer:浆细胞样尿路上皮癌的系统疗法反应及基因表达状况

2021-01-27 xiaozeng MedSci原创

浆细胞样尿路上皮癌(PUC)是尿路上皮癌(UC)的一种罕见的组织学亚型。其具有弥漫性的生长模式,且在诊断时比传统的UC更容易发生疾病的局部发展。

浆细胞样尿路上皮癌(PUC)是尿路上皮癌(UC)的一种罕见的组织学亚型。其具有弥漫性的生长模式,且在诊断时比传统的UC更容易发生疾病的局部发展。既往研究显示,在80%的PUC病例中均出现编码E-钙粘着蛋白的CDH1基因的截短突变。而在其他PUC病例中也发现了CDH1启动子区域的高甲基化。

术前以顺铂为基础的化疗策略可提高患者的病理反应和癌症特异性生存率,是现代UC治疗的不可或缺的组成部分。组织学亚型的存在并不损害鳞状或腺样分化的UC患者的术前化疗的疗效。然而,目前对于PUC患者的术前化疗的实用性仍知之甚少。


该研究旨在探究非转移性PUC术前铂类化疗的疗效以及晚期PUC的免疫检查点抑制剂(ICIs)的疗效。

研究人群和主要临床分析亚组的关系图

研究人员前期收集了使用ICI治疗的非转移性PUC和晚期PUC病例数据。并将相关结果与未另作说明的已发表的尿路上皮癌患者队列进行比较。


研究人员共收集了81例非转移性PUC患者信息。在接受新辅助化疗的局限性疾病患者中,患者的病理完全缓解和降期率分别为12%和21%。患者病理分期的降低与临床结果的明显改善无关。

浆细胞样尿路上皮癌患者的无复发生存率和总生存率降低

研究人员发现,在手术时高达18%的局部疾病病例和28%的局部晚期病例患有不可切除的疾病。经ICI治疗的晚期PUC(N = 21)患者的无进展生存期和总生存期分别为4.5和10.5个月,缓解率为38%。研究人员分别在3%和15%的病例中观察到FGFR3和DNA损伤反应相关基因突变的发生。


总而言之,以上的研究结果显示,PUC与疾病的高负担和较差的化学敏感性相关。对该疾病亚型认识的提高将有利于新的治疗策略的研发。


原始出处:

Teo, M.Y., Al-Ahmadie, H., Seier, K. et al. Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma. Br J Cancer (21 January 2021).

 

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