Clinical features of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma: a multi-center real-world retrospective study
10.3760/cma.j.cn112330-20230717-00006
- VernacularTitle:遗传性平滑肌瘤病和肾细胞癌综合征相关性肾癌的临床特征分析：一项全国多中心回顾性研究
- Author:
Yunze XU
1
;
Wen KONG
;
Ming CAO
;
Guangxi SUN
;
Jinge ZHAO
;
Songyang LIU
;
Zhiling ZHANG
;
Liru HE
;
Xiaoqun YANG
;
Haizhou ZHANG
;
Lieyu XU
;
Yanfei YU
;
Hang WANG
;
Honggang QI
;
Tianyuan XU
;
Bo YANG
;
Yichu YUAN
;
Dongning CHEN
;
Dengqiang LIN
;
Fangjian ZHOU
;
Qiang WEI
;
Wei XUE
;
Xin MA
;
Pei DONG
;
Hao ZENG
;
Jin ZHANG
Author Information
1. 上海交通大学医学院附属仁济医院泌尿科，上海 200125
- Keywords:
Carcinoma, renal cell;
Hereditary leiomyomatosis and renal cell carcinoma syndrome;
Fumarate hydratase-deficient;
Genetic testing;
Clinical features;
Thera
- From:
Chinese Journal of Urology
2024;45(3):161-167
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.
