Clinical Characterization of Mismatch Repair Gene-Deficient Metastatic Castration-Resistant Prostate Cancer

被引：8

作者：

Ye, Senlin ^{[1
]}

Wang, Haohui ^{[1
]}

He, Kancheng ^{[1
]}

Peng, Mou ^{[1
]}

Wang, Yinhuai ^{[1
]}

Li, Yuanwei ^{[2
]}

Jiang, Shusuan ^{[3
,4
]}

Li, Jin ^{[5
]}

Yi, Lu ^{[1
]}

Cui, Rongrong ^{[6
]}

机构：

[1] Cent South Univ, Dept Urol, Xiangya Hosp 2, Changsha, Peoples R China

[2] Hunan Prov Peoples Hosp, Dept Urol, Changsha, Peoples R China

[3] Hunan Canc Hosp, Dept Urol, Changsha, Peoples R China

[4] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Changsha, Peoples R China

[5] Cent Hosp Xiangtan, Dept Urol, Changsha, Peoples R China

[6] Cent South Univ, Xiangya Hosp 2, Dept Metab & Endocrinol, Changsha, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2020年 / 10卷

关键词：

mismatch repair deficiency; castration-resistant prostate cancer; next-generation sequencing; cell-free DNA; novel hormone therapy; LYNCH SYNDROME; PD-1; BLOCKADE; TUMORS;

D O I：

10.3389/fonc.2020.533282

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mismatch repair-deficient (dMMR) prostate cancer is rare and has not been well studied. We aimed to evaluate the clinical characterization of dMMR metastatic castration-resistant prostate cancer (mCRPC) patients. The MMR genes include MLH1, MLH3, MSH2, MSH6, PMS1, PMS2, and EPCAM, and were analyzed by targeted sequencing of plasma cell-free DNA samples. A total of 109 mCRPC patients were identified, including 50 patients with MMR alterations (pathogenic alterations,n= 7; alterations of unknown significance,n= 43) and 59 patients with wild-type MMR. For the seven patients with pathogenic MMR alterations, the median age at diagnosis was 63.5 years, and 42.9% had a Gleason score >= 8. The median time from androgen deprivation therapy (ADT) initiation to CRPC was 24 months. Compared with the wild-type MMR subgroup, patients with MMR alterations, pathogenic MMR alterations, or MMR alterations of unknown significance showed higher rates of hotspot missense mutations or copy number amplifications in the AR gene (24/50 vs. 10/59,P= 7.8 x 10(-4); 7/7 vs. 10/59,P= 2.5 x 10(-5); 17/43 vs. 10/59,P= 0.013). The presence of any MMR alterations was associated with an inferior response to abiraterone [median progression-free survival (PFS): 5.0 vs. 10.9 months,P= 0.022]. Shorter PFS times were observed in both the pathogenic MMR alteration subgroup (median PFS: 5 months) and the MMR alterations of unknown significance subgroup (median PFS: 5.3 months), compared with the PFS of those with wild-type MMR genes (median PFS: 10.9 months,P= 0.052). There was no statistically significant difference in response to docetaxel chemotherapy between the MMR alterations of unknown significance and the wild-type MMR subgroups (median PFS: 8.2 vs. 8.1 months,P= 0.23). Our results demonstrate that dMMR mCRPC patients have an equivalent response to standard ADT and taxane-based chemotherapy treatments compared with wild-type MMR patients. Patients with both pathogenic and unknown significance alterations of MMR genes had poorer responses to abiraterone therapy.

引用

页数：6

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