Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.
Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.
Gynecol Oncol. 2019 Nov;155(2):374-383. doi: 10.1016/j.ygyno.2019.08.019. Epub 2019 Aug 29.
After The Cancer Genome Atlas (TCGA) findings, four novel prognostic groups may direct the management of endometrial cancer (EC): POLE-mutated/ultramutated (POLEmt), microsatellite-instable/hypermutated (MSI), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-mutated (p53mt). However, data about prognosis in each group are different across the studies, and definitive pooled estimates are lacking after validation series. Such data may be crucial in directing clinical study design and establishing the optimal tailored management of patients.
To provide pooled estimates of hazard ratio (HR) for overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) in each prognostic group.
A systematic review and meta-analysis was performed by searching 7 electronic databases, from their inception to April 2019, for studies assessing prognosis in each TCGA EC group. Both univariable and multivariable HR analysis was performed for OS, DSS and PFS in each group, using p53wt as reference group.
Six studies with 2818 patients were included. Regarding OS, pooled HRs were 3.179 and 1.986 for p53mt group, 1.522 and 1.192 for MSI group, and 0.589 and 0.795 for POLEmt group at univariable and multivariable analyses, respectively. Regarding DSS, pooled HR were 5.052 and 2.133 for p53mt group, 1.965 and 1.068 for MSI group, and 0.552 and 0.325 for POLEmt group at univariable and multivariable analyses, respectively. Regarding PFS, pooled HR were 3.512 and 1.833 for p53mt group, 1.354 and 0.817 for MSI group, and 0.287 and 0.217 for POLEmt group at univariable and multivariable analyses, respectively.
Prognosis of p53mt group is consistently the worst one and is further worsened by unfavorable clinicopathological factors. Prognosis of MSI group overlaps with p53wt group but is worsened by unfavorable clinicopathological factors. Prognosis of POLEmt group is the best one and does not seem to be significantly affected by clinicopathological factors.
在癌症基因组图谱(TCGA)研究之后,四个新的预后组可能指导子宫内膜癌(EC)的管理:POLE 突变/超突变(POLEmt)、微卫星不稳定/高度突变(MSI)、拷贝数低/p53 野生型(p53wt)和拷贝数高/p53 突变(p53mt)。然而,不同研究中各组的预后数据存在差异,并且缺乏经过验证系列后的明确汇总估计值。这些数据对于指导临床研究设计和确定患者最佳定制管理可能至关重要。
提供每个预后组中总生存(OS)、疾病特异性生存(DSS)和无进展生存(PFS)的危险比(HR)的汇总估计值。
通过搜索 7 个电子数据库,从其成立到 2019 年 4 月,对评估 TCGA EC 组中每个预后组预后的研究进行了系统评价和荟萃分析。使用 p53wt 作为参考组,对每个组中的 OS、DSS 和 PFS 进行单变量和多变量 HR 分析。
纳入了 6 项包含 2818 名患者的研究。关于 OS,p53mt 组的汇总 HR 分别为 3.179 和 1.986,MSI 组为 1.522 和 1.192,POLEmt 组为 0.589 和 0.795,在单变量和多变量分析中。关于 DSS,p53mt 组的汇总 HR 分别为 5.052 和 2.133,MSI 组为 1.965 和 1.068,POLEmt 组为 0.552 和 0.325,在单变量和多变量分析中。关于 PFS,p53mt 组的汇总 HR 分别为 3.512 和 1.833,MSI 组为 1.354 和 0.817,POLEmt 组为 0.287 和 0.217,在单变量和多变量分析中。
p53mt 组的预后一直最差,并且不利的临床病理因素进一步恶化。MSI 组的预后与 p53wt 组重叠,但不利的临床病理因素会使其恶化。POLEmt 组的预后最好,并且似乎不受临床病理因素的显著影响。