| BackgroundEndometrial cancer(EC)is one of the most common gynecological malignancies,occurs more common in middle-aged and elderly women,and shows a trend of younger in recent years.Although the overall prognosis is relatively good,the prognosis for patients with recurrence is unfavorable.According to guidelines,risk factors affecting the prognosis of EC include age,myometrial invasion,lymph-vascular space invasion(LVSI),and histopathologic grade(G).The more risk factors there are,the higher the risk of recurrence.However,the impact of LVSI on the prognosis of EC remains controversial,and lacks support from large sample size studies.We conducted a multicenter retrospective cohort study in China to evaluate the prognostic value of LVSI for EC patients,and find risk factors of disease-free survival(DFS)and overall survival(OS).MethodsWe retrospectively analyzed the clinical data of EC patients who underwent surgical treatment from 2010 to 2019 in seven China medical centers,and patients were divided into LVSI positive and negative group according to the postoperative pathology.A propensity score matching(PSM)algorithm was used to balance characteristics of the two groups,and a after-matching cohort was obtained.In the matched cohort,other characteristics except LVSI were balanced,and the two groups were comparable,so as to explore the influence of LVSI on the prognosis of EC patients.Characteristics between groups were compared by the Chi-square test.Kaplan-Meier survival analysis was used to compare the DFS and OS of the two groups.In addition,subgroups analyses stratified by International Federation of Gynecology and Obstetrics(FIGO)stage and histological types were conducted to further explore the prognostic value of LVSI for different EC patients.Predictive factors of LVSI in EC patients were explored by univariate and multivariate logistic regression(LR)analyses.Finally,univariate and multivariate Cox proportional hazards regression analyses were used to find independent risk factors of DFS and OS.ResultsA total of 3715 EC patients were enrolled,and the positive rate of LVSI was 9.31%(346/3715).The median(interquartile range)duration of follow-up was 39(22-63)months,136(3.7%)patients relapsed and 73(2.0%)patients died.Chi-square test results showed significant difference in carbohydrate antigen-125(CA-125)(p<0.001),surgical route(p=0.041),surgical scope(p<0.001),histological types(p<0.001),myometrial invasion(p<0.001),FIGO stage(p<0.001)and adjuvant therapy(p<0.001)between the two groups.After matching,the difference between groups was well balanced.In the original cohort,there were statistical differences of both DFS(p<0.001)and OS(p=0.005)between LVSI present and absent groups.After matching,there was statistical difference of DFS(p<0.001),but not OS(p=0.072)between groups.Results of subgroups analyses in after matching cohorts were as follows:① There was no significant difference in DFS(p=0.316)and OS(p=0.469)between LVSI present and absent groups in FIGO stage Ⅰ-Ⅱ patients;②There were statistical differences in both DFS(p=0.004)and OS(p=0.018)between the two groups in FIGO stage Ⅲ-Ⅳ patients;③In patients with endometrioid EC,there was significant differences in DFS(p=0.005),but not OS(p=0.656);④In non-endometrioid EC patients,there were no statistically significant differences in neither DFS(p=0.536)nor OS(p=0.512)between the two groups.Independent predictive factors of LVSI in EC patients:G3[Odd ratio(OR)=2.199,95%confidence interval(CI):1.690-2.860,p<0.001],myometrial invasion(depth<1/2:OR=7.096,95%CI:2.243-22.444,p=0.001:depth≥1/2:OR=20.12,95%CI:6.300-64.289,p<0.001),FIGO stage Ⅱ(OR=1.868,95%CI:1.246-2.801,p=0.002),FIGO stage Ⅲ(OR=5.843,95%CI:4.339-7.867,p<0.001)and FIGO stege Ⅳ(OR=7.303,95%CI:3.810-13.996,p<0.001).In multivariate Cox proportional hazards regression analysis,LVSI[Hazard ratio(HR)=2.085,95%CI:1.229-3.537,p=0.006],age≥60(HR=3.277,95%CI:1.950-5.508,p<0.001),G3(HR=3.008,95%CI:1.753-5.162,p<0.001),FIGO stage Ⅲ(HR=3.678,95%CI:2.026-6.678,p<0.001)and FIGO stage Ⅳ(HR=2.804,95%CI:1.027-7.651,p=0.044)were independent risk factors for DFS.Age≥60(HR=5.651,95%CI:2.647-12.064,p<0.001),FIGO stage Ⅲ(HR=5.935,95%CI:2.314-15.222,p<0.001),FIGO stage Ⅳ(HR=8.197,95%CI:2.289-29.353,p=0.001)and non-endometrioid tumors(HR=2.678,95%CI:1.275-5.627,p=0.009)were independent predictors for OS.Conclusions1.LVSI is a poor prognostic factor for EC patients,especially for patients with endometrioid and advanced tumors.G3,myometrial invasion and FIGO stage Ⅱ-Ⅳ are closely related to the occurrence of LVSI.2.LVSI,age,non-endometrioid tumors,G3 and advanced tumors are independent risk factors for poor prognosis of EC patients. |
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