Risk Factors Of Lymph Node Metastasis In Endometrial Cancer And Its Clinical Application Value

Objective To explore the risk factors of lymph node metastasis and its clinical application value in the patients with endometrial cancer(EC),and to provide references for preoperative and intraoperative evaluation of lymph node metastasis status and formulation of surgical procedures.Methods Preoperative laboratory results and clinicopathological data of 393 EC patients who underwent surgical treatment in the Department of Gynecology,Affiliated Hospital of Qingdao University from January 2014 to February 2019 were retrospectively analyzed.Mann-Whitney U test(continuous variables),?~2 test or Fisher's exact probability method(categorical variables)were used for univariate analysis,and binary Logistic regression analysis was used for multivariate analysis to investigate the risk factors for EC pelvic lymph node metastasis and para-aortic lymph node metastasis.Sensitivity,specificity,positive predictive value and negative predictive value,as well as the correlation between the number of independent risk factors and the rate of lymph node metastasis were used to evaluate the clinical application value of related risk factors.Results1.All the 393 EC patients included in this study underwent total hysterectomy+bilateral adnexectomy+pelvic lymphadenectomy,and 305 of them underwent para-aortic lymphadenectomy at the same time.Postoperative pathological results showed that a total of 50 patients had lymph node metastasis,including 30 cases with pelvic lymph node metastasis alone,5 cases with para-aortic lymph node metastasis alone,and 15 cases with both of them.The total rate of lymph node metastasis was 12.7%(50/393),the rate of pelvic lymph node metastasis was 11.5%(45/393),and the rate of para-aortic lymph node metastasis was 6.6%(20/305).2.Univariate analysis of pelvic lymph node metastasis showed that preoperative high levels of serum carbohydrate antigen 125(CA125),human epididymis protein 4(HE4),peripheral blood monocyte to lymphocyte ratio(MLR),platelet to lymphocyte ratio(PLR),and low level of lymphocyte count(LY),as well as non-endometrioid type histopathology,poorly differentiated tumor,tumor size?3cm,myometrial invasion?1/2,para-uterine or vaginal involvement,adnexal involvement,positive peritoneal cytology,and lymphovascular space invasion(LVSI)were associated with pelvic lymph node metastasis(P<0.05).EC patients without lymph node metastasis were selected as the control group,while those with pelvic lymph node metastasis as the comparison group.According to ROC curve,the cut-off value of meaningful laboratory indicators by the univariate analysis for judging pelvic lymph node metastasis in EC patients were as follows:CA125 was 27.6U/mL,HE4 was 132pmol/L,LY was 1.67×10~9/L,MLR was0.19,and PLR was 166.Multivariate analysis revealed that serum CA125?27.6U/mL(OR=6.10,95%CI:2.31-16.07,P=0.000),HE4?132pmol/L(OR=4.25,95%CI:1.65-10.94,P=0.003),non-endometrioid type histopathology(OR=16.64,95%CI:5.96-46.47,P=0.000),myometrial invasion?1/2(OR=5.30,95%CI:2.07-13.55,P=0.001),positive peritoneal cytology(OR=4.70,95%CI:1.21-18.27,P=0.025),and LVSI(OR=3.11,95%CI:1.09-8.92,P=0.034)were independent risk factors for pelvic lymph node metastasis.The area under the ROC curve(0.779),sensitivity(77.8%)and negative predictive value(96.1%)of CA125 for pelvic lymph node metastasis were the highest;the specificity(86.0%)and positive predictive value(30.4%)of HE4 were the highest;and the negative predictive values of HE4,LY,MLR and PLR were all above90%.When none of the six independent risk factors were present,the rate of pelvic lymph node metastasis was 0.0%(0/154).With the increase of the number of independent risk factors,the rate of pelvic lymph node metastasis was increased significantly.When any five or more independent risk factors were present,the rate of pelvic lymph node metastasis was 100.0%(9/9).3.Univariate analysis of para-aortic lymph node metastasis showed that preoperative high levels of CA125 and HE4,non-endometrioid type histopathology,poorly differentiated tumor,tumor size?3cm,myometrial invasion?1/2,para-uterine or vaginal involvement,adnexal involvement,positive peritoneal cytology,LVSI and pelvic lymph node metastasis were associated with para-aortic lymph node metastasis(P<0.05).According to ROC curve,the cut-off values of CA125 and HE4 for para-aortic lymph node metastasis were 55.5U/mL and 105pmol/L,respectively.Multivariate analysis showed that non-endometrioid type histopathology(OR=10.24,95%CI:3.02-34.71,P=0.000)and pelvic lymph node metastasis(OR=21.84,95%CI:6.49-73.48,P=0.000)were independent risk factors for para-aortic lymph node metastasis.The area under the ROC curve(0.776),sensitivity(60.0%),specificity(86.7%),positive predictive value(24.0%)and negative predictive value(96.9%)of para-aortic lymph node metastasis judged by CA125 were all higher than HE4.When the two independent risk factors were not present,either one or both of them existed,the rates of para-aortic lymph node metastasis were 0.4%,13.8%?26.7%and 61.1%,respectively.Conclusions1.This study indicate that preoperative increased serum CA125 and HE4 levels,non-endometrioid type histopathology,deep myometrial invasion,positive peritoneal cytology,and LVSI are independent risk factors for pelvic lymph node metastasis in patients with EC.Non-endometrioid type histopathology and pelvic lymph node metastasis are independent risk factors for para-aortic lymph node metastasis.2.In the evaluation of pelvic lymph node metastasis in EC patients,the sensitivity of CA125 is the highest,the specificity and positive predictive value of HE4 are the highest,and the negative predictive value of CA125,HE4,LY,MLR and PLR are all over 90%.The sensitivity,specificity,positive predictive value and negative predictive value of CA125 are all higher than HE4 in the evaluation of para-aortic lymph node metastasis.3.The presence or absence and number of independent risk factors can reflect the metastasis rate of pelvic lymph nodes and para-aortic lymph nodes of EC,patients without independent risk factors almost have no lymph node metastasis.4.Preoperative and intraoperative evaluation of the status of lymph node metastasis is helpful to perform selective lymphadenectomy in EC patients,and to guide postoperative adjuvant therapy and prognosis.