Clinicopathological Characteristics And Analysis For Recurrence Risk Of Patients With Coexistence Of Endometrial And Ovarian Carcinoma

BackgroundMultiple primary malignant carcinomas involving the female genital tract are relatively rare,only accounting for 1%to 2%of all gynecologic malignancies.Synchronous primary cancers of the endometrium and ovary(SCEO)are the most common.Studies have revealed that the clinical and pathological characteristics of SCEO are different from endometrial cancer with ovarian metastasis(ECOM).At present,patients with coexistence of endometrial and ovarian carcinomas(CEOC)are usually divided into double primary cancer and metastatic cancers using the classic pathological diagnostic criteria by Scully et al.With the development of next-generation sequencing,several studies have shown that most of the patients diagnosed as SCEO according to the classic diagnostic criteria have clonal correlation between the endometrial and ovarian cancer foci,suggesting that the nature of this type of tumor is not double primary cancer but metastatic cancer.It poses a great challenge to both diagnosis and determination of the prognosis in SCEO patients.ObjectiveTo explore the clinicopathological features and risk factors of postoperative recurrence in patients with CEOC,build a recurrence risk prediction model and evaluate it,so as to provide theoretical support for accurately judging the prognosis of patients with CEOC.MethodsA total of 67 patients with endometrial cancer who were admitted to the Department of Gynecology of Qilu Hospital of Shandong University from January 2008 to December 2020 were included in the study.All these patients received surgeries and postoperative pathologically confirmed endometrial carcinoma with ovarian carcinomas.Firstly,these patients were divided into SCEO group(36 cases)and ECOM group(31 cases)for comparison by the classic pathological diagnosis proposed by Scully et al and the clinical,pathological,and prognostic differences between the two groups were analyzed.Then,the basic variables of patients in the two groups were matched 1:1 by propensity score matching(PSM)method.The matching variable is age,menopausal status,ovarian tumor differentiation,fallopian tube involvement,depth of myometrial invasion,endometrial tumor differentiation,cervical invasion and lymph node involvement,and match tolerance was set as 0.2.After matching,17 patients with SCEO and 31 patients with ECOM were obtained and were analyzed again.We performed univariate and multivariate Cox proportional hazard model to identify independent risk factors of postoperative recurrence,and build a prediction model of recurrence risk.ResultsCompared with patients in ECOM group,patients in SCEO group were younger(median age 50 years old vs 56 years old,P=0.005),and most of them were still menopausal(63.9%vs 35.5%,P=0.020).The majority of patients in SCEO group had no fallopian tube involvement(88.9%vs 48.4%,P<0.001)and only invade the endometrium mucosa or superficial myometrium(77.8%vs 41.9%,P=0.003).High or moderate differentiation of ovarian tumors(77.8%vs 48.4%,P=0.012)and high or moderate differentiation of endometrial tumors(80.6%vs 48.4%,P=0.006)are more common in SCEO group.Cervical invasion(77.8%vs 51.6%,P=0.025)and lymph node metastasis(72.2%vs 32.3%,P=0.001)were rare in the SCEO group.However,there was no significant difference in the progression free survival(PFS)between the SCEO group and the ECOM group before and after PSM(20 months VS 18 months,P=0.282,16 months VS 18 months,P=0.592).Univariate Cox proportional hazard model were used for single factor analysis of clinicopathological indicators.Several factors were significantly associated with postoperative recurrence CEOC patients.These factors included menopausal status(P=0.046),pathological types of ovarian malignancies(P=0.012),the differentiation grade of ovarian carcinoma(P=0.003),fallopian tube involvement(P<0.001),depth of myometrial invasion(P=0.003),pathological types of endometrial malignancies(P<0.001),the differentiation grade of ovarian carcinoma(P=0.001)and lymph node metastasis(P=0.003).Variables with statistical significance in the univariate analysis were investigated by multivariate analysis.Stepwise regression analysis was performed using the step forward method.Inclusion criteria were appropriately relaxed,exposure variables with P-values less than 0.1 were considered for inclusion into the multivariable analysis model.Multivariate analysis results showed that the pathological types of endometrial malignancies(P=0.006),fallopian tube involvement(P=0.008)and depth of myometrial invasion(P=0.019)were independent risk factors influencing recurrence of CEOC patients.A prediction model of recurrence risk of CEOC patients was built according to the results of multivariate Cox regression analyses.The patients can be divided into high-risk and low-risk groups according to their risk score and Kaplan-Meier analysis for PFS revealed significant difference between the groups(P<0.001).Conclusions1.SCEO patients are younger,majority of those patients are premenopausal.Most SCEO patients are not with fallopian tube involvement,the differentiation grade of ovarian carcinomas are higher,endometrial tumors usually only invade the endometrium mucosa or superficial myometrium and are well/moderately differentiated,and cervical invasion and lymph node metastasis occurred rarely.2.It was confirmed by the PSM method that the PFS between SCEO patients and ECOM patients have no significant difference under the same clinicopathological and postoperative combined treatment conditions.The classic pathological diagnostic criteria used to distinguish the two types of patients do not always reflect clinical outcomes.3、The pathological types of endometrial malignancies,fallopian tube involvement and depth of myometrial invasion are independent risk factors influencing recurrence of CEOC patients.4、The risk factor-based recurrence model proposed in this study may outperform traditional pathological classification criteria in predicting PFS in CEOC patients,which can effectively identify and classify patients with high-risk and low-risk of recurrence.It provides valuable help for the clinical management and prognosis judgment of CEOC patients.