A considerable proportion of premenopausal women are diagnosed with endometrioid endometrial carcinoma, the majority of who are classified as preoperative clinical stage I . Younger premenopausal patients with clinical I stage endometrioid endometrial cancer have a more favorable prognosis than postmenopausal patients. An earlier large-scale study reported a 5-year disease-specific survival rate of 93% in women younger than 40 years . The higher survival of younger patients may be partly attributed to early-stage and low-grade tumors.
For patients with clinical stage I endometrioid endometrial carcinoma, the traditional surgical approach is total hysterectomy and BSO with or without pelvic and/or para-aortic lymph node dissection according to the existence of high-risk factors. Young premenopausal women with clinical stage I endometrioid endometrial carcinoma subjected to total hysterectomy and BSO often not only suffer from permanent loss of fertility but also experience climacteric symptoms of decreased estrogen production. Hence, ovarian preservation is a feasible option for this group of patients in the absence of high risk factors. Wright and co-workers confirmed the safety and feasibility of ovarian preservation in a population-based analysis . Consistently, Lee et al. [7, 13] reported that ovarian preservation in premenopausal women with early-stage endometrial carcinoma was not associated with poorer outcomes. Another study by Richter and colleagues showed that BSO not only induced better disease-free survival but also did not affect overall survival in young endometrial carcinoma patients . Jia and Zhang recently performed a meta-analysis of comparing overall survive between BSO group (9376 cases) and ovary preservation group (1340 cases) in 10716 patients from four studies from the USA, Korea, and China. They demonstrated that ovary preservation can significantly improve the overall survive and did not adversely impact the reduced recurrence-free survival in pre-menopausal patients with early-stage endometrial cancer. Although the patients with ovary preservation had a 2.1 folds risk of recurrence, they obtained a higher overall survive probability in the long run .
However, occasionally these patients present with occult ovarian malignant involvement, as evident from postoperative detailed pathological inspection. In our analysis, ovarian malignant involvement occurred in 4.5% patients with clinical stage I endometrioid endometrial carcinoma, in keeping with Lin et al.  who reported ovarian involvement in 5% of their patient group. The ratio of ovarian malignant involvement in low risk patients was 1.04% while patients in the sub-high risk group positive for at least one risk factor showed higher ovarian involvement (6.6%). Data from Kaplan-Meier analysis in the current study showed longer disease-free and higher overall survival rates in patients without ovarian malignant involvement relative to those with ovarian involvement. Ovarian malignant involvement, representing an advanced stage of disease, is generally associated with poorer prognosis. Effective ways to identify patients at higher risk of ovarian malignant involvement and preoperative risk factors that can be used to predict ovarian malignant involvement, especially to distinguish the subgroups of patients suitable for receiving staging surgery for endometrioid endometrial cancer, remains an urgent requirement. The majority of studies to date have focused on postoperative pathological prediction factors, such as myometrial invasion, tumor size, lymphovascular involvement, tumor grade, lymph node metastasis and cervical invasion. Sun and co-workers reported adnexal morphology, lymph node involvement (confirmed via frozen sections) and tumor spread in the peritoneal cavity as the most significant predictors of ovarian involvement, based on data from 203 young women with early-stage endometrial cancer . Chen et al.  utilized postoperative histological and pathologic data (tumor size, histological type, pathological grade, peritoneal cytology, invasive depth of myometrium, uterine serosal involvement, lymph vascular space invasion, cervical involvement, and adnexa involvement) as effective parameters for distinguishing synchronous primary cancers of endometrium and ovary and endometrial cancer with metastasis to the adnexa. Clinicopathological characteristics (i.e., tumor size, myometrial invasion, lymphovascular space involvement, lymph node metastasis, tumor grade, cervical invasion and ovarian enlargement ≥5 cm) were used to assess the likelihood of ovarian malignancy by Yoshino and colleagues, who showed the presence of ovarian metastasis in 4.5% patients and identified lymph node metastasis and deep myometrial invasion as significant predictive factors for ovarian metastasis and lymph node metastasis, respectively . Li et al.  highlighted specific post-operation parameters, such as deep myometrial invasion, positive lymph node metastasis, positive LVSI, and high histologic grade (G2-G3), associated with ovarian involvement in younger endometrial cancer patients. Furthermore, in multivariate analysis, only deep myometrial invasion was an independent risk factor for ovarian involvement. However, the information is meaningless, because all the above risk factors were evaluated following the operation and not useful for gynecologists prior to surgery. Here, we focused on identifying potential preoperative predictive factors of ovarian malignant involvement, with the aim of providing beneficial guidelines for the appropriate surgical interventions.
Our results suggested that preoperative imaging of myometrial invasion depth, the gross appearance of the ovaries, and preoperative serum CA125 level, were predictive risk factors of ovarian malignant involvement in premenopausal clinical stage I endometrioid endometrial carcinoma patients, which could aid in preoperative counseling of patients and clinical decision-making for the first time. Univariate and multivariate logistic analyses further validated preoperative imaging of myometrial invasion depth, the gross appearance of the ovaries, and preoperative serum CA125 as independent risk predictors of ovarian involvement in our patient group. Consistently, AUC data showed that combination of preoperative myometrial invasion depth, the gross appearance of the ovaries, and preoperative serum CA125 level had strong predictive value for postoperative ovarian malignant involvement to a degree. Preoperative deep myometrial invasion depth and serum CA125 level have been previously identified as prognostic factors in ovarian metastasis . Yu et al. found the preoperative imaging of myometrial invasion depth by magnetic resonance imaging had the values for diagnostic sensitivity (69.2%), specificity (80%), positive predictive value (50%), and negative predictive value (90%), with postoperative pathologic assessment used as the reference standard in a total of 58 endometrial carcinoma cases research . Our study results are in accordance with them, with lower sensitivity (52.94%) and higher specificity (97.27%). Even though, the preoperative imaging of myometrial invasion depth still has medium preoperative predictive value for postoperative ovarian malignant involvement due to its higher specificity. Furhtermore, Jiang and colleagues reported that preoperative serum CA125 is an effective predictor of lymph node metastasis in patients with endometrial cancer, in particular, clinical stage I . Analysis of the combined factors also revealed utility as a predictive marker of ovarian malignant involvement to some extent. CA125 has been applied as a tumor marker of ovarian carcinoma since its discovery 30 years ago . A large proportion (80%) of women with primary epithelial ovarian carcinoma and secondary ovarian tumor (70%) are diagnosed based on elevated CA125 levels [24, 25]. Taken together, our data suggest that the combination of preoperative myometrial invasion depth, the gross appearance of the ovaries and preoperative serum CA125 level may present an effective predictive risk factor of postoperative ovarian malignant involvement in patients with clinical stage I endometrioid endometrial carcinoma.
Our study had several of limitations that should be acknowledged. One significant factor was the origin of ovarian tumor. Although we set stricter clinicopathological criteria for diagnosis, classification of a part of patients into ovarian malignant involvement or simultaneous uterine and ovarian carcinoma groups was difficult. Moreover, precursor lesions, such as endometrial hyperplasia or concurrent ovarian endometriosis, were not consistently addressed in pathology reports, potentially affecting the final diagnosis. Therefore, novel powerful genetic tools require development for accurate classification of patients displaying complex symptoms in forthcoming research, which would lead to a more accurate research database. Second, large-scale prospective clinical studies are necessary to ascertain whether the benefits of ovarian preservation outweigh the risks of surgical procedures in clinical stage I endometrioid endometrial carcinoma to reduce bias.