Endometrial cancer has the highest incidence among gynecological cancers in Western countries . In Korea, the diagnosis of endometrial cancer has been steadily increasing over the last 10 years . Endometrial cancer is usually diagnosed at an early stage because patients present for consultations at the hospital with abnormal vaginal bleeding or discharge. The diagnosis is usually confirmed either by biopsy with endometrial curettage or hysteroscopy. The disease status is confirmed through imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]), and then the treatment method is determined. If the tumor is resectable, a surgery involving total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node (LN) dissection is performed. The adjuvant treatment option is chosen based on the pathologic report. Cancer may also be found incidentally in the ovaries in about 7% of the endometrial cancer patients . The tumor stages in such cases are dependent on whether it is a metastasis of an endometrial cancer, metastasis of an ovarian cancer, or a co-occurrence of both cancers in the ovaries and endometrium.
In 1985, Ulbright and Roth proposed criteria for distinguishing metastatic cancer (MC) from double primary cancer (DPC) in such cases . In 1998, Scully and Young proposed more detailed diagnostic criteria. Since the above criteria are widely used, there are many studies comparing the characteristics and prognoses in these two groups (MC and DPC) [6–17]. A prior study suggested that the prognosis was poor when metastasis involved other sites in addition to the uterus and ovaries and when there was no distinction between the DPC and MC . Endometrioid histology has been shown to have a better prognosis than non-endometrioid histology [8, 9]. Compared to DPC, MC has a poorer prognosis with cervical invasion, a large tumor size, and high-grade histology . Early-stage DPC showed a good prognosis in a study conducted only on DPC patients . Song et al. showed the association of the initial CA-125 level and ovarian stage with DPC survival , while Jain et al. showed the association between lymphovascular invasion and DPC survival . When comparing DPC with endometrial cancer, prognosis is not inferior than that in endometrial cancer . However, the prognosis in patients with cervical invasion, LN metastasis, and peritoneal dissemination, regardless of DPC or MC, is poor . Overall, the prognosis is good in early-stage DPC. It is difficult to accurately differentiate between DPC and MC based on these classical criteria or morphological differences including histopathology, size, and spread to adjacent organs.
On the one hand, in 2016, two independent studies reported that most synchronous endometrial and ovarian cancers (SEOCs) were single primary tumors with metastases; this was evaluated using massively parallel sequencing [18, 19]. Accordingly, Chao et al. analyzed 16 SEOC patients with massively parallel sequencing and copy number analysis . These studies support the fact that SEOC is a metastatic disease and not a DPC. However, it is difficult to apply these results in real-world clinical settings, because of high cost and long time needed for analysis.
On the other hand, categorization of the tumor as either DPC or MC is important for accurate diagnosis. However, determining the appropriate treatment modality for patients diagnosed with either DPC or MC is more important. If the diagnosis is DPC, each organ’s tumor is staged as IA; if the diagnosis is MC, the tumor is staged as IIIA based on the endometrial cancer staging or IIA based on the ovaries. It is thus important to know if the cancer occurs synchronously in the ovaries and endometrium or metastasizes from one organ to another. This helps to select patients who need adjuvant treatment, be it in the form of chemotherapy or radiotherapy. Therefore, we analyzed and compared the baseline characteristics of DPC and MC patients and analyzed the risk factors for recurrence.