Outcomes and prognostic factors in patients with synchronous endometrial and ovarian cancer.

Synchronous endometrial and ovarian cancer (SEOC), a rare dual-primary malignancy, requires further investigation into patient prognosis and its determinants. This study highlights the prognostic significance of ovarian tumor staging and platinum sensitivity in SEOC, underscoring the necessity for intensified postoperative surveillance and innovative therapeutic approaches for platinum-resistant cases.

We retrospectively analyzed patients with pathologically confirmed SEOC who received primary treatment at Peking University People’s Hospital between January 2004 and December 2024. The pathologic diagnostic criteria for SEOC were established by Young and Scully as follows [ 10 ]: (1) histologic dissimilarity of the tumors; (2) no or only superficial myometrial invasion of endometrial tumor; (3) no vascular space invasion of endometrial tumor; (4) atypical endometrial hyperplasia additionally present; (5) absence of other evidence of spread of endometrial tumor; (6) ovarian unilateral tumor (80–90% of cases); (7) ovarian tumor located in parenchyma; (8) no vascular space invasion, surface implants, or predominant hilar location in ovary; (9) absence of other evidence of spread of ovarian tumor; (10) ovarian endometriosis present; (11) different ploidy of DNA indices, if aneuploid, of the tumors; and (12) dissimilar molecular genetic or karyotypic abnormalities in the tumors. All patients received comprehensive preoperative imaging assessment to evaluate the feasibility of primary cytoreductive surgery. Prognosis was assessed via electronic medical records and telephone follow-up data. Cases with missing pathological reports or incomplete follow-up data were excluded. This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Peking University People’s Hospital (approval no. 2025PHB223-001). Demographic and clinicopathological characteristics, including age, menopausal status, presenting symptoms, BMI, family history of cancer, tumor stage, histological type and grade, lymph node metastasis, lymphovascular space invasion (LVSI), platinum sensitivity, PFS, and OS, were systematically extracted from medical records and telephonic follow-up. LVSI, defined by the presence of tumor cells within endothelial-lined lymphatic or blood vessels, is an established pathological marker of tumor aggressiveness and adverse prognosis in gynecological malignancies [ 13 , 14 ]. Platinum sensitivity is clinically defined as a platinum-free interval (PFI) of ≥ 6 months following completion of initial platinum-based chemotherapy before disease recurrence or progression. Conversely, platinum resistance denotes disease progression occurring within a PFI of < 6 months after primary platinum treatment [ 15 ]. PFS was defined as the interval from the date of surgical intervention to the first documented disease progression or death from any cause, whichever occurred first. Patients without documented progression or death at the time of data analysis were censored at their last follow-up date. OS was calculated from the date of primary surgery to the date of death from any cause, with surviving patients censored at the final follow-up. Surgical approaches vary across practitioners and include peritoneal cytology, pelvic and peritoneal biopsies, total hysterectomy (abdominal or laparoscopic), bilateral salpingo-oophorectomy, omentectomy, and pelvic/para-aortic lymph node sampling. Optimal cytoreductive surgery is defined by the presence of ≤ 1 cm macroscopic residual disease following surgical resection, as confirmed by intraoperative visual and tactile inspection [ 16 , 17 ]. Histopathological classification adhered to the World Health Organization (WHO) diagnostic criteria. All patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) criteria applicable at their diagnosis time. For instance, patients diagnosed before 2013 were classified using the 1988 FIGO ovarian cancer staging system, while those diagnosed in or after 2013 were staged with the revised 2013 FIGO criteria [ 18 , 19 ]. For endometrial carcinoma: staging was performed using the 1988, 2009, or 2023 FIGO classification systems, depending on the year of diagnosis [ 20 – 22 ]. Adjuvant therapy, including chemotherapy alone or a combination of maintenance therapy (e.g., targeted or hormonal agents), was administered to patients according to the pathological type, stage, age, nodal status, performance status, estrogen/progesterone receptor status, and comorbidities. No patients received radiotherapy in this study. The chemotherapy regimen consisted of paclitaxel (135–175 mg/m 2 ) plus carboplatin, with the carboplatin dose calculated using an area under the curve (AUC) of 5–6 and the glomerular filtration rate (GFR). Treatment cycles were repeated every 3–4 weeks, with dose adjustments based on the patient’s response and tolerance. A subset of patients with endometrioid histology and estrogen/progesterone receptor-positive status received hormonal therapy (e.g., medroxyprogesterone acetate 250 mg/day) for a duration of 1–2 years. Statistical analyses were conducted using IBM SPSS Statistics (version 26.0; IBM Corp., Armonk, NY, USA). The Shapiro–Wilk test assessed normality of continuous variables. Non-normally distributed continuous variables were analyzed using the Mann–Whitney U test, while categorical variables were compared with χ 2 tests (or Fisher’s exact test for cells with expected frequencies < 5). Time-dependent Cox proportional hazards regression models were employed to determine independent predictors of OS. Variables affecting PFS were first screened by univariate Cox analysis, with significant factors ( P  < 0.10) subsequently entered into multivariate models. Results are presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Survival distributions were compared using log-rank tests, and Kaplan–Meier curves were plotted. P  < 0.05 indicated statistical significance.

A total of 70 SEOC patients met the inclusion criteria, among whom six were excluded due to incomplete follow-up records or missing postoperative outcome data, yielding a final analytical cohort of 64 patients. The median age at diagnosis was 53 years (range 26–75). The most common presenting symptom was vaginal bleeding, including AUB and postmenopausal bleeding. Overweight or obesity (BMI ≥ 25 kg/m 2 ) was observed in 35 patients (54.7%), and 20 patients (31.3%) reported a family history of cancer. Baseline characteristics are detailed in Table  1 . Table 1 Clinical characteristics of SEOC patients Characteristics Category No. (%) or median (range) Age 53(26–75) Menopause 28(43.8) Symptom AUB 16(25) Postmenopausal bleeding 16(25) Pelvic mass 11(17.2) Abdominal distension/pain 19(29.7) BMI (kg/m 2 ) 25.1(16.6–33.9) Family history of cancer 20(31.3) CA-125 (U/ml) 112(10–5000) AUB abnormal vaginal bleeding, BMI body mass index, CA-125 cancer antigen 125 Clinical characteristics of SEOC patients AUB abnormal vaginal bleeding, BMI body mass index, CA-125 cancer antigen 125 Preoperative imaging confirmed resectability for optimal cytoreduction in all cases, and all 64 patients subsequently underwent primary debulking surgery. However, intraoperative evaluation revealed suboptimal cytoreduction in 2 patients due to severe adhesions or extensive pelvic abscesses, whereas the remaining 62 achieved optimal cytoreduction. In addition, suspicious hepatic surface lesions were identified in one further patient. Histopathological examination of the resected specimens confirmed metastatic carcinoma of ovarian origin, establishing a final diagnosis of FIGO stage IVB ovarian cancer. The pathological features of the tumors in the endometrial and ovarian regions were analyzed separately. For endometrial tumors, early stage (FIGO I/II) disease was identified in 60 patients (93.8%). Deep myometrial invasion (> 50%) was observed in 8 patients (12.5%), and high-grade lesions were present in 12 patients (18.8%). LVSI and cervical stromal invasion were documented in 6 (9.4%) and 4 patients (6.3%), respectively. For ovarian tumors, 44 patients (68.8%) were in an early stage (FIGO I/II), and high-grade lesions were found in 20 patients (31.3%). Endometrioid carcinoma was the most common concordant histologic type at both tumor sites and was observed in 36 patients (56.3%). Other histopathological subtypes were identified in 28 patients (43.8%). Among 64 patients, 56 (87.5%) received adjuvant platinum-based chemotherapy, of whom 38 (67.9%) demonstrated platinum sensitivity. Among the study cohort, five patients received hormonal therapy: four were treated with oral medroxyprogesterone acetate, and one received alternating cyclic therapy consisting of tamoxifen (20 mg/day for 3 weeks) followed by letrozole (2.5 mg/day for 3 weeks), repeated cyclically. Disease recurrence or progression occurred in 25 patients (39.1%) of the cohort, with a median recurrence-free interval of 8 months (range 3–36). Deaths were recorded in 24 patients (37.5%), with a median survival time of 20 months (range 7–87). The median PFS and OS were 27 months (range 3–215) and 41 months (range 7–246), respectively. Detailed clinicopathological outcomes are presented in Table  2 . Table 2 Pathological characteristics and prognosis of SEOC patients Characteristics Category No. (%) or median (range) Endometrial carcinoma FIGO stage IA 56(87.5) IB 4(6.3) IIIA 1(1.6) IIIC 1(1.6) IVB 2(3.1) Myometrial invasion < 1/2 56(87.5) ≥ 1/2 8(12.5) Endometrial pathological grade low 52(81.3) high 12(18.8) LVSI of endometrial lesions Yes 6(9.4) No 51(79.7) Cervical stromal invasion Yes 4(6.3) No 54(84.4) Ovarian carcinoma FIGO stage IA 19(29.7) IC1 6(9.4) IC2 7(10.9) IC3 4(6.3) IIB 8(12.5) IIIA 1(1.6) IIIB 5(7.8) IIIC 13(20.3) IVB 1(1.6) Ovarian pathological grade low 43(67.2) high 20(31.3) Lymph node metastasis Yes 1(1.6) No 60(93.8) Histologic type Endometrioid/endometrioid 36(56.3) Endometrioid/Serous 7(10.9) Serous/Serous 3(4.7) Others 18(28.1) Adjuvant therapy None 8(12.5) Chemotherapy 56(87.5) platinum sensitivity Platinum sensitive 38(67.9) Platinum insensitive 13(23.2) Unknown 5(8.9) PFS (month) – 27(3–215) OS (month) – 41(7–246) LVSI lymphovascular space invasion, PFS progression-free survival, OS overall survival Pathological characteristics and prognosis of SEOC patients LVSI lymphovascular space invasion, PFS progression-free survival, OS overall survival Univariate and multivariate Cox regression analyses of clinicopathological variables associated with survival outcomes are summarized in Table  3 . Previous studies have demonstrated that disease stage significantly influences patient prognosis [ 10 ]. To further investigate the differential prognostic impact of tumor site-specific FIGO stage (endometrial or ovarian) on survival outcomes in SEOC, stratified analyses of disease staging were performed for endometrial and ovarian tumors independently. Table 3 Prognostic factors associated with PFS and OS Progression-free survival Overall survival Univariate Multivariate Univariate Multivariate HR (95% CI) P* HR (95% CI) P* HR (95% CI) P # HR (95% CI) P # Myometrial invasion 0.015 0.926 0.019 0.758  < 1/2 1 1 1 1  ≥ 1/2 3.150 (1.247–7.956) 0.930 (0.202–4.287) 3.055 (1.204–7.748) 1.298 (0.248–6.804) EC FIGO stage 0.001 0.058 0.000 0.617  Early 1 1 1 1  Advanced 8.124 (2.494–26.462) 5.655 (0.940–34.024) 9.686 (2.945–31.858) 2.140 (0.108–42.384) EC pathological grade 0.118 – – 0.045 0.862  Low 1 1 1  High 1.955 (0.844–4.533) 2.331 (1.019–5.333) 0.897 (0.263–3.056) OC FIGO stage 0.001 0.021 0.001 0.111  Early 1 1 1 1  Advanced 3.982 (1.782–8.894) 2.764 (1.169–6.536) 4.175 (1.824–9.552) 2.599 (0.802–8.421) OC pathological grade 0.006 0.101 0.001 0.182  Low 1 1 1 1  High 3.136 (1.391–7.068) 2.104 (0.866–5.115) 4.280 (1.812–10.112) 2.405 (0.663–8.731) LVSI 0.496 – – 0.181 – –  No 1 1  Yes 1.524 (0.454–5.116) 0.843 (0.197–3.605) Lymph node metastasis 0.114 – – 0.018 0.537  No 1 1 1  Yes 5.262 (0.673–41.132) 13.994 (1.564–125.217) 2.897 (0.099–84.514) Platinum sensitive – – – – 0.000 0.002  Yes – – – – 1 1  No – – – – 11.612 (4.094–32.940) 6.962 (2.052–23.619) EC endometrial cancer, OC ovarian cancer, LVSI lymphovascular space invasion * Univariate and multivariate COX regression analyses were performed # Time-dependent Cox regression analyses was performed Bold values indicate statistically significant differences ( p ＜0.05) Prognostic factors associated with PFS and OS 3.150 (1.247–7.956) 0.930 (0.202–4.287) 3.055 (1.204–7.748) 1.298 (0.248–6.804) 8.124 (2.494–26.462) 5.655 (0.940–34.024) 9.686 (2.945–31.858) 2.140 (0.108–42.384) 1.955 (0.844–4.533) 2.331 (1.019–5.333) 0.897 (0.263–3.056) 3.982 (1.782–8.894) 2.764 (1.169–6.536) 4.175 (1.824–9.552) 2.599 (0.802–8.421) 3.136 (1.391–7.068) 2.104 (0.866–5.115) 4.280 (1.812–10.112) 2.405 (0.663–8.731) 1.524 (0.454–5.116) 0.843 (0.197–3.605) 5.262 (0.673–41.132) 13.994 (1.564–125.217) 2.897 (0.099–84.514) 11.612 (4.094–32.940) 6.962 (2.052–23.619) EC endometrial cancer, OC ovarian cancer, LVSI lymphovascular space invasion * Univariate and multivariate COX regression analyses were performed # Time-dependent Cox regression analyses was performed Bold values indicate statistically significant differences ( p ＜0.05) In the univariate analysis, the depth of myometrial invasion (> 50%), FIGO stage of ovarian cancer, FIGO stage of endometrial cancer, and ovarian tumor grade were significantly associated with PFS. Multivariate Cox regression identified advanced FIGO stage of ovarian cancer (HR = 2.764; 95% CI 1.169–6.536; P  = 0.021) as an independent risk factor for reduced PFS. For OS, univariate time-dependent Cox analysis revealed significant associations with depth of myometrial invasion, FIGO stage of ovarian and endometrial cancer, histological grading of ovarian and endometrial tumors, lymph node metastasis, and platinum sensitivity. Multivariate analysis revealed that platinum resistance (HR = 6.962; 95% CI 2.052–23.619; P  = 0.002) was an independent predictor of poor OS. K‒M survival curves for PFS and OS are shown in Figs. 1 and 2 , respectively. Fig. 1 Progression-free survival of all patients when grouped according to FIGO staging of ovarian caner Fig. 2 Overall survival of all patients when grouped according to platinum sensitivity Progression-free survival of all patients when grouped according to FIGO staging of ovarian caner Overall survival of all patients when grouped according to platinum sensitivity

Although SEOC is a rare clinical entity with an estimated incidence of 0.63–1.7% [ 1 ], a recent population-based study suggested that its prevalence among epithelial ovarian cancer patients is increasing [ 23 ]. To characterize the clinicopathological profile and prognostic determinants of SEOC, we retrospectively analyzed 64 patients. The clinicopathological features were consistent with previous reports: AUB and postmenopausal bleeding were the most frequent clinical presentations, more than half of the patients were diagnosed at an early stage, and endometrioid carcinoma represented the predominant histopathological type [ 10 , 11 , 24 ]. Notably, 31.3% of patients reported a family history of cancer—a potentially clinically significant indicator not previously emphasized in SEOC studies. SEOC is generally associated with a favorable prognosis and is characterized by low mortality [ 25 ] and a 5-year survival rate of 69–86% [ 10 , 11 , 26 ]. In this cohort, the median PFS and OS were 27 months and 41 months, respectively. The molecular subtype of endometrial cancer has been established as a prognostic determinant [ 27 ]. In SEOC, homologous recombination deficiency (HRD) gene panel analyses have identified distinct genomic alterations. Notably, ATM mutations were the most frequent somatic alterations, with preliminary evidence suggesting their potential association with improved survival outcomes [ 28 ]. Molecular studies have demonstrated clonal relatedness in most SEOC cases, with shared genomic alterations strongly supporting a monoclonal origin from endometrial primary tumors [ 7 , 29 ]. However, clinicopathological comparisons between SEOC and metastatic carcinomas by Wang et al. revealed no significant differences in clinical factors or survival outcomes between the two groups, underscoring the need for tailored adjuvant therapy in high-risk patients [ 24 ]. In a mortality analysis of SEOC patients, Robert et al. reported that this cohort showed lower age-adjusted mortality rates compared to patients with stage IIIA endometrial cancer, stage I endometrial cancer, and stage I ovarian cancer. Their findings indicate that misclassification of stage IIIA uterine cancer as SEOC under current diagnostic criteria is rare. The significantly higher overall survival—even after adjusting for age, year, stage, grade, histology, and adjuvant treatment—does not justify modifications to current diagnostic or therapeutic guidelines [ 25 ]. Subgroup analyses based on histologic subtypes revealed no significant survival disparities between endometrioid/endometrioid and other subtypes [ 30 , 31 ]. Similarly, Ulas et al. reported comparable survival rates across histologic types but identified advanced FIGO stage and LVSI as independent prognostic factors [ 10 ]. Chiang et al. [ 4 ] and Liu et al. [ 32 ] showed that tumor stage had a greater prognostic impact than histologic subtype. In the study by Niloufar Hoorshad et al., univariate analysis revealed that higher tumor grade and advanced FIGO stage of ovarian cancer were significantly associated with worse PFS. However, multivariate analysis identified LVSI as the only independent predictor of poor PFS [ 33 ]. To delineate site-specific prognostic effects, we analyzed the staging of endometrial and ovarian tumors separately. Our univariate findings similarly demonstrated significant associations between ovarian cancer FIGO stage, tumor grade, and PFS. In contrast to their study, our multivariate analysis—after adjusting for potential confounders—still supported ovarian cancer FIGO stage as an independent prognostic factor for PFS(HR = 2.764; 95% CI 1.169–6.536; P  = 0.021). These results advocate for a comprehensive postoperative strategy that integrates stage-appropriate adjuvant therapy and intensified surveillance for recurrence, particularly in patients with advanced ovarian staging. LVSI has been identified not only as a factor associated with PFS [ 33 ], but also as an independent adverse prognostic factor for OS in the study by Ulas Solmaz et al. [ 10 ]. However, in our current study, neither univariate nor multivariate analysis revealed a significant association between LVSI and prognosis in patients with SEOC. This observed discrepancy likely reflects the limited statistical power in our LVSI-positive subgroup ( n  = 6), representing only 9.4% of the study cohort. Further investigation with larger sample sizes is required to clarify the prognostic impact of LVSI in SEOC patients. The SEOC treatment regimen consists of surgical resection, chemotherapy, and adjuvant radiotherapy, with optimal cytoreduction being a key determinant of prognosis [ 10 ]. In this cohort, optimal cytoreduction was achieved in 62 of 64 patients (96.9%). The two exceptions failed to achieve optimal cytoreduction due to unresectable pelvic abscesses or bulky adhesive tumors. Both patients developed disease progression postoperatively, succumbing to disease at 19 and 11 month post-diagnosis, respectively. These findings suggest that optimal cytoreduction is a critical prognostic determinant in patients with SEOC. To our knowledge, this is the first study to evaluate the prognostic significance of platinum sensitivity in SEOC. Among the 64 patients, 56 (87.5%) received postoperative platinum-based chemotherapy, with 38 (67.9%) demonstrating platinum sensitive. Univariate analysis identified multiple clinicopathological factors and adjuvant chemotherapy as significant predictors of OS. However, multivariate time-dependent Cox regression confirmed platinum sensitivity as the sole independent prognostic factor for OS. These findings emphasize the pivotal role of platinum-based chemotherapy in SEOC management. In support of this, Angel et al. [ 34 ] reported that copy number alteration (CNA) profiling in SEOC may stratify patients requiring adjuvant chemotherapy, highlighting the potential integration of molecular markers into therapeutic decision-making. This study has several limitations inherent to its retrospective design. First, the potential for unmeasured confounding factors could not be fully addressed because of the reliance on historical medical records. Second, treatment allocation bias may exist, as clinical decisions are influenced by individualized physician preferences rather than standardized protocols. In addition, heterogeneity in surgical techniques might introduce variability in outcome assessments. These limitations highlight the necessity of prospective multicenter studies with protocol-defined treatments to validate our findings. In summary, SEOC is predominantly diagnosed at an early stage and has a favorable prognosis. Our analysis identified the ovarian tumor FIGO stage as an independent predictor of PFS, underscoring the necessity of comprehensive surgical staging and optimized adjuvant therapy to improve PFS outcomes. Platinum sensitivity was independently associated with improved OS, warranting vigilant monitoring throughout chemotherapy and post-treatment surveillance. In platinum-resistant cases, exploration of novel therapeutic approaches is imperative to improve SEOC prognosis.

Synchronous primary malignancies of the female reproductive system are relatively rare, accounting for approximately 0.63–1.7% of all malignant tumors in this system. Among these, synchronous endometrial and ovarian cancer (SEOC) is the most common subtype, accounting for approximately 40–51.7% of cases [ 1 , 2 ]. Moreover, SEOC is also present in 3–10% of patients with ovarian malignancies and 3–5% of women with endometrial cancer [ 3 – 6 ]. In SEOC, the histological types may be concordant or discordant between the two sites, with endometrioid carcinoma being the most prevalent in both. Other subtypes, including mucinous, clear cell, and mixed-type carcinomas, may also occur [ 1 , 7 , 8 ]. SEOC patients are typically premenopausal women with higher body mass index (BMI) and nulliparity, while abnormal vaginal bleeding (AUB) represents the most common presenting symptom [ 9 , 10 ]. Currently, the treatment for SEOC includes surgery, adjuvant chemotherapy and radiotherapy [ 11 ]. SEOC has a relatively favorable prognosis, with a survival of approximately 10 years [ 9 ]. However, due to its low incidence [ 11 , 12 ], the clinical outcomes and prognostic factors still require further investigation. We conducted a retrospective cohort study at Peking University People’s Hospital to analyze the clinical data and treatment outcomes of patients diagnosed with SEOC. This study aimed to investigate the clinicopathological features, platinum-based chemotherapy efficacy, prognostic outcomes, and potential predictors of progression-free survival (PFS) and overall survival (OS) in these patients.