Impact of cytoreductive surgery on survival in advanced endometrial cancer: a 20- year retrospective cohort study

Impact of cytoreductive surgery on survival in advanced endometrial cancer: a 20- year retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of cytoreductive surgery on survival in advanced endometrial cancer: a 20- year retrospective cohort study Seda Biltekin, Gökçen Ege, Hasan Volkan Ege, Merve Saylık Çamöz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9112534/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Background The optimal extent of cytoreductive surgery in advanced-stage endometrial cancer remains controversial, and evidence is largely limited to small retrospective series with heterogeneous populations. This study aimed to evaluate the association between the extent of cytoreductive surgery and survival outcomes in a long-term single-center cohort of patients with advanced-stage EC. Methods Patients with FIGO stage IIIB–IV EC who underwent primary cytoreductive surgery between January 2000 and December 2020 were retrospectively analyzed. Cytoreductive status was classified as maximal (no macroscopic residual disease), optimal (≤ 1 cm residual disease), or suboptimal (> 1 cm residual disease). Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan–Meier method. Multivariable Cox proportional hazards regression was performed to identify independent prognostic factors. Results A total of 151 patients were included, of whom 57.0% achieved maximal cytoreduction, 35.8% optimal cytoreduction, and 7.3% suboptimal cytoreduction. The median OS for the entire cohort was 140.4 months (95% CI, 89.8–191.0), and the median DFS was 75.2 months (95% CI, 12.6–137.9). Median OS was not reached in the maximal cytoreduction group, whereas it was 50.2 months (95% CI, 11.0–89.4) and 10.2 months (95% CI, 3.7–16.6) in the optimal and suboptimal groups, respectively (log-rank p < 0.001). Median DFS was 188.5 months, 25.4 months, and 6.8 months, respectively (log-rank p < 0.001). In multivariable analysis, both optimal (HR 3.86, 95% CI 2.24–6.66) and suboptimal cytoreduction (HR 30.21, 95% CI 11.95–76.37) were independently associated with worse OS compared with maximal cytoreduction. Conclusion Maximal cytoreductive surgery was independently associated with improved overall and progression-free survival in patients with advanced-stage EC. These findings support maximal cytoreduction as a key surgical goal in appropriately selected patients managed by experienced multidisciplinary teams. Cytoreductive Surgery Endometrial Cancer Maximal Cytoreduction Overall Survival Progression-Free Survival Figures Figure 1 Figure 2 Figure 3 1. Background Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide, with a notable increase in incidence in developed countries [ 1 ]. This trend is primarily attributed to rising life expectancy, the increasing prevalence of obesity, and hormonal imbalances [ 2 ]. While the majority of EC cases are diagnosed at an early stage, approximately 20–30% present with advanced disease. Advanced-stage EC (International Federation of Gynecology and Obstetrics [FIGO] stage III–IV) is characterized by pelvic and para-aortic lymph node metastases, peritoneal dissemination, and distant organ involvement [ 3 ]. Although the FIGO classification was revised in 2023, the absence of immunohistochemical parameters in stage III–IV disease means that no significant changes were introduced for advanced-stage cases. Patients with advanced EC represent a group with more challenging clinical management and significantly reduced survival [ 4 ]. Treatment in this group requires a multimodal approach involving surgery, chemotherapy, and radiotherapy [ 5 ]. Among these, surgery is the cornerstone of primary disease control and survival improvement. Cytoreductive surgery aims to minimize tumor burden and enhance the efficacy of adjuvant therapies, with outcomes defined by the amount of residual disease. Cytoreduction is categorized as maximal (no visible residual disease), optimal (residual disease ≤ 1 cm), or suboptimal (residual disease > 1 cm) [ 6 ]. However, despite the established role of surgery, the central unresolved question in advanced-stage endometrial cancer is not whether cytoreductive surgery is beneficial, but rather the optimal extent of cytoreduction, particularly whether maximal cytoreduction provides a survival advantage over optimal or suboptimal resection. Although the survival benefit of cytoreduction is well established in ovarian cancer, evidence in EC remains limited and is mainly based on retrospective studies [ 7 , 8 ]. Therefore, evaluating the impact of cytoreduction levels on survival outcomes in advanced EC is of critical importance for determining optimal treatment strategies. Although the role of cytoreductive surgery in advanced-stage endometrial cancer remains controversial, recent population-based studies using large databases have provided increasing evidence supporting a survival benefit of surgery in selected patients. In a propensity score–matched analysis of patients with stage IVB endometrial cancer from the SEER database, cancer-directed surgery was associated with a significant improvement in overall survival, even when resection was limited to the primary tumour site [ 9 ]. However, the extent of cytoreduction and the patient subgroups most likely to benefit from aggressive surgery remain incompletely defined. Recent reports suggest that achieving no macroscopic residual disease through cytoreductive surgery may extend survival even in patients with stage IVB endometrial cancer with distant metastases [ 10 ]. Despite advances in surgical techniques and systemic therapy, the optimal extent of cytoreductive surgery in advanced-stage endometrial cancer remains uncertain. Most available evidence is derived from retrospective studies with heterogeneous patient populations and limited follow-up, often combining different disease stages and histological subtypes, while most prior studies have also focused on dichotomizing optimal versus suboptimal cytoreduction [ 6 , 7 , 11 ]. Consequently, the true prognostic impact of complete cytoreduction in long-term cohorts has not been fully clarified. The optimal management of FIGO stage IVB endometrial cancer remains challenging due to the heterogeneity of disease spread and the lack of high-level evidence [ 12 ]. A recent systematic review summarizing the available literature highlighted that, despite limited prospective data, optimal cytoreductive surgery consistently emerged as a key prognostic factor for survival, while the roles of neoadjuvant chemotherapy and adjuvant treatment strategies remain less clearly defined. In addition, surgical strategies, perioperative management, and adjuvant treatment protocols have evolved substantially over the past two decades. Therefore, long-term single-center cohorts with consistent surgical philosophy may offer valuable insights into survival outcomes. The present study aims to evaluate the association between the extent of cytoreductive surgery (maximal, optimal, and suboptimal) and survival outcomes in patients with advanced-stage endometrial cancer over a 20-year period. By restricting the cohort to stage IIIB–IV disease and performing detailed subgroup analyses, we sought to clarify the potential survival benefit of maximal cytoreduction while acknowledging the inherent limitations of retrospective observational data. This study analyzed overall survival (OS) and disease-free survival (DFS) in patients with advanced EC who underwent cytoreductive surgery at our center between 2000 and 2020, stratified by residual disease status (maximal, optimal, suboptimal). The findings aim to provide high-quality evidence to guide clinical practice regarding the therapeutic role of cytoreduction in advanced EC. 2. Methods This retrospective cohort study included patients with advanced-stage endometrial cancer who underwent primary cytoreductive surgery at a tertiary gynecologic oncology center between January 2000 and December 2020. Following institutional ethics committee approval (Approval No. 2022/155), medical records were retrospectively reviewed. 2.1. Patient Selection A total of 470 patients with endometrial cancer treated surgically between 2000 and 2020 were initially screened. After applying the predefined exclusion criteria, 151 patients with FIGO stage IIIB–IV disease who underwent primary cytoreductive surgery were included in the final analysis ( Fig. 1 ). Eligible patients included those with histologically confirmed EC, who underwent primary surgery and follow-up at our center, and had complete clinical data available. Patients with synchronous malignancies, stage I–IIIA disease, incomplete records, or loss to follow-up were excluded. The same specialized gynecologic oncology team performed all surgeries, and dedicated gynecopathologists conducted pathological evaluations. Patients with FIGO stage I–IIIA disease were excluded, as cytoreductive surgery is less relevant in earlier stages where complete tumor resection is routinely achievable, and survival outcomes are predominantly influenced by tumor biology rather than residual tumor burden. 2.1.1. Figure 1 : Flow diagram of patient selection Data collected included demographic characteristics (age, body mass index), date of diagnosis, surgical details (procedure, cytoreduction status, lymphadenectomy, additional organ resections), pathological findings (histological subtype, tumor grade, depth of myometrial invasion, presence of LVSI), FIGO stage (2009 and 2023), adjuvant treatment, recurrence status and date, survival status, and date of death (if applicable). Cytoreduction was categorized based on operative reports as maximal (no visible residual disease), optimal (≤ 1 cm residual disease), or suboptimal (> 1 cm residual disease). 2.2. Surgical Approach and Definition of Cytoreduction All patients underwent primary cytoreductive surgery at a tertiary gynecologic oncology center. Surgical procedures were performed by a specialized gynecologic oncology team; however, individual surgeons and operative strategies may have varied over the 20-year study period. The primary surgical goal was maximal tumor debulking whenever feasible, based on intraoperative assessment of disease distribution, patient performance status, and anticipated surgical morbidity. Cytoreductive status was classified based on the largest diameter of residual disease documented in operative reports: maximal (no macroscopic residual disease), optimal (≤ 1 cm residual disease), or suboptimal (> 1 cm residual disease). Although surgical techniques and perioperative management evolved over time, the definition of residual disease categories remained consistent throughout the study period. Although surgical techniques, perioperative management, and overall experience inevitably evolved over the 20-year study period, the fundamental surgical philosophy at our center consistently aimed to achieve maximal cytoreduction whenever technically feasible and clinically appropriate. Over time, advances in surgical expertise and multidisciplinary care may have facilitated a more aggressive surgical approach in selected patients. However, formal stratification or adjustment according to treatment era was not performed, and this temporal evolution represents a potential source of residual confounding. Follow-up was calculated as the interval between diagnosis and the last contact; for deceased patients, it was from diagnosis to death. DFS was defined as the time from surgery to recurrence or last follow-up, and OS as the time from surgery to death or last follow-up. 2.3. Statistical Analysis Statistical analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were expressed as numbers and percentages for categorical variables, and as mean, standard deviation, median, minimum, and maximum for continuous variables. Chi-square tests were used to compare categorical variables across cytoreduction groups. A multivariable Cox proportional hazards regression analysis was performed to identify independent prognostic factors associated with overall survival. Survival and recurrence outcomes were analyzed using the Kaplan-Meier method, and group comparisons were performed with the Log-Rank test. Statistical significance was defined as p < 0.05. 3. Results 3.1. Patient Characteristics A total of 151 patients with advanced-stage endometrial cancer were included in the study. The mean age was 58.5 ± 8.8 years (range, 33–78 years). The mean body mass index (BMI) was 33.4 ± 6.5 kg/m², and 70.2% (n=106) of patients were categorized as obese. The demographic and tumor-related characteristics of the patients are presented in Table 1 . Histopathological examination revealed endometrioid adenocarcinoma as the most common subtype, accounting for 60.9% (n=92), followed by serous carcinoma (16.6%, n=25), carcinosarcoma (13.2%, n=20), clear cell carcinoma (6.6%, n=10), and mixed type (2.6%, n=4). Tumor grading showed 47.7% (n=72) grade 3, 23.2% (n=35) grade 2, and 19.2% (n=29) grade 1 tumors. According to the 2009 FIGO staging system, 3.3% (n = 5) of patients were stage IIIB, 25.2% (n = 38) were stage IIIC1, 39.1% (n = 59) were stage IIIC2, and 32.5% (n = 49) were stage IVB. Using the 2023 FIGO classification, 25.2% (n=38) were stage IIIC1, 39.1% (n=59) stage IIIC2, 17.9% (n=27) stage IVB, and 14.6% (n=22) stage IVC. No stage IVA cases were identified in either classification. The median CA125 level was 51.5 U/mL, with a range of 1 to 1461 U/mL. 3.2. Surgical Procedures and Cytoreductive Status All patients underwent total hysterectomy (TH) and bilateral salpingo-oophorectomy (BSO). Depending on intraoperative findings, overall condition, and disease extent, bilateral pelvic and para-aortic lymph node dissection (BPPLND), omentectomy, gastrointestinal resections (including stomach, small intestine, appendix, and colon), splenectomy, and diaphragmatic resection were performed. Maximal CRS was achieved in 57% (n = 86), optimal in 35.8% (n = 54), and suboptimal in 7.3% (n = 11) of patients. Table 1. Patient and Disease Characteristics of Advanced-Stage Endometrial Cancer Patients Patient and Disease Characteristics Number (n) Percentage (%) Age <60 ≥60 89 62 58.9 41.1 BMI Normal Overweight Obese 14 31 106 9.3 20.5 70.2 Histology Endometrioid Serous Clear Cell Carcinosarcoma Mixed 92 25 10 20 4 60.9 16.6 6.6 13.2 2.6 FIGO 2009 Stage Stage 3B Stage 3C1 Stage 3C2 Stage 4A Stage 4B 5 38 59 0 49 3.3 25.2 39.1 0 32.5 FIGO 2023 Stage Stage 3B Stage 3C1 Stage 3C2 Stage 4A Stage 4B Stage 4C 5 38 59 0 27 22 3.3 25.2 39.1 0 17.9 14.6 Myometrial Invasion Unknown Confined to Endometrium 50% Invasion Serosal Invasion 13 9 31 76 22 8.6 6.0 20.5 50.3 14.6 Grade Unknown Grade 1 Grade 2 Grade 3 15 29 35 72 9.9 19.2 23.2 47.7 Tumor Size Mean ± SD 48.04 ± 23.91 51.5 (1-1461) CA-125 IU/mL Median (min–max) Age Median (min–max) 58 (33 - 78) 32.9 (19 - 53) BMI Median (min–max) BMI: Body Mass Index, Max.: Maximum, Min.: Minimum, SD: Standard Deviation. When histopathological findings were compared by CRS type, no significant difference in the distribution of tumor subtypes was observed (p = 0.074). In contrast, CRS groups differed significantly with respect to FIGO 2009 stage (p < 0.001), FIGO 2023 stage (p < 0.001), stage shift (p = 0.002) and depth of myometrial invasion (p = 0.002) (Stage shift defined as changes in individual patient staging when reclassified from FIGO 2009 to FIGO 2023 criteria). In both classifications, most patients in the maximal CRS group were stage IIIC1 (36.0%) or IIIC2 (39.5%), whereas stage IVB was notably higher in the suboptimal CRS group (63.6%). In the 2023 classification, stages IVB (36.4%) and IVC (27.3%) were more frequent in the suboptimal group, while stage IVB (11.6%) and IVC (7%) were rare in the maximal group. Details of the surgical procedures, histopathological findings, and their distribution across CRS subgroups are presented in Table 2 . Detailed information on individual additional surgical procedures is provided in Additional file 1 (Table S1). 3.3. Survival Outcomes According to Cytoreductive Surgery The median overall survival for the entire cohort was 140.4 months (95% CI, 89.8–191.0), and the median progression-free survival was 75.2 months (95% CI, 12.6–137.9) (log-rank p < 0.001). Overall survival was strongly associated with cytoreductive status. Median OS was not reached in the maximal CRS group, whereas it was 50.2 months (95% CI, 11.0–89.4) in the optimal CRS group and 10.2 months (95% CI, 3.7–16.6) in the suboptimal CRS group. Kaplan–Meier analysis demonstrated a significant difference in overall survival according to cytoreductive status (Fig. 2). The median follow-up time for the entire cohort was 69 months (range: 2–284 months), and 117.5 months (range: 3–284 months) for patients who achieved maximal cytoreduction. Table 2: Clinicopathological characteristics according to cytoreductive status, with detailed surgical procedures presented in Supplementary Table 1. Maximal (n:86) Optimal (n:54) Suboptimal (n:11) n % n % n % Patient and Disease Characteristics Age <60 ≥60 60 69.8 25 46.3 4 36.4 26 30.2 29 53.7 7 63.6 BMI Normal Overweight Obese 10 11.6 3 5.6 1 9.1 17 19.8 14 25.9 0 0.0 59 68.6 37 68.5 10 90.9 Clinical and Pathological Findings Histology Endometrioid Serous Clear Cell Carcinosarcoma Mixed 60 13 4 8 1 69.8 15.1 4.7 9.3 1.2 25 11 4 11 3 46.3 20.4 7.4 20.4 5.6 7 1 2 1 0 63.6 9.1 18.2 9.1 0.0 Grade Unknown Grade 1 Grade 2 Grade 3 7 46.6 4 26.7 4 26.7 22 75.9 7 24.1 0 0.0 24 68.6 10 28.6 1 2.8 33 45.8 33 45.8 6 8.4 FIGO 2009 Stage 3b 3c1 3c2 4b 5 5.8 0 0.0 0 0.0 31 36.0 6 11.1 1 9.1 34 39.5 22 40.7 3 27.3 16 18.6 26 48.1 7 63.6 FIGO 2023 Stage 3b 3c1 3c2 4a 4b 4c 5 5.8 0 0.0 0 0.0 31 36.0 6 11.1 1 9.1 34 39.5 22 40.7 3 27.3 0 0.0 0 0.0 0 0.0 10 11.6 13 24.1 4 36.4 6 7.0 13 24.1 3 27.3 Myometrial Invasion Unknown Confined to Endometrium 50% Invasion Serosal Invasion 6 7.0 4 7.4 3 27.3 0 0.0 7 13.0 2 18.2 21 24.4 8 14.8 2 18.2 49 57.0 23 42.6 4 36.4 10 11.6 12 22.2 0 0.0 Median (Min-Max) Median (Min-Max) Median (Min- Max) Tumor size H 45 (10 - 160) 40 (15 - 90) 40 (25 - 90) Lymph node count F 57.5 (4 - 120) a 51 (9 - 100) a 20 (0 - 89) b CA125 U/mL H 39.5 (1 - 1232) a 114.5 (6 - 1461) a 404.5 (16 - 1194) b F : One-Way ANOVA Test. H : Kruskal-Wallis H Test. Categorical data: Chi-Square Test (χ²). Lettering: Indicates the difference between groups. Max.: Maximum, Min.: Minimum. Progression-free survival differed significantly according to the extent of cytoreductive surgery. The median DFS was 188.5 months (95% CI, 155.4–221.5) in the maximal CRS group, compared with 25.4 months (95% CI, 14.9–35.9) in the optimal CRS group and 6.8 months (95% CI, 6.3–7.4) in the suboptimal CRS group. Progression-free survival also differed significantly among cytoreductive groups (log-rank p < 0.001, Fig. 3 ). 3.4. Recurrence and Post-Recurrence Outcomes Recurrence rates differed significantly by CRS type (p = 0.004). Most patients in the maximal CRS group remained recurrence-free (76.7%), whereas recurrence occurred in 46.3% of the optimal group and in all patients in the suboptimal group. A total of 55 patients experienced recurrence, with a median recurrence interval of 16 months (range, 1–242 months). Post-recurrence survival was markedly reduced in the suboptimal CRS group (3.5 months), compared with 41.1 months in the maximal group and 23.8 months in the optimal group. Data on treatment patterns at recurrence were not systematically available, precluding a comparative analysis of post-recurrence management between cytoreductive groups. 3.5. Multivariable Analysis of Prognostic Factors In multivariable Cox regression analysis, the extent of cytoreductive surgery remained independently associated with overall survival after adjustment for age, body mass index, FIGO stage, and histological subtype. The results of the multivariable Cox proportional hazards regression analysis are summarized in Table 3 . Using maximal cytoreduction as the reference category, optimal cytoreduction was associated with a significantly increased risk of mortality (HR 3.86, 95% CI 2.24–6.66, p<0.001), whereas suboptimal cytoreduction was associated with the poorest survival outcomes (HR 30.21, 95% CI 11.95–76.37, p<0.001). In addition, non-endometrioid histology was identified as an independent adverse prognostic factor (HR 3.04, 95% CI 1.75–5.29, p<0.001). In contrast, age, body mass index, and FIGO stage were not independently associated with overall survival in the multivariable model. Table 3. Multivariable Cox Regression Analysis of Factors Associated with Overall Survival Variable HR 95% CI p-value Age 1.03 0.99–1.06 0.071 BMI 1.01 0.97–1.05 0.48 FIGO Stage IV vs III 0.85 0.47–1.50 0.57 Histology Non-Endometrioid vs Endometrioid 3.04 1.75–5.29 <0.001 CRS Status Optimal vs Maximal Suboptimal vs Maximal 3.86 30.21 2.24–6.66 11.95–76.37 <0.001 <0.001 BMI: Body Mass Index; CI: Confidence Interval; CRS: Cytoreductive Surgery; FIGO: The International Federation of Gynecology and Obstetrics; HR: Hazard Ratio. 4. Discussion In this retrospective cohort study, maximal cytoreductive surgery was strongly associated with improved survival outcomes in patients with advanced-stage endometrial cancer. Our findings demonstrate that maximal CRS was associated with longer survival, whereas suboptimal surgery is strongly associated with markedly poor prognosis. The presence of residual tumor remains one of the most powerful prognostic factors. In the study by Ayhan et al . [ 7 ] involving 37 patients, the median survival was 48 months in stage IVB patients who underwent optimal CRS, compared with 10 months in those who underwent suboptimal CRS. Similarly, Chi et al. [ 13 ] reported that in stage IV endometrial cancer, median survival was 31 months in patients who underwent optimal CRS, versus 12 months in those who underwent suboptimal CRS. Shih et al. [ 14 ], in a retrospective study of 58 patients who underwent cytoreductive surgery for stage IV endometrioid endometrial cancer between 1977 and 2003, highlighted the significant survival advantage of maximal CRS. The mean survival was 42.2 months in patients without visible residual tumor, compared with 19 months in those with residual disease. Ayhan et al [ 7 ], in a study conducted between 1990 and 1998 in stage IVB endometrial cancer, demonstrated that optimal CRS was associated with a median survival of 34.3 months. In contrast, suboptimal CRS yielded only 11 months. These findings reinforce the concept that residual tumor status is among the strongest prognostic determinants. In our study, by categorizing maximal cytoreduction separately, we were able to demonstrate its substantial survival advantage more clearly. In our study, patients who underwent maximal CRS also demonstrated superior long-term survival, and post-recurrence survival was significantly longer. In contrast, the suboptimal group had higher recurrence rates and inferior post-recurrence survival (3.5 months). Our findings are consistent with recent large-scale retrospective analyses demonstrating a survival benefit of surgery in patients with stage IVB endometrial cancer. A population-based SEER study including nearly 2,000 propensity score–matched patients showed that cancer-directed surgery was independently associated with prolonged overall survival, even in the presence of distant metastases [ 9 ]. Notably, that study reported that almost all surgically treated patients underwent resection of the primary tumour, suggesting that removal of the uterine disease alone may confer a survival advantage, even when complete resection of metastatic sites is not feasible. Similarly, subgroup analyses of the SEER cohort indicated that younger patients and those with limited local tumour invasion (T1–T2) derived the most significant survival benefit from surgery. These findings closely mirror our results, in which maximal and optimal cytoreduction were more frequently achieved in patients with lower tumour burden and less extensive invasion. From a clinical decision-making perspective, our findings strongly support maximal cytoreduction as the preferred surgical goal in appropriately selected patients with advanced-stage endometrial cancer. Careful preoperative patient selection is essential to balance potential survival benefit against surgical morbidity. Preoperative imaging to assess disease distribution, evaluation of patient performance status, and biomarkers such as CA-125 may help identify patients most likely to benefit from aggressive cytoreductive surgery. Conversely, patients with extensive unresectable disease burden may be better managed with alternative strategies, such as neoadjuvant chemotherapy followed by interval debulking, to avoid futile surgical morbidity. Our findings are consistent with the conclusions of a recent systematic review on the management of stage IVB endometrial cancer, which identified optimal cytoreduction as the most consistent prognostic factor associated with improved survival across available studies [ 12 ]. That review also emphasized the potential role of neoadjuvant chemotherapy followed by interval debulking surgery in patients deemed unresectable at presentation, while reinforcing upfront surgery as the preferred approach whenever complete or optimal cytoreduction is feasible. In contrast to most studies included in the systematic review, which were limited by small sample sizes and short follow-up periods, the present study provides long-term survival data from a 20-year cohort, allowing a more robust evaluation of the prognostic impact of the extent of cytoreductive surgery. Our results resonate with contemporary evidence indicating that minimal residual disease after cytoreductive surgery confers a better prognosis in stage IVB endometrial cancer [ 10 ]. Notably, the independent association between cytoreductive status and survival persisted after adjustment for known prognostic factors, including stage and histological subtype. The lack of independent prognostic significance of FIGO stage in the multivariable model likely reflects collinearity between disease extent and the feasibility of achieving maximal cytoreduction. This overlap makes it difficult to separate the prognostic impact of stage from surgical outcome in retrospective cohorts. Although the 2023 FIGO staging system reflects a significant shift toward incorporating molecular features in early-stage disease, its impact on stage III–IV endometrial cancer remains limited. Molecular classification according to TCGA has emerged as a powerful prognostic tool; however, its absence in the present study reflects the cohort's retrospective nature and long inclusion period. Future studies that integrate molecular classification with surgical outcomes are warranted to individualize treatment strategies in advanced-stage disease better. It is important to emphasize that the observed survival differences among cytoreduction groups do not necessarily imply a direct causal relationship. Patients who undergo maximal cytoreduction are more likely to have less extensive disease and more favorable biological characteristics, which inherently confer a better prognosis. In our cohort, patients in the suboptimal cytoreduction group more frequently presented with advanced FIGO stages, supporting the possibility that disease burden rather than surgical aggressiveness alone contributed to inferior survival outcomes. Therefore, the results of this study should be interpreted as an association between the extent of cytoreduction and survival, rather than definitive evidence of causality. Although the retrospective nature of the study precludes definitive causal inference, the persistence of cytoreductive status as an independent prognostic variable after multivariable adjustment suggests that the extent of residual disease captures clinically relevant tumor burden beyond conventional staging parameters. 4.1. Limitations This study has several significant limitations. First, its retrospective single-center design carries an inherent risk of selection bias, limiting causal inference. Second, perioperative morbidity and complication data were not systematically collected, precluding a balanced assessment of survival benefit relative to surgical risk. Third, changes in surgical techniques, perioperative care, and adjuvant treatment protocols over the 20-year study period may have influenced survival outcomes independently of cytoreductive status. Additionally, molecular classification based on TCGA was unavailable, and histopathological assessment was performed by multiple pathologists over time, raising the possibility of interobserver variability. Molecular subtype, particularly p53-abnormal tumors, has emerged as a strong independent prognostic factor in advanced-stage endometrial cancer. The absence of molecular classification, therefore, represents an important unmeasured confounder, as observed survival differences may partially reflect underlying tumor biology rather than the extent of cytoreductive surgery alone. In addition, selection bias cannot be fully excluded, as patients with lower tumor burden are more likely to undergo maximal cytoreduction. Future studies integrating TCGA-based molecular classification with surgical and survival outcomes are essential to refine patient selection and to better individualize the aggressiveness of cytoreductive surgery. Finally, although subgroup analyses were performed, the limited sample sizes in specific histological subgroups precluded robust sensitivity analyses. 5. Conclusions In this 20-year single-center cohort, maximal cytoreductive surgery was strongly associated with improved survival outcomes in patients with advanced-stage endometrial cancer. Maximal cytoreduction was associated with significantly longer overall and progression-free survival across histological subtypes, whereas suboptimal surgery was associated with a markedly poorer prognosis. These findings support maximal cytoreduction as the primary surgical goal in the management of advanced-stage endometrial cancer. Abbreviations BMI Body mass index CRS Cytoreductive surgery DFS Disease-free survival EC Endometrial cancer FIGO International Federation of Gynecology and Obstetrics HR Hazard ratio OS Overall survival TCGA The Cancer Genome Atlas Declarations Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of Etlik Zübeyde Hanım Women’s Health Training and Research Hospital (approval number: 2022/155, dated 08 December 2022). All patients included in the study were treated at this institution during the study period. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Due to the retrospective nature of the study, the long study period, and the use of anonymized data, informed consent from individual patients was waived by the local Ethics Committee. Consent for Publication Not applicable. Availability of Data and Materials The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions, but are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding This research received no external funding. Authors’ Contributions SB contributed to data curation and project administration and drafted the original manuscript. GE contributed to the study's methodology and resources and critically revised the manuscript for important intellectual content. HVE performed the formal statistical analysis and supervised the analytical process. MSÇ contributed to data curation and project administration. SK contributed to project administration. VK contributed to the formal analysis and methodology and provided overall supervision of the study. All authors read and approved the final manuscript. Acknowledgments The authors would like to thank the clinical staff of Ankara Etlik City Hospital and Zübeyde Hanım Women’s Health Training and Research Hospital for their support in patient care and data collection. We also thank all colleagues who contributed to the preparation of this manuscript. Authors’ Information GE is a gynecologic oncologist at Ankara Etlik City Hospital specializing in advanced gynecologic malignancies and cytoreductive surgery. References Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249. Crosbie EJ, Kitson SJ, McAlpine JN, et al. Endometrial cancer. The Lancet. 2022;399:1412-1428. Berek JS, Matias‐Guiu X, Creutzberg C, et al. FIGO staging of endometrial cancer: 2023. International Journal of Gynecology & Obstetrics. 2023;162:383-394. 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Survival benefit of surgical treatment for patients with stage IVB endometrial cancer: A propensity score-matched SEER database analysis. Journal of Obstetrics and Gynaecology. 2023;43:2204937. Kanno M, Yunokawa M, Kurihara N, et al. Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis. Journal of Gynecologic Oncology. 2023;34:e77. Rajkumar S, Nath R, Lane G, et al. Advanced stage (IIIC/IV) endometrial cancer: role of cytoreduction and determinants of survival. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2019;234:26-31. Capozzi VA, Scarpelli E, De Finis A, et al. Optimal management for stage IVB endometrial cancer: a systematic review. Cancers. 2023;15:5123. Chi DS, Welshinger M, Venkatraman ES, et al. The role of surgical cytoreduction in stage IV endometrial carcinoma. Gynecologic oncology. 1997;67:56-60. Shih K, Yun E, Gardner G, et al. Surgical cytoreduction in stage IV endometrioid endometrial carcinoma. Gynecologic oncology. 2011;122:608-611. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 May, 2026 Reviewers agreed at journal 17 May, 2026 Reviewers agreed at journal 17 May, 2026 Reviewers agreed at journal 17 May, 2026 Reviews received at journal 15 May, 2026 Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviewers agreed at journal 12 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 29 Mar, 2026 Reviewers invited by journal 28 Mar, 2026 Editor invited by journal 17 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Submission checks completed at journal 16 Mar, 2026 First submitted to journal 13 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9112534","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614972113,"identity":"c959f425-7dd2-44fa-a024-cb47bc3085dd","order_by":0,"name":"Seda Biltekin","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Seda","middleName":"","lastName":"Biltekin","suffix":""},{"id":614972115,"identity":"7e08c9e2-9c7a-4152-a762-71d3bc16b8d6","order_by":1,"name":"Gökçen Ege","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYFACNijN3gAkDCxI0cJzAKRFghQtEglgkrAGefe2xA8fd9jY9Us+v7rhR4EEA397dwJeLYZnjh2WnHkmLXnm7Jyymz1Ah0mcObsBv5YZ6W3MvG2Hkw1u56Td4AFqMZDIJULL37b/yfY3z6Td/EOMFnmJtGPMjG0H7Awk2I/dJsoWA55jyZK9bckJEmdy2G7LGEjwEPSLfHub4YefbXb2/O3Hn91888dGjr+9l4AtByB0YgMDjwGIwYNXOdiWBghtD0wxDwiqHgWjYBSMgpEJAPBwSJiIWo3kAAAAAElFTkSuQmCC","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Gökçen","middleName":"","lastName":"Ege","suffix":""},{"id":614972117,"identity":"b07e65b0-4cbf-4589-8bd2-99fa04a6806f","order_by":2,"name":"Hasan Volkan Ege","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"Volkan","lastName":"Ege","suffix":""},{"id":614972119,"identity":"ad344813-b049-44aa-95f1-8e6b090e9651","order_by":3,"name":"Merve Saylık Çamöz","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Merve","middleName":"Saylık","lastName":"Çamöz","suffix":""},{"id":614972122,"identity":"07ea7a20-7bfc-41bd-9001-1a8e31791f35","order_by":4,"name":"Sevgi Koç","email":"","orcid":"","institution":"Etlik Zübeyde Hanım Kadın Hastalıkları Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Sevgi","middleName":"","lastName":"Koç","suffix":""},{"id":614972124,"identity":"fcfe8bf4-6930-4a0c-b2f1-21d6eb989bb4","order_by":5,"name":"Vakkas Korkmaz","email":"","orcid":"","institution":"Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Vakkas","middleName":"","lastName":"Korkmaz","suffix":""}],"badges":[],"createdAt":"2026-03-13 08:55:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9112534/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9112534/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106723907,"identity":"83377385-cb49-4cb5-9697-a5e055155bb2","added_by":"auto","created_at":"2026-04-12 18:20:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":99718,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9112534/v1/e0e7537b6797184285e93cc1.png"},{"id":106004416,"identity":"4f70f775-fbd5-4348-ba8a-5dbbf369fab5","added_by":"auto","created_at":"2026-04-02 10:30:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47688,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves for overall survival according to the extent of cytoreductive surgery.\u003c/strong\u003e Median OS was not reached in the maximal cytoreduction group, whereas it was 50.2 months in the optimal group and 10.2 months in the suboptimal group (log-rank p \u0026lt; 0.001). Numbers at risk are displayed below the curves. Corresponding 95% confidence intervals for median survival are provided in the text. Median follow-up duration for the cohort was 69 months.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9112534/v1/f5343a2ee2a409dadb4e28cc.png"},{"id":106004417,"identity":"289d83b7-c656-4990-bd05-5f696fbdee8b","added_by":"auto","created_at":"2026-04-02 10:30:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46682,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves for progression-free survival according to the extent of cytoreductive surgery.\u003c/strong\u003eMedian PFS was 188.5 months in the maximal cytoreduction group, compared with 25.4 months in the optimal group and 6.8 months in the suboptimal group (log-rank p \u0026lt; 0.001). Numbers at risk are displayed below the curves. Corresponding 95% confidence intervals for median progression-free survival are provided in the text.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9112534/v1/6b939db94005ebb5db311b34.png"},{"id":106725399,"identity":"ab229c19-3933-4266-8fc2-e0d6d8f9ddd2","added_by":"auto","created_at":"2026-04-12 18:32:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1009799,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9112534/v1/8775c617-281b-48bd-b1f0-d9bf2d45aa66.pdf"},{"id":106004414,"identity":"0743d4c6-5c16-47ce-b43c-a6d149d21c0a","added_by":"auto","created_at":"2026-04-02 10:30:53","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":13847,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9112534/v1/5c4b322410e371ba7d5820a2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of cytoreductive surgery on survival in advanced endometrial cancer: a 20- year retrospective cohort study","fulltext":[{"header":"1. Background","content":"\u003cp\u003eEndometrial cancer (EC) is one of the most common gynecological malignancies worldwide, with a notable increase in incidence in developed countries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This trend is primarily attributed to rising life expectancy, the increasing prevalence of obesity, and hormonal imbalances [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile the majority of EC cases are diagnosed at an early stage, approximately 20\u0026ndash;30% present with advanced disease. Advanced-stage EC (International Federation of Gynecology and Obstetrics [FIGO] stage III\u0026ndash;IV) is characterized by pelvic and para-aortic lymph node metastases, peritoneal dissemination, and distant organ involvement [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although the FIGO classification was revised in 2023, the absence of immunohistochemical parameters in stage III\u0026ndash;IV disease means that no significant changes were introduced for advanced-stage cases. Patients with advanced EC represent a group with more challenging clinical management and significantly reduced survival [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Treatment in this group requires a multimodal approach involving surgery, chemotherapy, and radiotherapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among these, surgery is the cornerstone of primary disease control and survival improvement.\u003c/p\u003e \u003cp\u003eCytoreductive surgery aims to minimize tumor burden and enhance the efficacy of adjuvant therapies, with outcomes defined by the amount of residual disease. Cytoreduction is categorized as maximal (no visible residual disease), optimal (residual disease\u0026thinsp;\u0026le;\u0026thinsp;1 cm), or suboptimal (residual disease\u0026thinsp;\u0026gt;\u0026thinsp;1 cm) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, despite the established role of surgery, the central unresolved question in advanced-stage endometrial cancer is not whether cytoreductive surgery is beneficial, but rather the optimal extent of cytoreduction, particularly whether maximal cytoreduction provides a survival advantage over optimal or suboptimal resection. Although the survival benefit of cytoreduction is well established in ovarian cancer, evidence in EC remains limited and is mainly based on retrospective studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, evaluating the impact of cytoreduction levels on survival outcomes in advanced EC is of critical importance for determining optimal treatment strategies. Although the role of cytoreductive surgery in advanced-stage endometrial cancer remains controversial, recent population-based studies using large databases have provided increasing evidence supporting a survival benefit of surgery in selected patients. In a propensity score\u0026ndash;matched analysis of patients with stage IVB endometrial cancer from the SEER database, cancer-directed surgery was associated with a significant improvement in overall survival, even when resection was limited to the primary tumour site [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the extent of cytoreduction and the patient subgroups most likely to benefit from aggressive surgery remain incompletely defined. Recent reports suggest that achieving no macroscopic residual disease through cytoreductive surgery may extend survival even in patients with stage IVB endometrial cancer with distant metastases [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite advances in surgical techniques and systemic therapy, the optimal extent of cytoreductive surgery in advanced-stage endometrial cancer remains uncertain. Most available evidence is derived from retrospective studies with heterogeneous patient populations and limited follow-up, often combining different disease stages and histological subtypes, while most prior studies have also focused on dichotomizing optimal versus suboptimal cytoreduction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consequently, the true prognostic impact of complete cytoreduction in long-term cohorts has not been fully clarified. The optimal management of FIGO stage IVB endometrial cancer remains challenging due to the heterogeneity of disease spread and the lack of high-level evidence [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA recent systematic review summarizing the available literature highlighted that, despite limited prospective data, optimal cytoreductive surgery consistently emerged as a key prognostic factor for survival, while the roles of neoadjuvant chemotherapy and adjuvant treatment strategies remain less clearly defined.\u003c/p\u003e \u003cp\u003eIn addition, surgical strategies, perioperative management, and adjuvant treatment protocols have evolved substantially over the past two decades. Therefore, long-term single-center cohorts with consistent surgical philosophy may offer valuable insights into survival outcomes.\u003c/p\u003e \u003cp\u003eThe present study aims to evaluate the association between the extent of cytoreductive surgery (maximal, optimal, and suboptimal) and survival outcomes in patients with advanced-stage endometrial cancer over a 20-year period. By restricting the cohort to stage IIIB\u0026ndash;IV disease and performing detailed subgroup analyses, we sought to clarify the potential survival benefit of maximal cytoreduction while acknowledging the inherent limitations of retrospective observational data.\u003c/p\u003e \u003cp\u003eThis study analyzed overall survival (OS) and disease-free survival (DFS) in patients with advanced EC who underwent cytoreductive surgery at our center between 2000 and 2020, stratified by residual disease status (maximal, optimal, suboptimal). The findings aim to provide high-quality evidence to guide clinical practice regarding the therapeutic role of cytoreduction in advanced EC.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis retrospective cohort study included patients with advanced-stage endometrial cancer who underwent primary cytoreductive surgery at a tertiary gynecologic oncology center between January 2000 and December 2020. Following institutional ethics committee approval (Approval No. 2022/155), medical records were retrospectively reviewed.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Patient Selection\u003c/h2\u003e \u003cp\u003eA total of 470 patients with endometrial cancer treated surgically between 2000 and 2020 were initially screened. After applying the predefined exclusion criteria, 151 patients with FIGO stage IIIB\u0026ndash;IV disease who underwent primary cytoreductive surgery were included in the final analysis \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Eligible patients included those with histologically confirmed EC, who underwent primary surgery and follow-up at our center, and had complete clinical data available. Patients with synchronous malignancies, stage I\u0026ndash;IIIA disease, incomplete records, or loss to follow-up were excluded. The same specialized gynecologic oncology team performed all surgeries, and dedicated gynecopathologists conducted pathological evaluations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients with FIGO stage I\u0026ndash;IIIA disease were excluded, as cytoreductive surgery is less relevant in earlier stages where complete tumor resection is routinely achievable, and survival outcomes are predominantly influenced by tumor biology rather than residual tumor burden.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003e2.1.1. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e: Flow diagram of patient selection\u003c/h2\u003e \u003cp\u003eData collected included demographic characteristics (age, body mass index), date of diagnosis, surgical details (procedure, cytoreduction status, lymphadenectomy, additional organ resections), pathological findings (histological subtype, tumor grade, depth of myometrial invasion, presence of LVSI), FIGO stage (2009 and 2023), adjuvant treatment, recurrence status and date, survival status, and date of death (if applicable). Cytoreduction was categorized based on operative reports as maximal (no visible residual disease), optimal (\u0026le;\u0026thinsp;1 cm residual disease), or suboptimal (\u0026gt;\u0026thinsp;1 cm residual disease).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Surgical Approach and Definition of Cytoreduction\u003c/h2\u003e \u003cp\u003eAll patients underwent primary cytoreductive surgery at a tertiary gynecologic oncology center. Surgical procedures were performed by a specialized gynecologic oncology team; however, individual surgeons and operative strategies may have varied over the 20-year study period. The primary surgical goal was maximal tumor debulking whenever feasible, based on intraoperative assessment of disease distribution, patient performance status, and anticipated surgical morbidity.\u003c/p\u003e \u003cp\u003eCytoreductive status was classified based on the largest diameter of residual disease documented in operative reports: maximal (no macroscopic residual disease), optimal (\u0026le;\u0026thinsp;1 cm residual disease), or suboptimal (\u0026gt;\u0026thinsp;1 cm residual disease). Although surgical techniques and perioperative management evolved over time, the definition of residual disease categories remained consistent throughout the study period.\u003c/p\u003e \u003cp\u003eAlthough surgical techniques, perioperative management, and overall experience inevitably evolved over the 20-year study period, the fundamental surgical philosophy at our center consistently aimed to achieve maximal cytoreduction whenever technically feasible and clinically appropriate. Over time, advances in surgical expertise and multidisciplinary care may have facilitated a more aggressive surgical approach in selected patients. However, formal stratification or adjustment according to treatment era was not performed, and this temporal evolution represents a potential source of residual confounding.\u003c/p\u003e \u003cp\u003eFollow-up was calculated as the interval between diagnosis and the last contact; for deceased patients, it was from diagnosis to death. DFS was defined as the time from surgery to recurrence or last follow-up, and OS as the time from surgery to death or last follow-up.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Statistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were expressed as numbers and percentages for categorical variables, and as mean, standard deviation, median, minimum, and maximum for continuous variables. Chi-square tests were used to compare categorical variables across cytoreduction groups. A multivariable Cox proportional hazards regression analysis was performed to identify independent prognostic factors associated with overall survival. Survival and recurrence outcomes were analyzed using the Kaplan-Meier method, and group comparisons were performed with the Log-Rank test. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cem\u003e3.1. Patient Characteristics\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 151 patients with advanced-stage endometrial cancer were included in the study. The mean age was 58.5 \u0026plusmn; 8.8 years (range, 33\u0026ndash;78 years). The mean body mass index (BMI) was 33.4 \u0026plusmn; 6.5 kg/m\u0026sup2;, and 70.2% (n=106) of patients were categorized as obese. The demographic and tumor-related characteristics of the patients are presented in \u003cstrong\u003eTable 1\u003c/strong\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHistopathological examination revealed endometrioid adenocarcinoma as the most common subtype, accounting for 60.9% (n=92), followed by serous carcinoma (16.6%, n=25), carcinosarcoma (13.2%, n=20), clear cell carcinoma (6.6%, n=10), and mixed type (2.6%, n=4). Tumor grading showed 47.7% (n=72) grade 3, 23.2% (n=35) grade 2, and 19.2% (n=29) grade 1 tumors.\u003c/p\u003e\n\u003cp\u003eAccording to the 2009 FIGO staging system, 3.3% (n = 5) of patients were stage IIIB, 25.2% (n = 38) were stage IIIC1, 39.1% (n = 59) were stage IIIC2, and 32.5% (n = 49) were stage IVB. Using the 2023 FIGO classification, 25.2% (n=38) were stage IIIC1, 39.1% (n=59) stage IIIC2, 17.9% (n=27) stage IVB, and 14.6% (n=22) stage IVC. No stage IVA cases were identified in either classification. The median CA125 level was 51.5 U/mL, with a range of 1 to 1461 U/mL.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.2. Surgical Procedures and Cytoreductive Status\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent total hysterectomy (TH) and bilateral salpingo-oophorectomy (BSO). Depending on intraoperative findings, overall condition, and disease extent, bilateral pelvic and para-aortic lymph node dissection (BPPLND), omentectomy, gastrointestinal resections (including stomach, small intestine, appendix, and colon), splenectomy, and diaphragmatic resection were performed. Maximal CRS was achieved in 57% (n = 86), optimal in 35.8% (n = 54), and suboptimal in 7.3% (n = 11) of patients.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 614px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Patient and Disease Characteristics of Advanced-Stage Endometrial Cancer Patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 365px;\"\u003e\n \u003cp\u003e\u003cem\u003ePatient and Disease Characteristics\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cem\u003eNumber (n)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003ePercentage (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e\u0026lt;60\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026ge;60\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e58.9\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e41.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003cp\u003eObese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e20.5\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e70.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003cp\u003eEndometrioid\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSerous\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eClear Cell\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCarcinosarcoma\u003c/p\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e60.9\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e16.6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e6.6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e13.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e2.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eFIGO 2009 Stage\u003c/p\u003e\n \u003cp\u003eStage 3B\u003c/p\u003e\n \u003cp\u003eStage 3C1\u003c/p\u003e\n \u003cp\u003eStage 3C2\u003c/p\u003e\n \u003cp\u003eStage 4A\u003c/p\u003e\n \u003cp\u003eStage 4B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e3.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e25.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e39.1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e32.5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eFIGO 2023 Stage\u003c/p\u003e\n \u003cp\u003eStage 3B\u003c/p\u003e\n \u003cp\u003eStage 3C1\u003c/p\u003e\n \u003cp\u003eStage 3C2\u003c/p\u003e\n \u003cp\u003eStage 4A\u003c/p\u003e\n \u003cp\u003eStage 4B\u003c/p\u003e\n \u003cp\u003eStage 4C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e3.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e25.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e39.1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e17.9\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e14.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eMyometrial Invasion\u003c/p\u003e\n \u003cp\u003eUnknown\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eConfined to Endometrium\u003c/p\u003e\n \u003cp\u003e\u0026lt;50% Invasion\u003c/p\u003e\n \u003cp\u003e\u0026gt;50% Invasion\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Serosal Invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e8.6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e6.0\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e20.5\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e50.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e14.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.9\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e19.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e23.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e47.7\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eTumor Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 249px;\"\u003e\n \u003cp\u003e48.04 \u0026nbsp;\u0026plusmn; \u0026nbsp; \u0026nbsp; 23.91\u003c/p\u003e\n \u003cp\u003e51.5 (1-1461)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eCA-125 IU/mL\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMedian (min\u0026ndash;max)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMedian (min\u0026ndash;max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"bottom\" style=\"width: 249px;\"\u003e\n \u003cp\u003e58 (33 - 78)\u003c/p\u003e\n \u003cp\u003e32.9 (19 - 53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMedian (min\u0026ndash;max)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 614px;\"\u003e\n \u003cp\u003e\u003cem\u003eBMI: Body Mass Index, Max.: Maximum, Min.: Minimum, SD: Standard Deviation.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eWhen histopathological findings were compared by CRS type, no significant difference in the distribution of tumor subtypes was observed (p = 0.074). In contrast, CRS groups differed significantly with respect to FIGO 2009 stage (p \u0026lt; 0.001), FIGO 2023 stage (p \u0026lt; 0.001), stage shift (p = 0.002) and depth of myometrial invasion (p = 0.002) (Stage shift defined as changes in individual patient staging when reclassified from FIGO 2009 to FIGO 2023 criteria). In both classifications, most patients in the maximal CRS group were stage IIIC1 (36.0%) or IIIC2 (39.5%), whereas stage IVB was notably higher in the suboptimal CRS group (63.6%). In the 2023 classification, stages IVB (36.4%) and IVC (27.3%) were more frequent in the suboptimal group, while stage IVB (11.6%) and IVC (7%) were rare in the maximal group. Details of the surgical procedures, histopathological findings, and their distribution across CRS subgroups are presented in \u003cstrong\u003eTable 2\u003c/strong\u003e. Detailed information on individual additional surgical procedures is provided in Additional file 1 (Table S1).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.3. Survival Outcomes According to Cytoreductive Surgery\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe median overall survival for the entire cohort was 140.4 months (95% CI, 89.8\u0026ndash;191.0), and the median progression-free survival was 75.2 months (95% CI, 12.6\u0026ndash;137.9) (log-rank p \u0026lt; 0.001). Overall survival was strongly associated with cytoreductive status. Median OS was not reached in the maximal CRS group, whereas it was 50.2 months (95% CI, 11.0\u0026ndash;89.4) in the optimal CRS group and 10.2 months (95% CI, 3.7\u0026ndash;16.6) in the suboptimal CRS group. Kaplan\u0026ndash;Meier analysis demonstrated a significant difference in overall survival according to cytoreductive status \u003cstrong\u003e(Fig. 2).\u0026nbsp;\u003c/strong\u003eThe median follow-up time for the entire cohort was 69 months (range: 2\u0026ndash;284 months), and 117.5 months (range: 3\u0026ndash;284 months) for patients who achieved maximal cytoreduction.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 643px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e Clinicopathological characteristics according to cytoreductive status, with detailed surgical procedures presented in Supplementary Table 1.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMaximal\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n:86)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eOptimal\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n:54)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eSuboptimal\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n:11)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cem\u003ePatient and Disease Characteristics\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e\u0026lt;60\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026ge;60\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e69.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e46.3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e36.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e30.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e53.7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e63.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003cp\u003eObese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e11.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e5.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e19.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e25.9\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e68.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e68.5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e90.9\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cem\u003eClinical and Pathological Findings\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003cp\u003eEndometrioid\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSerous\u003c/p\u003e\n \u003cp\u003eClear Cell\u003c/p\u003e\n \u003cp\u003eCarcinosarcoma\u003c/p\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e69.8\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e15.1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e4.7\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e1.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e46.3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e20.4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e7.4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e20.4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e5.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e63.6\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e18.2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e9.1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e46.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e26.7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e26.7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e75.9\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e24.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e68.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e28.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e2.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e45.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e45.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e8.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eFIGO 2009 Stage\u003c/p\u003e\n \u003cp\u003e3b\u003c/p\u003e\n \u003cp\u003e3c1\u003c/p\u003e\n \u003cp\u003e3c2\u003c/p\u003e\n \u003cp\u003e4b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e39.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e22\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e40.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e27.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e26\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e48.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e63.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eFIGO 2023 Stage\u003c/p\u003e\n \u003cp\u003e3b\u003c/p\u003e\n \u003cp\u003e3c1\u003c/p\u003e\n \u003cp\u003e3c2\u003c/p\u003e\n \u003cp\u003e4a\u003c/p\u003e\n \u003cp\u003e4b\u003c/p\u003e\n \u003cp\u003e4c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e5.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e36.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e11.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e9.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e39.5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e40.7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e27.3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e11.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e24.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e36.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e7.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e24.1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e27.3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eMyometrial Invasion\u003c/p\u003e\n \u003cp\u003eUnknown\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eConfined to Endometrium\u003c/p\u003e\n \u003cp\u003e\u0026lt;50% Invasion\u003c/p\u003e\n \u003cp\u003e\u0026gt;50% Invasion\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Serosal Invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e7.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e7.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e27.3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e13.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e18.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e24.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e14.8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e18.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e57.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e42.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e36.4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cem\u003e11.6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e22.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMedian (Min-Max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMedian (Min-Max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMedian (Min- Max)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 217px;\"\u003e\n \u003cp\u003eTumor size\u003csup\u003eH\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e45 (10 - 160)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e40 (15 - 90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e40 (25 - 90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 217px;\"\u003e\n \u003cp\u003eLymph node count\u003csup\u003eF\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e57.5 (4 - 120)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e51 (9 - 100)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e20 (0 - 89)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 217px;\"\u003e\n \u003cp\u003eCA125 U/mL\u003csup\u003eH\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e39.5 (1 - 1232)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e114.5 (6 - 1461)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e404.5 (16 - 1194)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 643px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003csup\u003eF\u003c/sup\u003e: One-Way ANOVA Test. \u003csup\u003eH\u003c/sup\u003e: Kruskal-Wallis H Test. Categorical data: Chi-Square Test (\u0026chi;\u0026sup2;). Lettering: Indicates the difference between groups. Max.: Maximum, Min.: Minimum.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eProgression-free survival differed significantly according to the extent of cytoreductive surgery. The median DFS was 188.5 months (95% CI, 155.4\u0026ndash;221.5) in the maximal CRS group, compared with 25.4 months (95% CI, 14.9\u0026ndash;35.9) in the optimal CRS group and 6.8 months (95% CI, 6.3\u0026ndash;7.4) in the suboptimal CRS group. Progression-free survival also differed significantly among cytoreductive groups (log-rank p \u0026lt; 0.001, \u003cstrong\u003eFig. 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.4. Recurrence and Post-Recurrence Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eRecurrence rates differed significantly by CRS type (p = 0.004). Most patients in the maximal CRS group remained recurrence-free (76.7%), whereas recurrence occurred in 46.3% of the optimal group and in all patients in the suboptimal group. A total of 55 patients experienced recurrence, with a median recurrence interval of 16 months (range, 1\u0026ndash;242 months). Post-recurrence survival was markedly reduced in the suboptimal CRS group (3.5 months), compared with 41.1 months in the maximal group and 23.8 months in the optimal group. Data on treatment patterns at recurrence were not systematically available, precluding a comparative analysis of post-recurrence management between cytoreductive groups.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.5. Multivariable Analysis of Prognostic Factors\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn multivariable Cox regression analysis, the extent of cytoreductive surgery remained independently associated with overall survival after adjustment for age, body mass index, FIGO stage, and histological subtype. The results of the multivariable Cox proportional hazards regression analysis are summarized in \u003cstrong\u003eTable 3\u003c/strong\u003e. Using maximal cytoreduction as the reference category, optimal cytoreduction was associated with a significantly increased risk of mortality (HR 3.86, 95% CI 2.24\u0026ndash;6.66, p\u0026lt;0.001), whereas suboptimal cytoreduction was associated with the poorest survival outcomes (HR 30.21, 95% CI 11.95\u0026ndash;76.37, p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eIn addition, non-endometrioid histology was identified as an independent adverse prognostic factor (HR 3.04, 95% CI 1.75\u0026ndash;5.29, p\u0026lt;0.001). In contrast, age, body mass index, and FIGO stage were not independently associated with overall survival in the multivariable model.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"650\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 650px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eMultivariable Cox Regression Analysis of Factors Associated with Overall Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVariable\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.99\u0026ndash;1.06\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.97\u0026ndash;1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFIGO Stage\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIV vs III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.47\u0026ndash;1.50\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHistology\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNon-Endometrioid vs Endometrioid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.75\u0026ndash;5.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 255px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCRS Status\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOptimal vs Maximal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSuboptimal vs Maximal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.86\u003c/p\u003e\n \u003cp\u003e30.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.24\u0026ndash;6.66\u003c/p\u003e\n \u003cp\u003e11.95\u0026ndash;76.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 631px;\"\u003e\n \u003cp\u003e\u003cem\u003eBMI: Body Mass Index; CI: Confidence Interval; CRS: Cytoreductive Surgery; FIGO: The International Federation of Gynecology and Obstetrics; HR: Hazard Ratio.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this retrospective cohort study, maximal cytoreductive surgery was strongly associated with improved survival outcomes in patients with advanced-stage endometrial cancer. Our findings demonstrate that maximal CRS was associated with longer survival, whereas suboptimal surgery is strongly associated with markedly poor prognosis.\u003c/p\u003e \u003cp\u003eThe presence of residual tumor remains one of the most powerful prognostic factors. In the study by Ayhan \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] involving 37 patients, the median survival was 48 months in stage IVB patients who underwent optimal CRS, compared with 10 months in those who underwent suboptimal CRS. Similarly, Chi \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] reported that in stage IV endometrial cancer, median survival was 31 months in patients who underwent optimal CRS, versus 12 months in those who underwent suboptimal CRS. Shih \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], in a retrospective study of 58 patients who underwent cytoreductive surgery for stage IV endometrioid endometrial cancer between 1977 and 2003, highlighted the significant survival advantage of maximal CRS. The mean survival was 42.2 months in patients without visible residual tumor, compared with 19 months in those with residual disease. Ayhan \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], in a study conducted between 1990 and 1998 in stage IVB endometrial cancer, demonstrated that optimal CRS was associated with a median survival of 34.3 months. In contrast, suboptimal CRS yielded only 11 months. These findings reinforce the concept that residual tumor status is among the strongest prognostic determinants. In our study, by categorizing maximal cytoreduction separately, we were able to demonstrate its substantial survival advantage more clearly.\u003c/p\u003e \u003cp\u003eIn our study, patients who underwent maximal CRS also demonstrated superior long-term survival, and post-recurrence survival was significantly longer. In contrast, the suboptimal group had higher recurrence rates and inferior post-recurrence survival (3.5 months).\u003c/p\u003e \u003cp\u003eOur findings are consistent with recent large-scale retrospective analyses demonstrating a survival benefit of surgery in patients with stage IVB endometrial cancer. A population-based SEER study including nearly 2,000 propensity score\u0026ndash;matched patients showed that cancer-directed surgery was independently associated with prolonged overall survival, even in the presence of distant metastases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Notably, that study reported that almost all surgically treated patients underwent resection of the primary tumour, suggesting that removal of the uterine disease alone may confer a survival advantage, even when complete resection of metastatic sites is not feasible. Similarly, subgroup analyses of the SEER cohort indicated that younger patients and those with limited local tumour invasion (T1\u0026ndash;T2) derived the most significant survival benefit from surgery. These findings closely mirror our results, in which maximal and optimal cytoreduction were more frequently achieved in patients with lower tumour burden and less extensive invasion.\u003c/p\u003e \u003cp\u003eFrom a clinical decision-making perspective, our findings strongly support maximal cytoreduction as the preferred surgical goal in appropriately selected patients with advanced-stage endometrial cancer. Careful preoperative patient selection is essential to balance potential survival benefit against surgical morbidity. Preoperative imaging to assess disease distribution, evaluation of patient performance status, and biomarkers such as CA-125 may help identify patients most likely to benefit from aggressive cytoreductive surgery. Conversely, patients with extensive unresectable disease burden may be better managed with alternative strategies, such as neoadjuvant chemotherapy followed by interval debulking, to avoid futile surgical morbidity.\u003c/p\u003e \u003cp\u003eOur findings are consistent with the conclusions of a recent systematic review on the management of stage IVB endometrial cancer, which identified optimal cytoreduction as the most consistent prognostic factor associated with improved survival across available studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. That review also emphasized the potential role of neoadjuvant chemotherapy followed by interval debulking surgery in patients deemed unresectable at presentation, while reinforcing upfront surgery as the preferred approach whenever complete or optimal cytoreduction is feasible. In contrast to most studies included in the systematic review, which were limited by small sample sizes and short follow-up periods, the present study provides long-term survival data from a 20-year cohort, allowing a more robust evaluation of the prognostic impact of the extent of cytoreductive surgery.\u003c/p\u003e \u003cp\u003eOur results resonate with contemporary evidence indicating that minimal residual disease after cytoreductive surgery confers a better prognosis in stage IVB endometrial cancer [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, the independent association between cytoreductive status and survival persisted after adjustment for known prognostic factors, including stage and histological subtype. The lack of independent prognostic significance of FIGO stage in the multivariable model likely reflects collinearity between disease extent and the feasibility of achieving maximal cytoreduction. This overlap makes it difficult to separate the prognostic impact of stage from surgical outcome in retrospective cohorts.\u003c/p\u003e \u003cp\u003eAlthough the 2023 FIGO staging system reflects a significant shift toward incorporating molecular features in early-stage disease, its impact on stage III\u0026ndash;IV endometrial cancer remains limited. Molecular classification according to TCGA has emerged as a powerful prognostic tool; however, its absence in the present study reflects the cohort's retrospective nature and long inclusion period. Future studies that integrate molecular classification with surgical outcomes are warranted to individualize treatment strategies in advanced-stage disease better.\u003c/p\u003e \u003cp\u003eIt is important to emphasize that the observed survival differences among cytoreduction groups do not necessarily imply a direct causal relationship. Patients who undergo maximal cytoreduction are more likely to have less extensive disease and more favorable biological characteristics, which inherently confer a better prognosis. In our cohort, patients in the suboptimal cytoreduction group more frequently presented with advanced FIGO stages, supporting the possibility that disease burden rather than surgical aggressiveness alone contributed to inferior survival outcomes.\u003c/p\u003e \u003cp\u003eTherefore, the results of this study should be interpreted as an association between the extent of cytoreduction and survival, rather than definitive evidence of causality. Although the retrospective nature of the study precludes definitive causal inference, the persistence of cytoreductive status as an independent prognostic variable after multivariable adjustment suggests that the extent of residual disease captures clinically relevant tumor burden beyond conventional staging parameters.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Limitations\u003c/h2\u003e \u003cp\u003eThis study has several significant limitations. First, its retrospective single-center design carries an inherent risk of selection bias, limiting causal inference. Second, perioperative morbidity and complication data were not systematically collected, precluding a balanced assessment of survival benefit relative to surgical risk. Third, changes in surgical techniques, perioperative care, and adjuvant treatment protocols over the 20-year study period may have influenced survival outcomes independently of cytoreductive status.\u003c/p\u003e \u003cp\u003eAdditionally, molecular classification based on TCGA was unavailable, and histopathological assessment was performed by multiple pathologists over time, raising the possibility of interobserver variability. Molecular subtype, particularly p53-abnormal tumors, has emerged as a strong independent prognostic factor in advanced-stage endometrial cancer. The absence of molecular classification, therefore, represents an important unmeasured confounder, as observed survival differences may partially reflect underlying tumor biology rather than the extent of cytoreductive surgery alone. In addition, selection bias cannot be fully excluded, as patients with lower tumor burden are more likely to undergo maximal cytoreduction. Future studies integrating TCGA-based molecular classification with surgical and survival outcomes are essential to refine patient selection and to better individualize the aggressiveness of cytoreductive surgery. Finally, although subgroup analyses were performed, the limited sample sizes in specific histological subgroups precluded robust sensitivity analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn this 20-year single-center cohort, maximal cytoreductive surgery was strongly associated with improved survival outcomes in patients with advanced-stage endometrial cancer. Maximal cytoreduction was associated with significantly longer overall and progression-free survival across histological subtypes, whereas suboptimal surgery was associated with a markedly poorer prognosis. These findings support maximal cytoreduction as the primary surgical goal in the management of advanced-stage endometrial cancer.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCytoreductive surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisease-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEndometrial cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFIGO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Federation of Gynecology and Obstetrics\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTCGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe Cancer Genome Atlas\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics Approval and Consent to Participate\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Etlik Z\u0026uuml;beyde Hanım Women\u0026rsquo;s Health Training and Research Hospital (approval number: 2022/155, dated 08 December 2022). All patients included in the study were treated at this institution during the study period. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Due to the retrospective nature of the study, the long study period, and the use of anonymized data, informed consent from individual patients was waived by the local Ethics Committee.\u003c/p\u003e\n\u003cp\u003eConsent for Publication\u003c/p\u003e\n\u003cp\u003eNot applicable. \u003c/p\u003e\n\u003cp\u003eAvailability of Data and Materials\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; Contributions\u003c/p\u003e\n\u003cp\u003eSB contributed to data curation and project administration and drafted the original manuscript. GE contributed to the study\u0026apos;s methodology and resources and critically revised the manuscript for important intellectual content. HVE performed the formal statistical analysis and supervised the analytical process. MS\u0026Ccedil; contributed to data curation and project administration. SK contributed to project administration. VK contributed to the formal analysis and methodology and provided overall supervision of the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the clinical staff of Ankara Etlik City Hospital and Z\u0026uuml;beyde Hanım Women\u0026rsquo;s Health Training and Research Hospital for their support in patient care and data collection. We also thank all colleagues who contributed to the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; Information \u003c/p\u003e\n\u003cp\u003eGE is a gynecologic oncologist at Ankara Etlik City Hospital specializing in advanced gynecologic malignancies and cytoreductive surgery.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249.\u003c/li\u003e\n \u003cli\u003eCrosbie EJ, Kitson SJ, McAlpine JN, et al. Endometrial cancer. The Lancet. 2022;399:1412-1428.\u003c/li\u003e\n \u003cli\u003eBerek JS, Matias‐Guiu X, Creutzberg C, et al. FIGO staging of endometrial cancer: 2023. International Journal of Gynecology \u0026amp; Obstetrics. 2023;162:383-394.\u003c/li\u003e\n \u003cli\u003eOaknin A, Bosse T, Creutzberg C, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2022;33:860-877.\u003c/li\u003e\n \u003cli\u003eAbu-Rustum N, Yashar C, Arend R, et al. Uterine neoplasms, version 1.2023, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network. 2023;21:181-209.\u003c/li\u003e\n \u003cli\u003eBristow RE, Zerbe MJ, Rosenshein NB, et al. Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival. Gynecologic oncology. 2000;78:85-91.\u003c/li\u003e\n \u003cli\u003eAyhan A, Taskiran C, Celik C, et al. The influence of cytoreductive surgery on survival and morbidity in stage IVB endometrial cancer. International Journal of Gynecological Cancer. 2002;12:448-453.\u003c/li\u003e\n \u003cli\u003eAlbright BB, Monuszko KA, Kaplan SJ, et al. Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis. American journal of obstetrics and gynecology. 2021;225:237. e231-237. e224.\u003c/li\u003e\n \u003cli\u003eZhang Y, Hao Z, Yang S. Survival benefit of surgical treatment for patients with stage IVB endometrial cancer: A propensity score-matched SEER database analysis. Journal of Obstetrics and Gynaecology. 2023;43:2204937.\u003c/li\u003e\n \u003cli\u003eKanno M, Yunokawa M, Kurihara N, et al. Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis. Journal of Gynecologic Oncology. 2023;34:e77.\u003c/li\u003e\n \u003cli\u003eRajkumar S, Nath R, Lane G, et al. Advanced stage (IIIC/IV) endometrial cancer: role of cytoreduction and determinants of survival. European Journal of Obstetrics \u0026amp; Gynecology and Reproductive Biology. 2019;234:26-31.\u003c/li\u003e\n \u003cli\u003eCapozzi VA, Scarpelli E, De Finis A, et al. Optimal management for stage IVB endometrial cancer: a systematic review. Cancers. 2023;15:5123.\u003c/li\u003e\n \u003cli\u003eChi DS, Welshinger M, Venkatraman ES, et al. The role of surgical cytoreduction in stage IV endometrial carcinoma. Gynecologic oncology. 1997;67:56-60.\u003c/li\u003e\n \u003cli\u003eShih K, Yun E, Gardner G, et al. Surgical cytoreduction in stage IV endometrioid endometrial carcinoma. Gynecologic oncology. 2011;122:608-611.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cytoreductive Surgery, Endometrial Cancer, Maximal Cytoreduction, Overall Survival, Progression-Free Survival","lastPublishedDoi":"10.21203/rs.3.rs-9112534/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9112534/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe optimal extent of cytoreductive surgery in advanced-stage endometrial cancer remains controversial, and evidence is largely limited to small retrospective series with heterogeneous populations. This study aimed to evaluate the association between the extent of cytoreductive surgery and survival outcomes in a long-term single-center cohort of patients with advanced-stage EC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with FIGO stage IIIB\u0026ndash;IV EC who underwent primary cytoreductive surgery between January 2000 and December 2020 were retrospectively analyzed. Cytoreductive status was classified as maximal (no macroscopic residual disease), optimal (\u0026le;\u0026thinsp;1 cm residual disease), or suboptimal (\u0026gt;\u0026thinsp;1 cm residual disease). Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan\u0026ndash;Meier method. Multivariable Cox proportional hazards regression was performed to identify independent prognostic factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 151 patients were included, of whom 57.0% achieved maximal cytoreduction, 35.8% optimal cytoreduction, and 7.3% suboptimal cytoreduction. The median OS for the entire cohort was 140.4 months (95% CI, 89.8\u0026ndash;191.0), and the median DFS was 75.2 months (95% CI, 12.6\u0026ndash;137.9). Median OS was not reached in the maximal cytoreduction group, whereas it was 50.2 months (95% CI, 11.0\u0026ndash;89.4) and 10.2 months (95% CI, 3.7\u0026ndash;16.6) in the optimal and suboptimal groups, respectively (log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Median DFS was 188.5 months, 25.4 months, and 6.8 months, respectively (log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In multivariable analysis, both optimal (HR 3.86, 95% CI 2.24\u0026ndash;6.66) and suboptimal cytoreduction (HR 30.21, 95% CI 11.95\u0026ndash;76.37) were independently associated with worse OS compared with maximal cytoreduction.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMaximal cytoreductive surgery was independently associated with improved overall and progression-free survival in patients with advanced-stage EC. These findings support maximal cytoreduction as a key surgical goal in appropriately selected patients managed by experienced multidisciplinary teams.\u003c/p\u003e","manuscriptTitle":"Impact of cytoreductive surgery on survival in advanced endometrial cancer: a 20- year retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 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