Results
A total of 818 patients with AEOC are included in this study. Among them, 552 patients are in the PDS group, and 266 patients are in the NACT-IDS group. The NACT-IDS group exhibits a higher mean age ( P < 0.001) and a lower mean body weight ( P < 0.001) compared to the PDS group. Additionally, a greater proportion of patients with FIGO stage IV is observed in the NACT-IDS group than in the PDS group ( P < 0.001). Regarding pre-treatment marker levels, the NACT-IDS group exhibits lower CA125 levels, while serum total calcium and Suidan scores are higher relative to the PDS group ( Table 1 ). Table 1 Baseline Characteristics Comparison Between 818 AEOC Patients Undergoing PDS and NACT-IDS PDS (n=552) NACT-IDS (n=266) P Age (year) 56.54 (55.70 ~ 57.39) 58.99 (57.86 ~ 60.11) <0.001 Weight (kg) 62.54 (61.67 ~ 63.41) 58.80 (57.62 ~ 59.98) <0.001 Hypertension 0.649 Yes 131 (23.70%) 67 (25.20%) No 421 (76.30%) 199 (74.80%) Diabetes 0.641 Yes 48 (8.70%) 26 (9.80%) No 504 (91.30%) 240 (90.20%) CAD 0.817 Yes 35 (6.30%) 18 (6.80%) No 517 (93.70%) 248 (93.20%) History of Abdominal-Pelvic Surgery 0.340 Yes 178 (32.30%) 77 (28.90%) No 374 (67.80%) 189 (71.10%) Family History of OC 0.564 Yes 21 (3.80%) 8 (3.00%) No 531 (96.20%) 258 (97.00%) FIGO Stage <0.001 III 488 (88.40%) 201 (76.60%) IV 64 (11.60%) 65 (24.40%) Tumor Type Serous Carcinoma 504 (91.30%) 263 (98.90%) Mucinous Carcinoma 15 (2.70%) 0 (0.00%) Endometriosis Carcinoma 21 (3.80%) 2 (0.70%) Clear Cell Carcinoma 12 (2.20%) 1 (0.40%) CA125 (U/mL) 677.50 [323.50, 1640.50] 26.80 [135.85, 774.00] <0.001 CA153 (U/mL) 51.23 [23.35, 118.00] 55.28 [23.15, 142.00] 0.569 Albumin (g/L) 42.12 (41.80 ~ 42.44) 42.66 (42.18 ~ 43.14) 0.063 Serum Total Calcium (mmol/L) 2.31 (2.30 ~ 2.32) 2.33 (2.32 ~ 2.34) 0.003 Suidan Score 1.96 (1.84 ~ 2.07) 6.01 (5.71 ~ 6.31) <0.001 Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; FIGO, International Federation of Gynecology and Obstetrics; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153.
Baseline Characteristics Comparison Between 818 AEOC Patients Undergoing PDS and NACT-IDS
Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; FIGO, International Federation of Gynecology and Obstetrics; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153.
A comparison of perioperative factors between the two groups reveals several notable differences. The NACT-IDS group has a lower rate of intestinal resection (7.50% vs 12.30%, P = 0.038) and a higher rate of achieving R0 (56.40% vs 39.90%, P < 0.001) compared to the PDS group. Additionally, intraoperative blood loss is significantly reduced in the NACT-IDS group ( P = 0.002). Interestingly, at the follow-up endpoint, the median OS (Overall Survival) is 29 months for the NACT-IDS group versus 32 months for the PDS group, with the difference in OS being statistically significant ( P = 0.036). No statistically significant difference in PFS (Progression-free Survival) is observed between the two groups ( Table 2 ). Then, we conduct Cox regression analysis and Kaplan–Meier analysis to determine which treatment prolongs OS and to identify risk factors affecting survival in AEOC patients. Table 2 Analysis of Perioperative Factors and Survival Data in AEOC Patients of PDS Vs. NACT-IDS PDS (n=552) NACT-IDS (n=266) P Perioperative Factors Operation Time (hours) 2.75 [2.17, 3.67] 2.50 [1.83, 3.25] <0.001 Blood Loss (mL) 400.00 [200.00, 600.00] 300.00 [200.00, 500.00] 0.002 Blood Transfusion 0.685 Yes 224 (40.60%) 104 (39.10%) No 328 (59.40%) 162 (60.90%) Bowel Resection 0.038 Yes 68 (12.30%) 20 (7.50%) No 484 (87.70%) 246 (92.50%) R0 <0.001 Yes 220 (39.90%) 150 (56.40%) No 332 (60.10%) 116 (43.60%) Survival Data Analysis PFS (months) 22.00 [13.00, 35.50] 20.00 [13.00, 32.00] 0.367 OS (months) 32.00 [19.00, 54.00] 29.00 [19.00, 46.00] 0.036 Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; R0, No Macroscopic Residual Tumor After Surgery; PFS, Progression-Free Survival; OS, Overall Survival.
Analysis of Perioperative Factors and Survival Data in AEOC Patients of PDS Vs. NACT-IDS
Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; R0, No Macroscopic Residual Tumor After Surgery; PFS, Progression-Free Survival; OS, Overall Survival.
Cox regression analysis in the relationship between prognostic factors and OS in 818 patients with AEOC are presented in Table 1 . Among prognostic factors, age ( P = 0.009), CA153 ( P = 0.004), serum total calcium ( P = 0.006), and Non-R0 ( P < 0.001) are independent risk factors for OS. Family history of OC (95% CI: 0.10 ~ 0.93, P = 0.038) and albumin (95% CI: 0.89 ~ 0.96, P < 0.001) are identified as protective factors ( Table 3 ). Notably, OS does not differ significantly among patients with treatment (PDS vs. NACT-IDS) ( P = 0.221, Table 3 ), which is consistent with the results of the Kaplan–Meier analysis ( P = 0.494, Figure 1A ). Patients with R0 show a considerably longer OS than those with R1/R2 ( P < 0.001, Figure 1B ), whether based on PDS group ( P < 0.001, Figure 1C ) or NACT-IDS group ( P = 0.005, Figure 1D ). Table 3 Cox Regression Analysis of Prognostic Factors for OS in 818 Patients with AEOC Variables Univariate Cox Regression Multivariate Cox Regression SE 95.0% CI P SE 95.0% CI P Age (year) 0.02 0.98 ~ 1.08 0.228 0.01 1.00 ~ 1.03 0.009 Weight (kg) 0.02 0.96 ~ 1.05 0.958 0.01 0.99 ~ 1.01 0.836 Treatment (PDS vs NACT-IDS) 0.51 0.14 ~1.02 0.054 0.14 0.91 ~ 1.54 0.221 Hypertension (No/ Yes) 0.49 0.41 ~ 2.80 0.894 0.13 0.92 ~ 1.54 0.196 Diabetes (No/ Yes) 0.87 0.07 ~ 2.20 0.293 0.20 0.59 ~ 1.30 0.497 CAD (No/ Yes) 0.88 0.13 ~ 3.99 0.698 0.22 0.71 ~ 1.70 0.664 History of Abdominal-Pelvic Surgery (No/ Yes) 0.47 0.43 ~ 2.66 0.896 0.12 0.87 ~ 1.41 0.413 Family History of OC (No/ Yes) 2.28 0.00 ~ 18.17 0.493 0.58 0.10 ~ 0.93 0.038 CA125 (U/mL) 0.00 1.00 ~ 1.00 0.537 0.00 1.00 ~ 1.00 0.349 CA153 (U/mL) 0.00 0.99 ~ 1.00 0.217 0.00 1.00 ~ 1.00 0.004 Albumin (g/L) 0.06 0.76 ~ 0.97 0.011 0.02 0.89 ~ 0.96 <0.001 Serum Total Calcium (mmol/L) 2.11 0.00 ~ 9.07 0.359 0.64 1.64 ~ 19.82 0.006 R0 (Yes/No) 0.47 1.01 ~ 6.46 0.047 0.13 1.43 ~ 2.37 <0.001 HGSC (No/ Yes) 0.18 0.54 ~ 1.07 0.115 0.19 0.50 ~ 1.04 0.080 FIGO Stage (III/IV) 0.15 0.94 ~ 1.67 0.125 0.15 0.84 ~ 1.54 0.394 Abbreviations : OS, Overall Survival; AEOC, Advanced Epithelial Ovarian cancer; SE, Standard Error; 95.0% CI, 95% Confidence Interval; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153; R0, No Macroscopic Residual Tumor After Surgery; HGSC, High Grade Serous Carcinoma; FIGO, International Federation of Gynecology and Obstetrics.
Figure 1 Kaplan-Meier Analysis between Treatment or R level after surgery of OS in AEOC Patients: ( A ) Kaplan-Meier Survival Curves by Initial Treatment Strategy in AEOC Patients; ( B ) Kaplan-Meier Survival Curves by R level after surgery in AEOC Patients; ( C ) Kaplan-Meier Survival Curves by R level after surgery based on PDS Group; ( D ) Kaplan-Meier Survival Curves by R level after surgery based on IDS Group. Image A: Kaplan–Meier Survival Curves by Treatment Strategy. Time (months): 0-125, Survival probability: 0.00-1.00. Curves: PDS, IDS. Log-rank p=0.494. Risk at 0, 25, 50, 75, 100, 125 months: PDS 552, 350, 161, 74, 34, 9; IDS 266, 163, 56, 10, 4, 0. Image B: Curves by R. Time: 0-125, Survival probability: 0.00-1.00. Curves: R0, R1/R2. Log-rank p=4.79e-06. Risk at 0, 25, 50, 75, 100, 125 months: R0 370, 253, 116, 39, 17, 5; R1/R2 448, 260, 101, 45, 21, 4. Image C: Curves by R for PDS Patients. Time: 0-125, Survival probability: 0.00-1.00. Curves: R0, R1/R2. Log-rank p=6.27e-05. Risk at 0, 25, 50, 75, 100, 125 months: R0 220, 150, 74, 32, 13, 5; R1/R2 332, 200, 87, 42, 21, 4. Image D: Curves by R for IDS Patients. Time: 0-120, Survival probability: 0.00-1.00. Curves: R0, R1/R2. Log-rank p=0.00512. Risk at 0, 30, 60, 90, 120 months: R0 150, 86, 20, 5, 1; R1/R2 116, 46, 8, 1, 0. Four line graphs showing Kaplan–Meier survival curves by treatment strategy and R level after surgery. Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; PDS, Primary Debulking Surgery; IDS, Interval Debulking Surgery; R0, No Macroscopic Residual Tumor After Surgery; R1, Macroscopic Residual Tumor ≤1cm After Surgery; R2, Macroscopic Residual Tumor >1cm After Surgery.
Cox Regression Analysis of Prognostic Factors for OS in 818 Patients with AEOC
Abbreviations : OS, Overall Survival; AEOC, Advanced Epithelial Ovarian cancer; SE, Standard Error; 95.0% CI, 95% Confidence Interval; PDS, Primary Debulking Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153; R0, No Macroscopic Residual Tumor After Surgery; HGSC, High Grade Serous Carcinoma; FIGO, International Federation of Gynecology and Obstetrics.
Kaplan-Meier Analysis between Treatment or R level after surgery of OS in AEOC Patients: ( A ) Kaplan-Meier Survival Curves by Initial Treatment Strategy in AEOC Patients; ( B ) Kaplan-Meier Survival Curves by R level after surgery in AEOC Patients; ( C ) Kaplan-Meier Survival Curves by R level after surgery based on PDS Group; ( D ) Kaplan-Meier Survival Curves by R level after surgery based on IDS Group.
The data from our study indicate that neoadjuvant chemotherapy shows no significant efficacy in prolonging AEOC patient survival. However, R0 plays an important role in OS of those patients. Compared to patients undergoing PDS treatment, those undergoing NACT-IDS treatment have a heavier tumor burden and a higher R0 resection rate. Suidan Score is often used to assess satisfactory cytoreductive surgery feasibility in AEOC patients. Next, Validation of the clinical predictive performance of the Suidan score for R0 resectability was performed in the PDS cohort.
Employing the established cut-off value of 3, Suidan score demonstrates sensitivity of 94.09%, specificity of 18.02%, NPV (Negative Predictive Value) of 82.19% and PPV (Positive Predictive Value) of 43.13%. Its limitation is reflected in the overall accuracy of 48.28%, which approximates chance-level performance within PDS cohort. This indicates the imperative to develop and validate more accurate predictive models to guide individualized treatment (PDS or NACT-IDS).
It is difficult to predict whether a patient with AEOC can achieve complete resection. Thus, we establish preoperative models with R0 as the outcome metric for patients with AEOC. Patients are categorized into NACT-IDS group and PDS group based on treatment strategy. Statistically significant differences are observed between the two groups in terms of age, Suidan score, biomarkers, and other indicators ( Table 1 ). This part stratifies the population according to different initial treatment strategies and constructs separate predictive models to progressively screen patients, aiming to enhance the R0 resection rate of surgeries.
An analysis of the PDS training set revealed notable differences between the R0 and non-R0 groups in terms of age, CA125, CA153, albumin, and the Suidan score ( P < 0.05) ( Table 4 ). Diagnostics for Multicollinearity confirmed that these variables are not interrelated ( Supplementary_Table_1 ). Univariate and multivariate logistic regression analyses identified serum CA153 and Suidan score as independent preoperative indicators for achieving an R0 resection ( P < 0.05) ( Table 5 ). Table 4 Baseline Characteristics Comparison Between AEOC Patients with R0 and Non-R0 in the PDS Group (Training and Validation Sets in a 7:3 Ratio) Training Set (n=386) Validation Set (n=166) R0 Group (n=151) Non-R0 Group (n=235) P R0 Group (n=69) Non-R0 Group (n=97) P Age (year) 54.99 (53.37~56.62) 58.00 (56.77~59.21) 0.003 52.86 (55.54~58.21) 56.17 (54.05~58.28) 0.711 Weight (kg) 63.50 (61.81~65.18) 62.33 (60.92~63.74) 0.300 61.20 (59.07~63.32) 62.51 (60.50~64.51) 0.381 Hypertension 0.874 0.911 Yes 39 (25.80%) 59 (25.10%) 14 (20.30%) 19 (19.60%) No 112 (74.20%) 176 (74.90%) 55 (79.70%) 78 (80.40%) Diabetes 0.539 0.813 Yes 12 (7.90%) 23 (9.80%) 5 (7.20%) 8 (8.20%) No 139 (92.10%) 212 (90.20%) 64 (92.80%) 89 (91.80%) History of Abdominal-Pelvic Surgery 0.489 0.728 Yes 52 (34.40%) 73 (31.10%) 21 (30.40%) 32 (33.00%) No 99 (65.60%) 162 (68.90%) 48 (69.60%) 65 (67.00%) Family History of OC 0.550 1.000 Yes 6 (4.00%) 6 (2.60%) 4 (5.80%) 5 (5.20%) No 145 (96.00%) 229 (97.40%) 65 (94.20%) 92 (94.80%) CA125 (U/mL) 471.00 [180.00, 846.00] 885.00 (458.00, 1734.00) <0.001 608.00 [202.77, 1332.00] 988.00 [367.00, 2206.50] 0.005 CA153 (U/mL) 29.10 [16.50, 59.00] 84.59 (33.77, 164.00) <0.001 31.60 [12.21, 54.25] 80.84 [40.97, 155.50] <0.001 Albumin (g/L) 43.01 (42.40~43.61) 41.53 (41.04~42.02) <0.001 42.43 (41.50~43.37) 41.94 (41.22~42.66) 0.410 Serum Total Calcium (mmol/L) 2.32 (2.30~2.34) 2.30 (2.29~2.31) 0.185 2.31 (2.28~2.33) 2.30 (2.28~2.31) 0.611 Suidan Score 1.56 (1.18~1.53) 2.24 (2.06~2.42) <0.001 1.78 (1.46~2.10) 2.32 (2.04~2.60) 0.014 Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; R0, No Macroscopic Residual Tumor After Surgery; PDS, Primary Debulking Surgery; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153.
Table 5 Logistic Regression Analysis for Predicting R0 Resection in the PDS Training Set Variables Univariate Logistic Regression Multivariate Logistic Regression SE 95.0% CI P B SE 95.0% CI P Age (year) 0.01 1.01 ~ 1.06 0.004 0.014 0.01 0.99 ~ 1.04 0.278 Weight (kg) 0.01 0.97 ~ 1.01 0.300 −0.001 0.01 0.98 ~ 1.02 0.925 Hypertension 0.24 0.60 ~ 1.54 0.874 −0.214 0.29 0.46 ~ 1.41 0.452 Diabetes 0.37 0.61 ~ 2.61 0.540 0.389 0.41 0.66 ~ 3.32 0.347 History of Abdominal-Pelvic Surgery 0.22 0.56 ~ 1.33 0.490 0.036 0.25 0.64 ~ 1.69 0.886 Family History of OC 0.59 0.20 ~ 2.00 0.436 −0.203 0.66 0.23 ~ 2.95 0.757 CA125 (U/mL) 0.00 1.00 ~ 1.00 0.002 0.000 0.00 1.00 ~ 1.00 0.676 CA153 (U/mL) 0.00 1.01 ~ 1.01 <0.001 0.008 0.00 1.01 ~ 1.01 <0.001 Albumin (g/L) 0.28 0.85 ~ 0.95 <0.001 −0.051 0.04 0.88 ~ 1.02 0.174 Serum Total Calcium (mmol/L) 0.95 0.04 ~ 1.84 0.187 0.401 1.22 0.14 ~ 16.3 0.742 Suidan Score 0.09 1.46 ~ 2.11 <0.001 0.431 0.11 1.25 ~ 1.90 <0.001 Abbreviations : R0, No Macroscopic Residual Tumor After Surgery; PDS, Primary Debulking Surgery; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA 153, Cancer Antigen 153; SE, Standard Error; B, Coefficient; 95% CI, 95% Confidence Interval.
Baseline Characteristics Comparison Between AEOC Patients with R0 and Non-R0 in the PDS Group (Training and Validation Sets in a 7:3 Ratio)
Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; R0, No Macroscopic Residual Tumor After Surgery; PDS, Primary Debulking Surgery; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153.
Logistic Regression Analysis for Predicting R0 Resection in the PDS Training Set
Abbreviations : R0, No Macroscopic Residual Tumor After Surgery; PDS, Primary Debulking Surgery; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA 153, Cancer Antigen 153; SE, Standard Error; B, Coefficient; 95% CI, 95% Confidence Interval.
A predictive model for preoperative assessment of complete primary tumor excision is formulated using data from the PDS training set. The model equation is Logit( P ) = 0.009 * CA153 + 0.501 * Suidan score - 1.121. The H-L test suggests that the model fit is good ( P = 0.303). In the training cohort, the model records an AUC of 0.763 (95% CI: 0.715 ~ 0.811) ( Figure 2A ), exhibiting a sensitivity of 79.57%, a specificity of 58.28%, a PPV (Positive Predictive Value) of 74.80%, a NPV (Negative Predictive Value) of 64.71%, and an overall accuracy of 71.24%. For the validation cohort, the AUC is 0.705 (95% CI: 0.626 ~ 0.784) ( Figure 2B ). Calibration plots indicate a close match between predicted and observed probabilities in both the training set ( Figure 2C ) and the validation set ( Figure 2D ). The cut-off value is determined to be 0.639. DCA (Decision Curve Analysis) confirms the model’s clinical utility, demonstrating net benefit across a practical threshold range encompassing the training ( Figure 2E ) or validation ( Figure 2F ) set cutoffs.
Figure 2 Evaluation the preoperative prediction model for achieving R0 resection after surgery based on PDS Group: ( A ) ROC curves of the training set; ( B ) ROC curves of the validation set; ( C ) Calibration plot of the training set; ( D ) Calibration plot of the validation set; ( E ) DCA Curve of the training set; ( F ) DCA curve of the validation set. The image A showing a receiver operating characteristic curve. Horizontal axis label: 1 minus Specificity, unit not shown, range 0.00 to 1.00. Vertical axis label: Sensitivity, unit not shown, range 0.00 to 1.00. A diagonal reference line runs from (0.00, 0.00) to (1.00, 1.00). The model curve rises steeply near 1 minus Specificity 0.00 and approaches Sensitivity 1.00 near 1 minus Specificity 1.00. Legend text: Model 0.763(0.715 dash 0.811). The image B showing a receiver operating characteristic curve. Horizontal axis label: 1 minus Specificity, unit not shown, range 0.00 to 1.00. Vertical axis label: Sensitivity, unit not shown, range 0.00 to 1.00. A diagonal reference line runs from (0.00, 0.00) to (1.00, 1.00). The model curve increases stepwise and approaches Sensitivity 1.00 near 1 minus Specificity 1.00. Legend text: Model 0.705(0.626 dash 0.784). The image C showing a calibration plot. Horizontal axis label: Predicted Risk, unit not shown, range 0.0 to 1.0. Vertical axis label: Observed Risk, unit not shown, range 0.0 to 1.0. A diagonal reference line runs from (0.0, 0.0) to (1.0, 1.0). A model line tracks near the diagonal from about Predicted Risk 0.25 and Observed Risk 0.25 through about Predicted Risk 0.75 and Observed Risk 0.80, then levels near Observed Risk about 0.90 to 0.95 as Predicted Risk approaches 1.0. Rug marks appear along the bottom and left edges. The image D showing a calibration plot. Horizontal axis label: Predicted Risk, unit not shown, range 0.0 to 1.0. Vertical axis label: Observed Risk, unit not shown, range 0.0 to 1.0. A diagonal reference line runs from (0.0, 0.0) to (1.0, 1.0). A model line begins around Predicted Risk about 0.25 with Observed Risk about 0.40, fluctuates around Observed Risk about 0.45 to 0.60 between Predicted Risk about 0.40 to 0.70, then rises to Observed Risk about 0.85 to 0.90 near Predicted Risk about 0.90 to 1.0. Rug marks appear along the bottom and left edges. The image E showing a decision curve analysis plot. Horizontal axis label: High Risk Threshold, unit not shown, range 0.0 to 1.0. Vertical axis label: Standardized Net Benefit, unit not shown, range 0.0 to 1.0. A second bottom scale label: Cost:Benefit Ratio, range 1:100 to 100:1 with ticks including 1:4, 2:3, 3:2, 4:1. Three curves are labeled in the legend: Model, All, None. The Model curve starts near Standardized Net Benefit 1.0 at threshold 0.0 and declines toward 0.0 by about threshold 0.9 to 1.0, with small step changes. The All curve declines more steeply and reaches near 0.0 around threshold about 0.6 to 0.7. The None curve lies on Standardized Net Benefit 0.0 across thresholds. The image F showing a decision curve analysis plot. Horizontal axis label: High Risk Threshold, unit not shown, range 0.0 to 1.0. Vertical axis label: Standardized Net Benefit, unit not shown, range 0.0 to 1.0. A second bottom scale label: Cost:Benefit Ratio, range 1:100 to 100:1 with ticks including 1:4, 2:3, 3:2, 4:1. Legend entries: Model, All, None. The Model curve starts near 1.0 at threshold 0.0 and declines toward near 0.0 by about threshold 0.9 to 1.0, with a small upward fluctuation near the far right. The All curve declines steeply and approaches 0.0 around threshold about 0.6. The None curve lies on 0.0 across thresholds. Six plots showing receiver operating characteristic, calibration and decision curve analysis for a model. Abbreviations : ROC, Receiver Operating Characteristic Curve; DCA, Decision Curve Analysis; R0, No Macroscopic Residual Tumor After Surgery.
Evaluation the preoperative prediction model for achieving R0 resection after surgery based on PDS Group: ( A ) ROC curves of the training set; ( B ) ROC curves of the validation set; ( C ) Calibration plot of the training set; ( D ) Calibration plot of the validation set; ( E ) DCA Curve of the training set; ( F ) DCA curve of the validation set.
In conclusion, the model developed based on the PDS group serves as an effective preliminary tool for identifying AEOC patients who are highly likely to undergo complete tumor resection via PDS. This facilitates the preliminary identification of patients who are appropriate candidates for a PDS approach. However, to thoroughly assess which patients might gain greater advantage from the NACT-IDS strategy, an additional predictive model is required. Consequently, the next phase of this research will focus on developing a second model based on the NACT-IDS group, aimed at accurately determining which patients are most likely to achieve R0 via the NACT-IDS treatment pathway.
The NACT-IDS group (n = 266) serves as the training dataset to build a predictive model. Patients are sorted according to their post-surgical resection status, whether it is R0 or non-R0. Significant differences are observed among the groups concerning body weight, CA153, and Suidan score ( Table 6 ). Diagnostics for multicollinearity reveal no issues with collinearity among the risk factors (VIF < 2) ( Supplementary_Table_2 ). Univariate and multivariate logistic regression analyses, which included all factors, indicate that CA153 and Suidan score emerged as independent risk factors ( P < 0.05) ( Table 7 ). The preoperative prediction model for complete resection of the primary lesion, developed based on the PDS group, can be expressed as: Logit( P ) = 1.110 * Suidan score + 0.004*CA153-7.436. Table 6 Baseline Characteristics Comparison Between AEOC Patients with R0 and Non-R0 in the NACT-IDS Group R0 Group (n=150) Non R0 Group (n=116) P Age (year) 59.28 (57.77~60.79) 58.61 (56.91~60.32) 0.563 Weight (kg) 60.14 (58.66~61.62) 57.08 (55.19~58.96) 0.006 NACT 2.96 (2.81~3.11) 2.89 (2.70~3.08) 0.277 Hypertension 0.729 Yes 39 (26.00%) 28 (24.10%) No 111 (74.00%) 88 (75.90%) Diabetes 0.268 Yes 12 (8.00%) 14 (12.10%) No 138 (92.00%) 102 (87.90%) CAD 0.676 Yes 11 (7.30%) 7 (6.00%) No 139 (92.70%) 109 (94.00%) History of Abdominal-Pelvic Surgery 0.875 Yes 44 (29.30%) 33 (28.40%) No 106 (70.70%) 83 (71.60%) Family History of OC 0.550 Yes 6 (4.00%) 2 (1.70%) No 144 (96.00%) 114 (98.30%) CA125 (U/mL) 95.35 [24.35, 669.50] 205.00 [38.55, 848.50] 0.070 CA153 (U/mL) 40.18 [17.45, 125.50] 77.41 [34.05, 169.25] <0.001 Albumin (g/L) 42.62 (41.98~43.26) 42.70 (41.97~43.44) 0.437 Serum Total Calcium (mmol/L) 2.33 (2.31~2.35) 2.33 (2.31~2.35) 0.471 Suidan Score 4.54 (4.26~4.82) 7.91 (7.53~8.28) <0.001 Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; R0, No Macroscopic Residual Tumor After Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen153.
Table 7 Logistic Regression Analysis for Predicting R0 Resection in the NACT-IDS Group Variables Univariate Logistic Regression Multivariate Logistic Regression SE 95.0% CI P B SE 95.0% CI P Age (year) 0.01 0.97 ~ 1.02 0.561 −0.030 0.02 0.93 ~ 1.01 0.183 Weight (kg) 0.01 0.94 ~ 1.00 0.012 −0.015 0.02 0.95 ~ 1.02 0.431 NACT 0.13 0.72 ~ 1.19 0.553 0.009 0.19 0.70 ~ 1.46 0.960 Hypertension 0.29 0.52 ~ 1.59 0.729 −0.223 0.46 0.33 ~ 1.95 0.624 Diabetes 0.42 0.70 ~ 3.56 0.271 0.515 0.70 0.43 ~ 6.59 0.461 CAD 0.50 0.30 ~ 2.16 0.676 −0.356 0.88 0.13 ~ 3.91 0.685 History of Abdominal-Pelvic Surgery 0.27 0.56 ~ 1.64 0.875 0.276 0.42 0.58 ~ 2.99 0.509 Family History of OC 0.30 0.08 ~ 2.13 0.295 −0.766 0.94 0.07 ~ 2.94 0.416 CA125 (U/mL) 0.00 1.00 ~ 1.00 0.372 0.000 0.00 1.00 ~ 1.00 0.101 CA153 (U/mL) 0.00 1.00 ~ 1.01 0.003 0.006 0.00 1.00 ~ 1.01 0.011 Ab (g/L) 0.03 0.95 ~ 1.07 0.873 0.017 0.58 0.91 ~ 1.14 0.768 Serum Total Calcium (mmol/L) 1.20 0.10 ~ 11.4 0.942 −1.429 2.23 0.00 ~ 18.93 0.522 Suidan Score 0.14 2.30 ~ 3.40 <0.001 1.166 0.15 2.38 ~ 4.33 <0.001 Abbreviations : R0, No Macroscopic Residual Tumor After Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153; Ab, Albumin; B, Coefficient; SE, Standard Error; 95.0% CI, 95% Confidence Interval.
Baseline Characteristics Comparison Between AEOC Patients with R0 and Non-R0 in the NACT-IDS Group
Abbreviations : AEOC, Advanced Epithelial Ovarian Cancer; R0, No Macroscopic Residual Tumor After Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen153.
Logistic Regression Analysis for Predicting R0 Resection in the NACT-IDS Group
Abbreviations : R0, No Macroscopic Residual Tumor After Surgery; NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; CAD, Coronary Artery Disease; OC, Ovarian Cancer; CA125, Cancer Antigen 125; CA153, Cancer Antigen 153; Ab, Albumin; B, Coefficient; SE, Standard Error; 95.0% CI, 95% Confidence Interval.
A P -value of 0.156 from the H-L test suggests a well-fitting model. The AUC is 0.911 (95% CI: 0.877 ~ 0.945) ( Figure 3A ). Subsequently, internal validation of the model was performed. The optimism-corrected AUC was 0.909, with a Dxy value of 0.817 and an optimism estimate of 0.0053, indicating excellent discriminative performance and no evidence of substantial overfitting. The optimal cut-off point is determined to be 0.373, yielding a sensitivity of 76.72%, specificity of 86.67%, PPV (Positive Predictive Value) of 81.65%, NPV (Negative Predictive Value) of 82.80%, and an overall accuracy rate of 82.33%. The calibration plot indicates a strong agreement between predicted and observed results, indicating that this multivariate model has excellent discriminative capability, calibration, and predictive performance ( Figure 3B ). The DCA (Decision Curve Analysis) results indicates that prediction model (based on the NACT-IDS Group) has a mark net benefit for predicting an AEOC patient with NACT-IDS can achieve complete resection ( Figure 3C ).
Figure 3 Evaluation the preoperative prediction model for achieving R0 resection after surgery based on NACT-IDS Group: ( A ) ROC curves of the training set; ( B ) Calibration plot of the training set; ( C ) DCA Curve of the training set. Image A: ROC graph with x-axis as 1-Specificity (0-1) and y-axis as Sensitivity (0-1). Diagonal line from (0,0) to (1,1). Curve rises from (0,0) to (0,0.5), then through (0.1,0.75), (0.2,0.88), (0.5,0.98), nearing (1,1). Legend: Model 0.911(0.877-0.945). Image B: Calibration graph with x-axis as Predicted Risk (0-1) and y-axis as Observed Risk (0-1). Diagonal line from (0,0) to (1,1). Curve follows diagonal with deviations at (0.1,0.05), (0.2,0.25), (0.4,0.35), (0.6,0.65), (0.8,0.78), ending near (1,1). Legend: Model. Image C: Decision Curve Analysis graph with x-axis as High Risk Threshold (0-1) and second scale below (1:100 to 100:1). Y-axis is Standardized Net Benefit (0-1). Three curves: Model, All, None. None is horizontal at 0.0. All starts near 1.0 at threshold 0.0, intersects 0.0 line around threshold 0.4. Model starts near 1.0 at threshold 0.0, declines gradually, around 0.8 at 0.2, 0.6 at 0.5, 0.4 at 0.8, nearing 0.1 close to 1.0. Three line graphs showing a receiver operating characteristic curve, a calibration plot and a decision curve. Abbreviations : NACT, Neoadjuvant Chemotherapy; IDS, Interval Debulking Surgery; ROC, Receiver Operating Characteristic Curve; DCA, Decision Curve Analysis; R0, No Macroscopic Residual Tumor After Surgery.
Evaluation the preoperative prediction model for achieving R0 resection after surgery based on NACT-IDS Group: ( A ) ROC curves of the training set; ( B ) Calibration plot of the training set; ( C ) DCA Curve of the training set.
Materials
This study aimed to (1) compare the clinical outcomes of PDS and NACT-IDS in patients with AEOC; (2) identify prognostic factors associated with survival outcomes; (3) assess the clinical utility of the Suidan score and serum biomarkers, particularly CA153, in predicting surgical resectability; and (4) develop predictive models for estimating the probability of achieving R0 resection and supporting individualized treatment selection.
Using the Events Per Variable (EPV) method to calculate the sample size, we set the EPV to 25 with 15 candidate predictor variables. Based on a reported five-year survival rate of 46.20% 14 for the target cohort, the corresponding minimum total sample size was determined to be 818 cases.
This retrospective cohort study analyzed patients with AEOC admitted to Qilu Hospital of Shandong University between January 2014 and December 2023. The inclusion criteria were as follows: (1) complete case and follow-up data; (2) postoperative pathology confirming International Federation of Gynecology and Obstetrics (FIGO) stage III or IV of AEOC; (3) patients presenting for the first time, with no prior relevant treatment before admission; (4) treatment regimen comprising either PDS or NACT-IDS; and (5) surgery performed by the Department of Gynecologic Oncology team at Qilu Hospital of Shandong University, with standardized postoperative treatment and follow-up. The exclusion criteria were: (1) incomplete case or follow-up data; (2) postoperative pathology indicating non-epithelial ovarian cancer, concurrent tumors at other sites, or recurrent/metastatic disease; (3) FIGO stage I–II of AEOC; (4) patients receiving chemotherapy without subsequent debulking surgery; and (5) patients with other severe comorbidities (eg. severe hepatic, renal impairment, autoimmune diseases, thrombotic or hemorrhagic disorders) that led to treatment delays.
Based on these Inclusion and Exclusion criteria, clinical and follow-up data for 818 eligible patients were collected. Data encompassed demographic and clinical characteristics, including age, weight, history of hypertension, diabetes, Coronary Artery Disease, History of abdominal-pelvic surgery, and family history of OC. Pre-treatment laboratory and imaging data, including CA125, CA153, Albumin, Serum total calcium, and a Suidan score, were recorded. Surgical parameters (operation time, performance of bowel resection, blood loss, intraoperative transfusion, and residual disease status), pathological findings, and treatment details (including the number of NACT cycles for the NACT-IDS group) were collected. The neoadjuvant chemotherapy regimen consisted of paclitaxel combined with platinum-based drugs. Follow the recommended dosage in the instruction manual.
The Suidan scoring system was applied according to the updated 2017 criteria. Two experienced radiologists from Qilu Hospital of Shandong University independently re-evaluated all imaging studies. For the PDS group, imaging was assessed prior to surgery, whereas for the NACT-IDS group, imaging was evaluated before initiation of neoadjuvant chemotherapy. The radiologists were blinded to treatment allocation (PDS or NACT-IDS) during scoring to minimize bias. The final Suidan score was calculated as the mean of the two independent assessments to improve reliability.
The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). Follow-up data were obtained from the Gynecology Follow-up Office of Qilu Hospital of Shandong University, including details on postoperative chemotherapy, recurrence, and survival status. All patients were followed until death or the administrative follow-up deadline of December 31, 2024. For this analysis, OS was defined as the time from treatment initiation to death from any cause or the last follow-up. PFS was defined as the time from treatment initiation to confirmed disease progression or the last follow-up; cases with uncontrolled disease from the outset were assigned a PFS of 0. Residual tumor status was classified according to the following criteria: R0 resection indicated No Macroscopic Residual Tumor After Surgery; R1 resection indicated the Macroscopic residual tumor ≤1cm; and R2 resection stated the macroscopic residual tumor >1cm after surgery.
All statistical analyses were conducted using R software (version 4.4.1), SPSS (version 29.0.1), and Excel. Data from 818 patients with AEOC were initially stratified by the achievement of an R0 resection. Quantitative data were tested for normality; normally distributed variables are presented as standard deviation [Mean (95% Confidence Interval, 95% CI)] and compared using independent samples t -tests, while non-normally distributed variables are reported as median and interquartile range [Median (P25, P75)] and compared using the Mann–Whitney U -test. Categorical variables are expressed as frequencies with percentages (%) and compared using the chi-square (χ 2 ) or Fisher’s exact test, as appropriate. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors associated with OS. Kaplan–Meier survival curves comparing treatment groups (PDS vs. NACT-IDS) and residual disease status (R0 vs non‑R0) were generated and assessed using the log‑rank test via the R packages “survival” and “survminer”. Within the PDS cohort (n=552), the Suidan scoring system was validated for predicting R0 resection, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) calculated at a cut-off of 3.
Subsequently, a prediction model for R0 resection was constructed using the PDS population (n=552). The dataset was randomly split into training and validation sets in a 7:3 ratio using Excel’s RAND function. After confirming the absence of multicollinearity among potential predictors, univariate and multivariate logistic regression analyses with stepwise selection were applied to the training set to identify factors associated with R0 resection. The optimal probability cut-off was determined by maximizing the Youden index. Model performance was evaluated by plotting ROC curves and calculating the AUC with 95% confidence intervals for both datasets using (version 4.4.1) R packages “pROC” and “ggplot2”. Internal validation was performed via bootstrap resampling (500 iterations) and calibration curves using the “rms” package, while clinical utility was assessed with decision curve analysis (“rmda” package). An analogous modeling process was applied to the IDS cohort; due to its limited size, the full cohort was used for model development without a separate validation set. Additional internal validation for the IDS model was performed using bootstrap resampling (500 iterations). The optimism-corrected AUC was calculated using Somers’ Dxy with the formula AUC = (Dxy + 1)/2. Model optimism was defined as Index.orig - Index.corrected. A two‑sided P < 0.05 is considered statistically significant.
The Ethics Committee on Scientific Research of Qilu Hospital of Shandong University approved this retrospective study and granted an exemption from the requirement to obtain informed consent from human participants (Approval Number: KYLL-2025-11-066). The clinical trial number is ChiCTR2600116858.
Discussion
This single-center study retrospectively analyzed 818 patients with AEOC treated at Qilu Hospital of Shandong University between January 2014 and December 2023. The baseline characteristics revealed significant differences between patients undergoing PDS and those treated with NACT-IDS, reflecting inherent selection bias present in a real-world setting. 10 The NACT-IDS group was significantly older and had lower body weight ( P < 0.001), suggesting a tendency to allocate NACT to individuals with reduced physiological reserve. 10 Furthermore, comorbidities such as hypertension, diabetes, CAD, previous abdominal-pelvic surgery, and a family history of OC were comparable between the two groups, indicating that systemic medical conditions did not primarily drive treatment selection. 9 These baseline imbalances underscore that patients selected for NACT-IDS represented a clinically more advanced and surgically challenging population, which must be carefully considered when interpreting subsequent comparisons of surgical outcomes and survival 10 ( Table 1 ).
A comparison of survival outcomes was performed between the PDS and NACT-IDS groups within a large cohort of AEOC patients. 15 Although the unadjusted median OS appeared slightly shorter in the NACT-IDS group than in the PDS group ( Table 2 ), multivariable Cox regression 16 ( Table 3 ) and Kaplan–Meier analyses 4 ( Figure 1 ) demonstrated no statistically significant difference in OS between the treatment strategies after adjustment for confounding factors. 15 These findings indicate that NACT-IDS does not consistently prolong OS compared with PDS but rather provides broadly equivalent survival outcomes. 8 This observation aligns with major randomized trials and pooled analyses, such as EORTC 55971 6 and CHORUS. 17 However, inconsistent findings across studies, stemming from variations in patient selection, tumor burden, surgical expertise, and center volume, indicate that survival is determined more by disease biology and surgical completeness than by the choice of initial treatment. 18
Additionally, achieving an R0 resection was the strongest independent prognostic factor for OS, regardless of the treatment strategy of PDS or NACT-IDS. 10 Patients with R0 resection experienced significantly longer survival than those with residual disease, a finding consistent across both groups. 19 The NACT-IDS group exhibited a substantially higher R0 resection rate, along with reduced intraoperative blood loss and fewer bowel resections, supporting the role of NACT in reducing tumor burden to facilitate complete resection ( Table 2 ). 10 These results align with prior studies reporting higher rates of optimal cytoreduction after NACT-IDS, especially in patients with extensive disease. 20 Our findings reinforce the view that IDS do not directly enhance survival; rather, it improves outcomes indirectly by increasing the probability of achieving R0 resection, the principal determinant of long-term prognosis. 21
Although the Suidan score has been widely applied to estimate tumor resectability, our validation analysis identified notable limitations, particularly its low specificity and only modest accuracy in predicting R0. 22 These findings indicate that reliance on the Suidan score alone may be insufficient for individualized preoperative decision-making. 23 To address this limitation, we incorporated serum biomarkers, including CA125 and CA153, into our predictive framework, building upon existing evidence while leveraging our substantially larger sample size to enhance model robustness and stability. 13 Importantly, the predictive model intended to guide initial treatment selection was constructed using the PDS cohort, as the primary clinical question at diagnosis is whether a patient is suitable for upfront debulking surgery. 24 This PDS-based model was designed to identify patients with a high likelihood of achieving R0 resection with primary surgery. 25 In contrast, the IDS cohort represented a biologically and clinically distinct population with a higher baseline tumor burden and more advanced disease. 15 Therefore, a separate IDS-specific model was developed and analyzed to evaluate predictors of R0 resection within this subgroup and to assess the generalizability of the predictive approach. The improved performance observed in the IDS model supports the concept that integrating imaging-based tumor burden scores with serologic biomarkers provides a more comprehensive and adaptable strategy for predicting surgical outcomes across different treatment pathways. 26 , 27
The likelihood of achieving complete cytoreduction was estimated through the development of separate predictive models for patients undergoing PDS and those undergoing NACT-IDS. 28 The Suidan score was strongly associated with treatment allocation and baseline tumor burden, with significantly higher scores observed in patients selected for NACT-IDS, thus underscoring its value as an imaging-based indicator of disease extent and surgical complexity in AEOC. 29 However, when used as a standalone predictor, the Suidan score showed limited discriminatory capacity, particularly due to its low specificity in predicting complete cytoreduction. 30 This aligns with previous studies indicating that while the Suidan score is effective in identifying patients unlikely to achieve optimal upfront cytoreduction, it performs less effectively in predicting those who will achieve an R0 resection. 31 To enhance predictive accuracy, we integrated serum biomarkers, including CA153, into the models. CA153, though traditionally associated with breast cancer, demonstrated significant predictive value in ovarian cancer, correlating with extensive peritoneal involvement and advanced tumor burden. 32 Our findings suggest that CA153 provides additional prognostic and predictive information, complementing the Suidan score and reinforcing its role in a more robust preoperative assessment framework, rather than relying on either marker in isolation. 33
Several observations in our analysis warrant careful interpretation. Certain factors identified as protective in multivariable analysis may reflect unmeasured confounding, treatment heterogeneity, or selection bias inherent to retrospective designs. As this was a single-center study, surgical expertise, perioperative management, and institutional treatment protocols may have influenced outcomes, potentially limiting generalizability. 10 The absence of propensity score matching (PSM) may have resulted in residual confounding; therefore, the observed associations should be interpreted with caution. Additionally, only 3.50% of patients in our cohort reported a family history of ovarian cancer (<5.00%), making BRCA/ homologous recombination deficiency (HRD) testing a secondary consideration in this study. Regional disparities in healthcare access across China resulted in inconsistent uptake of maintenance therapies. 34 Therefore, maintenance therapies, including PARP inhibitors and bevacizumab, were not included in the prognostic analysis. External validation of predictive models, along with the roles of protective family history, BRCA/HRD status, and maintenance therapies warrant further investigation in future studies.
Despite these limitations, the present study provides clinically meaningful insights into treatment selection and surgical planning for AEOC. PFS and OS did not differ significantly between patients undergoing PDS and those undergoing IDS, as confirmed by Kaplan-Meier and Cox regression analyses. 9 Although the baseline characteristics suggested that OS appeared longer in the PDS group, this apparent advantage is likely due to imbalances in baseline features such as age, performance status, tumor burden, and other confounding factors. 15 Cox regression analysis, by adjusting for these variables, provides a more accurate assessment of the independent effect of the surgical approach. Kaplan–Meier analysis may not fully capture OS trends due to early event clustering, small cohort sizes, or infrequent endpoint occurrences. 35 , 36 Additionally, differences in surgical quality, including R0 resection rates and subsequent treatments, such as chemotherapy regimens or crossover therapy, may further dilute the effect of the surgical approach on OS. 37 Therefore, interpretation of survival outcomes should prioritize Cox regression results while considering Kaplan–Meier curve morphology, surgical quality indicators, and long-term survival data. Importantly, precise preoperative evaluation is essential to determine whether patients should undergo PDS or NACT-IDS, with the likelihood of achieving R0 resection serving as a critical outcome indicator. 9 , 38
Another key contribution of this study is the development of treatment-specific predictive models to support individualized surgical decision-making. Models developed from the PDS population can be used to assess whether AEOC patients can achieve R0 resection through primary surgery, whereas models developed using the IDS population can evaluate whether patients can achieve R0 resection following the NACT-IDS approach. These tools may assist clinicians in identifying patients most likely to benefit from PDS or NACT-IDS and contribute to more individualized and evidence-based treatment planning in AEOC.