Primary Cytoreductive Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: the Primary Cytoreductive Surgery is Better Than Neoadjuvant Chemotherapy in Platinum-resistant Patients

Primary Cytoreductive Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: the Primary Cytoreductive Surgery is Better Than Neoadjuvant Chemotherapy in Platinum-resistant Patients | 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 Primary Cytoreductive Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: the Primary Cytoreductive Surgery is Better Than Neoadjuvant Chemotherapy in Platinum-resistant Patients basak ozge kayan, tugan bese, hande turna, sennur ilvan, sukru cebi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4587958/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : We investigated the outcome of neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery and primary cytoreductive surgery (PCS) in patients with platinum-sensitive or resistant advanced epithelial ovarian cancer. Materials and methods: The inclusion criteria fit 298 patients who underwent primary cytoreductive surgery (PCS group n=158) or neoadjuvant chemotherapy (NACT group n=140). Differences in characteristic features, chemotherapy responses, and prognosis were compared. Results: Although the median DFS was similar between the two groups, the median OS was significantly longer in the PCS (p=0.025). There was no survival advantage between the two groups regarding OS in platinum-sensitive patients. However, OS was significantly longer in platinum-resistant patients who underwent PCS (p=0.011). The rate of complete cytoreduction (R=0) was 47.5% in the PCS and 67.1% in the NACT group (p=0.001). Although DFS and OS advantages were observed in the PCS group in R=0 patients with a residual tumor, no significant difference was noticed between the two groups. The two groups had no OS advantage when platinum-sensitive patients were assessed for residual tumor. Meanwhile, in platinum-resistant patients, R=0 provided OS advantage in the PCS group (p=0.008). However, no significant difference was observed if there was any residual tumor (p=0.091). Conclusion: OS was significantly longer in the PCS group. Survival is better in platinum-resistant patients if no residual tumor exists after PCS. There was no difference in OS between the PCS and NACT groups in platinum-sensitive patients, regardless of residual tumor. Specific methods and markers are needed before initial treatment in epithelial ovarian cancer. primary cytoreduction interval cytoreduction platinum-resistance platinum-sensitive residual tumor Figures Figure 1 Figure 2 Figure 3 Take-home message Platinum sensitivity and residual tumor are the most important prognostic factors in advanced epithelial ovarian cancer. If patients are platinum-sensitive, both NACT and PCS have similar survival rates, and PCS with no residual tumor increases the success of the treatment in platinum-resistant patients. INTRODUCTION Ovarian cancer is the third most common gynecological malignancy in women worldwide ( 1 ). As it does not cause early symptoms, most of the patients are diagnosed at an advanced stage. Therefore, 5-year life expectancy is lower than 50% ( 2 ). The standard treatment for advanced epithelial ovarian cancer is primary cytoreductive surgery (PCS), followed by platinum-based adjuvant chemotherapy. No visible residual tumor after surgery is one of the most important prognostic factors for survival ( 3 – 5 ). Retrospective studies revealed that optimal cytoreduction (R < 1cm) could be achieved in 48–72% of cases with advanced ovarian cancer with PCS, while complete cytoreduction (R = 0) rate was approximately 29–35% ( 6 – 10 ). NACT followed by interval cytoreductive surgery (ICS) is preferred as an alternative treatment for patients in whom optimal cytoreduction is assumed not to be achieved due to tumor spread and comorbidity factors. However, still the choice of first-line treatment method in advanced epithelial ovarian cancer has not been clarified. Recent prospective, randomized controlled studies demonstrated that the rate of optimal cytoreduction in NACT is better than in PCS. Whereas, DFS and OS were similar between the PCS and NACT groups ( 11 – 13 ). Several retrospective studies reported that OS was longer in patients with stage IV ovarian cancer who underwent NACT than PCS ( 14 , 15 ). There is no method to determine platinum sensibility before ovarian cancer treatment. Although some studies show that at the first relapse, the platinum resistance is higher in the NACT than in the PCS group ( 16 – 18 ), there are also studies that platinum resistance is similar in the first relapse but higher in the second relapse in the NACT group ( 19 , 20 ). The aim of this study is to investigate the outcome of neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery and primary cytoreductive surgery (PCS) in patients with platinum-sensitive or resistant advanced epithelial ovarian cancer. MATERIALS AND METHODS Study design and population This observational retrospective study was conducted at Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Obstetrics and Gynecology, Gynecological Oncology Division. The study protocol was approved by the ethical committee (Study number 12.04.2022–359584). The study group consisted of patients who were followed up in our clinic between December 1993 and November 2020, who underwent PCS and then received chemotherapy or received NACT followed by interval cytoreductive surgery. International Federation of Gynecology and Obstetrics (FIGO) stages III-IV epithelial ovarian carcinomas, older than 18, chemotherapy and radiotherapy naive eligible 298 patients’ files were analyzed retrospectively. One hundred fifty-eight patients were in PCS followed by adjuvant chemotherapy (PCS group), and 140 were in NACT followed by ICS (NACT group). Of the NACT group, 26.4% received three and 34.3% four cycles of chemotherapy. Patients (39.3%) who were considered to have an inadequate response to 3–4 cycles of chemotherapy by high serum cancer antigene − 125 (CA-125) level and radiological examination findings received six cycles of NACT. The exclusion criteria of the study were pregnancy, lactation, non-epithelial ovarian malignancies, borderline ovarian tumors, another known or concurrent malignancy, previous history of chemotherapy due to any kind of tumor, and abdominal or pelvic radiotherapy. In our clinic, the cancer diagnosis was made before NACT, with a tru-cut biopsy of the tumor mass or cytology results of thoracentesis/paracentesis. Eligibility criteria of NACT were: Eastern Cooperative Oncology Group (ECOG) performance status 3–4, multiple intraparenchymal liver metastases, pulmonary parenchymal metastases, bulky lymphadenopathy (LAP) at the root of the superior mesenteric artery, extensive implants in the small intestine mesentery, metastasis in the porta hepatis and diffuse peritonitis carcinomatosa findings in radiological findings with massive abdominal acid and serum CA-125 > 1000 U/ml. Data collection Hysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritonectomy, pelvic and/or paraaortic lymphadenectomy, and if necessary organ resections for cytoreduction, were performed. The definition of complete cytoreduction is no residual tumor after surgery, optimal cytoreduction is residual tumor less than 1 cm, and suboptimal cytoreduction is residual tumor more than 1 cm. Patients were followed every 3 months for 2 years, every 6 months for 2 to 5 years, and annually after 5 years with gynecological examination and serum CA-125 level. Radiological scans were performed annually or whenever needed. The treatment decision was not made only due to high serum CA-125. The disease's relapse or progression was determined by clinical or radiological findings. Disease-free survival (DFS) was defined as the time between the last dose of platinum-based chemotherapy and recurrence. Overall survival (OS) was described as the period to the date of death or last follow-up. Those that persisted or recurred within the first 6 months after completing the initial treatment were included in the platinum-resistant group, and those that relapsed after 6 months and who have no recurrence were included in the platinum-sensitive group. Statsitical analysis Collected data were evaluated by IBM SPSS Version 21. The Chi-square and Student's t-test were used to determine the relationship between variables. DFS and OS were estimated using the Kaplan-Meier method and log-rank test. Hazard ratio with 95% confidence interval (CI) was determined for each variable. Cox regression analysis was used to determine prognostic factors on survival. The p-significance value was taken as < 0.05. RESULTS The median follow-up period was 31 months for all patients included in the study. Disease persistence or recurrence was detected in 84.2% (n = 251) of all cases, and 62.8% (n = 187) of patients died. The distribution of the characteristics of the patients in the PCS and NACT groups was not homogeneous. Age, initial serum CA-125 levels, serous histological type, and stage IV disease rate were significantly higher in the NACT group. While the rate of no residual tumor (R = 0) was 47.5% in the PCS group, it was 67.1% in the NACT group (p = 0.001). There was no significant difference between menopausal status, BMI, histological grade, and platinum sensibility (Table 1 ). Table 1. COMPARISON OF DEMOGRAPHIC CHARACTERISTICS OF PCS AND NACT GROUPS CHARACTERISTICS PCS (n=158) NACT (n=140) p-value Age (median -range) 53.1 (28-85) 61.2 (26-86) 0,000 CA-125 (u/ml) (median -range) 448 (16-13.165) 1009 (11-30.119) 0,003 CA-125 - n(%) <1000 u/ml ≥1000 u/ml 99 (74.4) 34 (25.6) 65 (47.4) 72 (52.6) 0,000 BMI (median - range) 29.2 (17-45) 29.8 (18-53) 0,492 MENOPAUSE - n(%) premenopause postmenopause 48 (30.4) 110 (69.4) 29 (20.7) 111 (79.3) 0,057 HISTOLOGICAL GRADE - n(%) low grade high grade 10 (6.3) 148 (93.7) 6 (4.2) 134 (95.8) 0,601 HISTOLOGICAL TYPE - n(%) serous others 140 (88.6) 18 (11.4) 138 (98.6) 2 (1.4) 0,001 STAGE - n(%) III IV 150 (94.9) 8 (5.1) 116 (82.9) 24 (17.1) 0,002 PLATINUM SENSIBILITY- n(%) Platinum-sensitive Platinum-resistant 90 (59.6) 61 (40.4) 72 (52.6) 65 (47.4) 0,229 RESIDUAL DISEASE - n(%) R< 1 cm R≥ 1 cm 108 (68.4) 50 (31.6) 126 (90) 14 (10) 0,000 RESIDUAL DISEASE - n(%) R=0 cm R + cm 75 (47.5) 83 (52.5) 94 (67.1) 46 (32.9) 0,001 The median DFS in all cases was 8 months in the PCS group and 7 months in the NACT group, and there was no difference between the groups (p = 0.176; HR: 1.171, 95.0% CI[0.913– 1.503]). DFS was not evaluated in platinum-resistant cases. In platinum-sensitive patients, there was no significant difference between these two groups (p = 0.478; HR: 1.134 95.0% CI[0.793– 1.620]). The median OS was 39 months in the PCS group and 26 months in the NACT group, and OS was significantly longer in the PCS than in the NACT group (p = 0.016; HR: 1.427, 95.0% CI[1.063.– 1.914]). In platinum-sensitive cases, there was no OS advantage was observed between the groups (p = 0.204; HR: 0.209, 95.0% CI[0.845– 2.157]). However, in platinum-resistant cases, OS was 21 months in the PCS and 13 months in the NACT group, and OS was significantly longer in the platinum-resistant PCS group (p = 0.011; HR: 1.654, 95.0% CI[1.110– 2.465]), (Fig. 1 A-B). When patients with no residual tumor (R = 0) in NACT and PCS groups were compared, DFS and OS were significantly longer in the PCS (DFS p = 0.009; HR: 1.548, 95.0% CI [1.097– 2.185] and OS p = 0.000; HR: 2.110, 95.0% CI[1.371– 3.248]). If there was any residual tumor, there was no significant difference between the two groups (DFS, p = 0.547; HR: 1.099, 95.0% CI [0.753– 1.604] and OS, p = 0.198; HR:1.318, 95.0% CI[0.861– 2.017]) (Fig. 2 A-B). In terms of platinum sensibility, sub-group analysis revealed no OS advantage between PCS and NACT groups in platinum-sensitive cases with or without residual tumor. In platinum-resistant R = 0 cases, the median OS was 41.5 months in the PCS and 16 months in the NACT group, significantly longer in the PCS (OS, p = 0.008; HR: 3.303, 95.0% CI [1.295– 8.430]). Whereas, in platinum-resistant R + patients, no statistically significant difference was found between the groups (OS, p = 0.091; HR: 1.515, 95.0% CI[0.927– 2.475]),(Fig. 3 A-B). The characteristics of the patients such as age, BMI, serum CA-125 level, menopausal status, and histological grade were evaluated with Kaplan Meier log-rank χ2 analysis, and no significant difference was found in DFS and OS (p > 0.05) (Table 2 ). Table 2. KAPLAN MEIER SURVIVAL ANALYSIS OF CHARACTERISTICS DFS OS MEAN ( month) MEDIAN month 5 years p-value MEAN (month) MEDIAN month 5 years p-value TREATMENT PCS (n=158) NACT (n=140) 17.5 14 8 7 13.9% 10.9% 0.156 45.7 31.5 39 26 40.5% 31.4% 0.025 RESIDUAL DISEASE R=0 (n=169) R +(n=129) 21.2 8.9 14 0 16.2% 8% 0.000 45.6 30.4 37 21 46.3% 23.6% 0.000 PLATINUM SENSIBILITY Platinum-sensitive (n=162) Platinum-resistant (n=126) 28.3 1 19 0 21,9% 0% 0.000 52.9 24 45 17.5 56.3% 12% 0.000 AGE ≤ 58 (n=144) > 58 (n=154) 15.8 15.9 7 7 9.5% 15.7% 0.800 42.8 35.5 38.5 28.5 42.4% 30.1% 0.355 BMI < 30 (n=152) ≥ 30 (n=146) 16.7 15 7 7.5 14.2% 10.9% 0,747 37.1 41.1 28 34.5 34.6% 37.9% 0.942 MENOPAUSE Pre (n=77) Post (n=221) 12.7 17 6 7 7.7% 14.5% 0.054 38.3 39.3 33 31 40.3% 35% 0.850 CA-125 u/ml <1000(n=164) ≥1000(n=106) 15.4 13.1 7.5 5 13.7% 8.1% 0.171 35 35.4 30 26 34.1% 36.3% 0.668 HISTOLOGICAL GRADE Low (n=16) High (n=282) 17.4 15.8 6.5 7 12.5% 12.4% 0.451 52.4 38.3 39.5 31 41.3% 36% 0.638 STAGE III (n=266) IV (n=32) 16.6 9.4 7 1 12.9% 10.7% 0.089 40.8 24 32 21 37.2% 27.7% 0.161 HISTOLOGICAL TYPE Serous (n=278) Others (n=20) 16.5 7.4 7 0 12.8% 0% 0.162 40.3 21.8 32 19 37.2% 0% 0.050 When the parameters were evaluated by multivariate Cox Regression analysis, platinum-sensitive disease (HR: 4.138, 95% CI [2.982–5.743]; p = 0.000), PCS as the first treatment (HR: 1.612, 95% CI [1.195–2.176]; p. =0.002), and no residual tumor after surgery (HR: 1.430, 95% CI [1.040–1.966]; p = 0.027) were determined as the most significant independent prognostic factors. DISCUSSION Summary of Main Results Standard treatment in advanced ovarian cancer is PCS, followed by adjuvant chemotherapy. In the preoperative evaluation of patients with suspected stage III-IV epithelial ovarian cancer, laparoscopic, radiological, and biochemical findings can be combined with scoring systems for surgery suitability ( 21 , 22 ). Wright et al. recommended that NACT was preferred only in patients with a high perioperative risk profile and a low chance of achieving optimal cytoreduction in PCS ( 23 ). However, there are also studies indicating that 5–12% of the patients have a complete response after NACT, and the prognosis in these patients is excellent ( 24 , 25 ). In our study, no significant difference was observed in DFS between the PCS and NACT groups. Nevertheless, similar to most retrospective studies, OS was significantly longer in the PCS group. Considering those without residual tumor after surgery, survival was better in the PCS group than in the NACT group. There was no survival advantage between NACT vs PCS groups in platinum-sensitive patients. This result eliminates the importance of PCS as a first treatment option in platinum-sensitive cases. Since the surgical complication rate is generally low in the NACT, applying NACT as a first-line treatment can be a good option if the patient is platinum-sensitive. Even whether the patient is chemo-sensitive or –resistant is not known initially. Results in the Context of Published Literature Most retrospective studies revealed that PCS provides DFS and OS advantages over NACT. In the study by Rauh-Hain et al., which searched the US National Cancer Database and selected 2935 similar cases for both groups, the median OS was found to be 37.3 months in the PCS group and 32.1 months in the NACT group (p < 0.001) ( 26 ). Lyons et al. published a retrospective analysis of approximately 37.000 patients in the National Cancer Database, and the OS was longer in the PCS group ( 7 ). In another retrospective cohort study conducted by Matsuo et al., queried by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER), ovarian cancer mortality (3-year cumulative incidence) was 41.9% in the PCS and 47.5% in the NACT group (p < 0.001) ( 8 ). Gao et al. found a difference of 5.5 months in DFS and 15.5 months in OS between two groups in favor of the PCS. However, no statistically significant difference was observed ( 9 ). In our study, the decision of PCS or NACT was determined according to the initial clinical and radiological findings. In the NACT group, tumor load was rather extensive, patients were old, initial serum CA-125 levels were high, and the number of patients with stage IV and ECOG performance scores of 3–4 with comorbidities were much higher than in the PCS group. The distribution of patient characteristics between the two groups was non-homogeneous; that was the crucial bias in our study. Prospective randomized trials have also been administered for NACT as an alternative therapy in advanced ovarian cancer. The first was completed in 2010 by the European Gynecological Cancer Research and Treatment Group (EORTC-GCG 55791). Although complete tumor resection was 19.4% in PCS and 51.2% in NACT, there was no significant difference in DFS and OS. No residue tumor was the most important independent prognostic factor ( 11 ). In another randomized controlled phase 3 trial, CHORUS was published in 2015, the complete cytoreduction rate was 17% in PCS and 39% in NACT, and there was no statistically significant difference in DFS and OS. It has been suggested that NACT was a good alternative treatment, especially in cases with low-performance scores, due to its lower morbidity and mortality rates ( 12 ). The prospective, randomized, controlled phase 3 study SCORPION was emitted in 2020. The complete cytoreduction rate was 47.6% in PCS and 77% in the NACT group, and there was no significant difference between DFS and OS. However, postoperative death and major complication rates were significantly higher in the PCS group than in the NACT group ( 13 ). Also, in the prospective randomized study (JCOG 0602) of the Japanese Gynecological Oncology Group issued in 2020, complete resection was found to be 12% in the PCS and 64% in the NACT group. The median DFS was 15.1 months in the PCS, 16.4 months in the NACT group, and the median OS was 49 months in the PCS and 44.3 months in the NACT group. The result of this study was a little different compared to other prospective randomized studies, and the authors concluded that a survival noninferiority of NACT was not confirmed in their study compared with PCS. NACT might not be replaced every time for PCS ( 27 ). In retrospective studies, survival was better in the PCS group; randomized and prospective studies revealed that survival outcomes in the NACT group are non-inferior to PCS. The results of incoming studies (TRUST (Clinical Trial NCT02828618) and SOC-2 (Clinical Trial NCT02859038)) have not been published yet. No residual tumor after surgery is an important prognostic factor for survival. Recent studies have shown that ICS after NACT provides a high complete/optimal cytoreduction rate and less surgical morbidity ( 3 – 6 , 27 , 28 ). In our study, the rates of no residual tumor (R = 0) between the two groups favored the NACT group, similar to randomized controlled studies. DFS and OS were longer in R = 0 patients in the PCS group. DFS and OS were similar to the NACT group in the PCS group with residual tumors. Although there was no statistically significant result in two different retrospective studies, the tendency of OS advantage was found in the PCS group with no residual tumor ( 7 , 9 ). Platinum sensitivity is as important as no residual tumor in advanced ovarian cancer. However, there is still no marker that can be used in practice to predict platinum sensibility. On the other hand, ATP-dependent transporter gene (ABCB1), ATP binding cassette G2 (ABCG2) overexpression with Wnt/b-catenin pathway, astrocyte elevated gene-1 (AEG-1) expression, PI3K/Akt/mTOR pathway activation and TP53 K351N, PTEN, BRCA1/2, KRAS, BRAF, β-catenin gene mutations and chromosome instability are associated with platinum resistance ( 30 – 33 , 34 ). As most patients have both platinum-sensitive and platinum-resistant cells at the first diagnosis, approximately 80% of newly diagnosed epithelial ovarian cancer cases respond to first-line platinum-based chemotherapy. Despite this, approximately 70% of patients relapse, and most turn to the platinum-resistant phase ( 21 ). In our study, the rate of platinum resistance was 40.4% in the PCS and 47.4% in the NACT group. Large tumors are poorly vascularized, and they are hypoxic and necrotic. The higher the tumor burden at the start of treatment, the greater the probability of tumor mutation and platinum resistance. Reducing the tumor burden with PCS minimizes the number of cells that can transform into platinum-resistant phenotypes. If the treatment is started with NACT, tumor cells have more probability of developing a platinum-resistant phase. Due to this condition, NACT is suggested not to be as effective as desired ( 9 , 29 ). According to Liu et al., most studies are limited because they are retrospective and biased in patient selection criteria, so it is difficult to conclude that NACT increases the likelihood of platinum resistance. However, the possibility of NACT causing more platinum resistance should not be ignored ( 35 ) Strengths and Weaknesses Our weaknesses are the non-homogeneous patient characteristics between the two groups and the retrospective study. Our strengths are the sufficient follow-up period and the number of patient groups. Implications for Practice and Future Research We could not find a study in the literature that PCS provides a survival advantage in chemotherapy-resistant patients. New studies are needed to compare our results. In addition, a method should be developed to determine the disease's sensitivity to chemotherapy. CONCLUSION We revealed that if the patient is platinum-sensitive, PCS as a first-line treatment was not essential because NACT could be used effectively. On the other hand, in platinum-resistant with R = 0 cases, the PCS as the first treatment provides a better survival advantage. The problem is that we make the initial treatment selection based on clinical findings, and we cannot detect platinum sensibility before starting treatment. Detection of a specific method that determines platinum sensibility is a critical issue in ovarian cancer. If platinum resistance can be assigned before treatment, it would be more rational to prefer PCS. Declarations FUNDING The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. DATA AVAILABILITY The datasets generated in this study are available from the corresponding author upon request. Competing interests : The authors have no relevant financial or non- financial interests to disclose. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the ethical committee (Study number 12.04.2022 - 359584). Informed consent statement: Informed consent was waived due to the retrospective study design. Patient data were anonymized at the time of collection and patient identification is not possible. CONFLICT OF INTEREST The authors have no conflicts of interest to declare. AUTHOR CONTRIBUTION BOK and TB have made significant contributions to the design and acquisition, analysis, and interpretation of data. All authors participated in the drafting and revision of the article, gave consent for publication of the article, and confirmed the accuracy of the data and analysis and the adequacy of the protocol of the article. References Globocan 2020 The Global Cancer Observatory - All Rights Reserved, March, 2021. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf De Angelis R et al (2014) Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol 15(1):23–34 Winter WE 3rd et al (2007) Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25(24): 3621–3627 Winter WE 3rd et al (2008) Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 26(1): 83–89 du Bois A et al (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux pour les Etudes des cancers de l'Ovaire (GINECO). Cancer 115(6):1234–1244 May T et al (2017) A comparison of survival outcomes in advanced serous ovarian Cancer patients treated with primary Debulking surgery versus neoadjuvant chemotherapy. Int J Gynecol Cancer 27(4):668–674 Lyons YA et al (2020) Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy. Int J Gynecol Cancer 30(6):845–852 Matsuo K et al (2021) Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer. Gynecol Oncol 160(1):32–39 Gao Y et al (2019) Evaluating the benefits of neoadjuvant chemotherapy for advanced epithelial ovarian cancer: a retrospective study. J. Ovarian Res 12(1):85 Tseng JH et al (2018) Continuous improvement in primary Debulking surgery for advanced ovarian cancer: Do increased complete gross resection rates independently lead to increased progression-free and overall survival? Gynecol Oncol 151(1): 24-31 Vergote I et al (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363(10):943–953 Kehoe S et al (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. The Lancet 386(9990):249–257 Fagotti A et al (2020) Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int J Gynecol Cancer 30(11):1657–1664 Tajik P et al (2018) The FIGO stage IVA versus IVB of ovarian Cancer: prognostic value and predictive value for neoadjuvant chemotherapy. Int J Gynecol Cancer 28(3):453–458 Hou JY et al (2007) Neoadjuvant chemotherapy lessens surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease. Gynecol Oncol 105(1):211–217 Luo Y et al (2016) Effect of neoadjuvant chemotherapy on platinum resistance in stage IIIC and IV epithelial ovarian cancer. Medicine (Baltimore) 95(36):e4797 Makar AP et al (2016) Advanced ovarian Cancer: primary or interval Debulking? Five categories of patients in view of the results of randomized trials and tumor biology: primary Debulking surgery and interval Debulking surgery for advanced ovarian Cancer. Oncologist 21(6):745–754 Petrillo M et al (2013) Timing and pattern of recurrence in ovarian cancer patients with high tumor dissemination treated with primary debulking surgery versus neoadjuvant chemotherapy. Ann Surg Oncol 20(12):3955–3960 Rauh-Hain JA et al (2013) Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma. Gynecol Oncol 129(1):63–68 da Costa AA et al (2015) Neoadjuvant chemotherapy followed by interval Debulking surgery and the risk of platinum resistance in epithelial ovarian Cancer. Ann Surg Oncol 22(3):S971–978 Fagotti A et al (2008) Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am. J. Obstet. Gynecol 199(6):642.e1–642.e6 Qin L et al (2018) Clinical study of a CT evaluation model combined with serum CA125 in predicting the treatment of newly diagnosed advanced epithelial ovarian cancer. J Ovarian Res 11(1):49 Wright AA et al (2016) Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. Gynecol Oncol 143(1):3-15 Michaan N et al (2018) Prognostic value of pathologic chemotherapy response score in patients with ovarian Cancer after neoadjuvant chemotherapy. Int J Gynecol Cancer 28(9):1676–1682 Petrillo M et al (2014) Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer. Am J Obstet Gynecol 211(6):632.e1–e8 Rauh-Hain JA et al (2017) Neoadjuvant Chemotherapy Compared with Primary Cytoreductive Surgery in Women with Epithelial Ovarian Cancer: Analysis of the National Cancer Database. JAMA Oncol 3(1):76–82 Onda T et al (2020) Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers in phase III randomised trial. Eur J Cancer 130:114-125 Xiao Y et al (2018) Platinum-based neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma International Federation of Gynecology and Obstetrics Stages IIIc and IV: a systematic review and meta-analysis. Gynecol Obstet Investig 83(3):209–219 Leary A et al (2016) Primary surgery or neoadjuvant chemotherapy in advanced ovarian cancer: the debate continues. Am Soc Clin Oncol Educ Book 35:153–162 Chau W et al (2013) c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/beta-catenin-ATP- binding cassette G2 signaling. Oncogene 32(22):2767–2781 Park JT et al (2010) Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am. J. Pathol 177(3):1087–1094 Zhang GN et al (2014) TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer. Gynecol Oncol 132(13):752–757 Patch AM et al (2015) Whole-genome characterization of chemoresistant ovarian cancer. Nature 521(7553):489–494 Takaya H et al (2020) Intratumor heterogeneity and homologous recombination deficiency of high-grade serous ovarian cancer are associated with prognosis and molecular subtype and change in treatment course. Gynecol Oncol 156(2):415–422 Liu J, Jiao X, Gao Q (2020) Neoadjuvant chemotherapy-related platinum resistance in ovarian cancer. Drug Discovery Today 25(7):1232-1238 Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4587958","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321018422,"identity":"432ba557-856d-4bf5-8a77-273506d27e9e","order_by":0,"name":"basak ozge kayan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYBACAyBmbACxeMB8GwYGCRK1pJGu5TBhLebsxx9+nFFRZ9fPc/iZxM8d5xP7ZzcffMBQYxONS4tlT46x5IYzbMkze9vMJHvP3E6ccedYsgHDsbTcBlwOO5DDIPmwjSfZ4DyDmQRv2+3Ehhs5ZhKMDYdxazn//PHPh20Syfbn2b9J/m07lzifoJYbCWaSG9sM7Ax4e8ykedsOJG4gpMVyxhszyxlnEhIkzpwptpZtSzbeeCMt2SABj1/M+dMf3+ypqLPn70nfePNtm53svBvJBx98qLHBqQUGEoEKWEAx4ghWmUBAOQjYAzHzByhjFIyCUTAKRgEKAADRj2IlfeokwwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-0699-0482","institution":"Istanbul Bilim Universitesi","correspondingAuthor":true,"prefix":"","firstName":"basak","middleName":"ozge","lastName":"kayan","suffix":""},{"id":321018423,"identity":"ee04b314-9e0b-40d6-a4eb-e51863d3fb33","order_by":1,"name":"tugan bese","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"tugan","middleName":"","lastName":"bese","suffix":""},{"id":321018424,"identity":"0c75b607-3f6d-49a8-adf8-a161468df576","order_by":2,"name":"hande turna","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"hande","middleName":"","lastName":"turna","suffix":""},{"id":321018425,"identity":"10061b66-4297-4886-805c-2283d24141a6","order_by":3,"name":"sennur ilvan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"sennur","middleName":"","lastName":"ilvan","suffix":""},{"id":321018426,"identity":"de779b19-c69d-4937-b478-018fea7f192d","order_by":4,"name":"sukru cebi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"sukru","middleName":"","lastName":"cebi","suffix":""},{"id":321018427,"identity":"0813e160-62af-4b8a-9f27-0438b59468cc","order_by":5,"name":"serdar acikgoz","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"serdar","middleName":"","lastName":"acikgoz","suffix":""},{"id":321018428,"identity":"23ee8fe6-1e96-43dd-83e5-0a251d11727a","order_by":6,"name":"yeliz aykanat","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"yeliz","middleName":"","lastName":"aykanat","suffix":""},{"id":321018429,"identity":"12c6d373-a388-40fc-af39-194fae60b900","order_by":7,"name":"melike makul","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"melike","middleName":"","lastName":"makul","suffix":""},{"id":321018430,"identity":"5c6ffb10-b95b-4a2f-887a-95bd74b240c2","order_by":8,"name":"fuat demirkiran","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"fuat","middleName":"","lastName":"demirkiran","suffix":""}],"badges":[],"createdAt":"2024-06-15 23:45:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4587958/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4587958/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60944677,"identity":"d2c5bbe8-c91e-4b97-a2aa-6b66bad9c296","added_by":"auto","created_at":"2024-07-23 22:14:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106837,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eA: OS for all patients , PCS vs NACT. B: OS for platinium resistant patients, PCS vs NACT.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4587958/v1/bb8ccef993a1fdca4aed4c6b.png"},{"id":60944675,"identity":"c2046a50-b096-47c1-aa12-e49872d9410f","added_by":"auto","created_at":"2024-07-23 22:14:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":131816,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eA: DFS in terms of residual tumor , PCS vs NACT. B: OS in terms of residual tumor, PCS vs NACT.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4587958/v1/1f70a01e3133d5d92d09312e.png"},{"id":60944676,"identity":"82f4b6a6-97ac-4e8e-9ff9-83bcadda9735","added_by":"auto","created_at":"2024-07-23 22:14:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":104421,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eA: OS in terms of platinium resistant and R=0 patients , PCS vs NACT. B: OS in terms of platinium resistant and R + patients , PCS vs NACT\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4587958/v1/36defdbbcbd256dc5aa90fe4.png"},{"id":63045583,"identity":"93c24785-877e-49a1-a106-f8f8be934eda","added_by":"auto","created_at":"2024-08-22 12:38:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1035601,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4587958/v1/da3ea550-db8a-4acd-b38e-2242aa42293b.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003ePrimary Cytoreductive Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: the Primary Cytoreductive Surgery is Better Than Neoadjuvant Chemotherapy in Platinum-resistant Patients\u003c/p\u003e","fulltext":[{"header":"Take-home message","content":"\u003cp\u003ePlatinum sensitivity and residual tumor are the most important prognostic factors in advanced epithelial ovarian cancer.\u003c/p\u003e\n\u003cp\u003eIf patients are platinum-sensitive, both NACT and PCS have similar survival rates, and PCS with no residual tumor increases the success of the treatment in platinum-resistant patients.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eOvarian cancer is the third most common gynecological malignancy in women worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). As it does not cause early symptoms, most of the patients are diagnosed at an advanced stage. Therefore, 5-year life expectancy is lower than 50% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The standard treatment for advanced epithelial ovarian cancer is primary cytoreductive surgery (PCS), followed by platinum-based adjuvant chemotherapy. No visible residual tumor after surgery is one of the most important prognostic factors for survival (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Retrospective studies revealed that optimal cytoreduction (R\u0026thinsp;\u0026lt;\u0026thinsp;1cm) could be achieved in 48\u0026ndash;72% of cases with advanced ovarian cancer with PCS, while complete cytoreduction (R\u0026thinsp;=\u0026thinsp;0) rate was approximately 29\u0026ndash;35% (\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNACT followed by interval cytoreductive surgery (ICS) is preferred as an alternative treatment for patients in whom optimal cytoreduction is assumed not to be achieved due to tumor spread and comorbidity factors. However, still the choice of first-line treatment method in advanced epithelial ovarian cancer has not been clarified. Recent prospective, randomized controlled studies demonstrated that the rate of optimal cytoreduction in NACT is better than in PCS. Whereas, DFS and OS were similar between the PCS and NACT groups (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Several retrospective studies reported that OS was longer in patients with stage IV ovarian cancer who underwent NACT than PCS (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). There is no method to determine platinum sensibility before ovarian cancer treatment. Although some studies show that at the first relapse, the platinum resistance is higher in the NACT than in the PCS group (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), there are also studies that platinum resistance is similar in the first relapse but higher in the second relapse in the NACT group (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of this study is to investigate the outcome of neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery and primary cytoreductive surgery (PCS) in patients with platinum-sensitive or resistant advanced epithelial ovarian cancer.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis observational retrospective study was conducted at Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Obstetrics and Gynecology, Gynecological Oncology Division. The study protocol was approved by the ethical committee (Study number 12.04.2022\u0026ndash;359584).\u003c/p\u003e \u003cp\u003eThe study group consisted of patients who were followed up in our clinic between December 1993 and November 2020, who underwent PCS and then received chemotherapy or received NACT followed by interval cytoreductive surgery. International Federation of Gynecology and Obstetrics (FIGO) stages III-IV epithelial ovarian carcinomas, older than 18, chemotherapy and radiotherapy naive eligible 298 patients\u0026rsquo; files were analyzed retrospectively. One hundred fifty-eight patients were in PCS followed by adjuvant chemotherapy (PCS group), and 140 were in NACT followed by ICS (NACT group). Of the NACT group, 26.4% received three and 34.3% four cycles of chemotherapy. Patients (39.3%) who were considered to have an inadequate response to 3\u0026ndash;4 cycles of chemotherapy by high serum cancer antigene \u0026minus;\u0026thinsp;125 (CA-125) level and radiological examination findings received six cycles of NACT. The exclusion criteria of the study were pregnancy, lactation, non-epithelial ovarian malignancies, borderline ovarian tumors, another known or concurrent malignancy, previous history of chemotherapy due to any kind of tumor, and abdominal or pelvic radiotherapy. In our clinic, the cancer diagnosis was made before NACT, with a tru-cut biopsy of the tumor mass or cytology results of thoracentesis/paracentesis. Eligibility criteria of NACT were: Eastern Cooperative Oncology Group (ECOG) performance status 3\u0026ndash;4, multiple intraparenchymal liver metastases, pulmonary parenchymal metastases, bulky lymphadenopathy (LAP) at the root of the superior mesenteric artery, extensive implants in the small intestine mesentery, metastasis in the porta hepatis and diffuse peritonitis carcinomatosa findings in radiological findings with massive abdominal acid and serum CA-125\u0026thinsp;\u0026gt;\u0026thinsp;1000 U/ml.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eHysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritonectomy, pelvic and/or paraaortic lymphadenectomy, and if necessary organ resections for cytoreduction, were performed.\u003c/p\u003e \u003cp\u003eThe definition of complete cytoreduction is no residual tumor after surgery, optimal cytoreduction is residual tumor less than 1 cm, and suboptimal cytoreduction is residual tumor more than 1 cm. Patients were followed every 3 months for 2 years, every 6 months for 2 to 5 years, and annually after 5 years with gynecological examination and serum CA-125 level. Radiological scans were performed annually or whenever needed. The treatment decision was not made only due to high serum CA-125. The disease's relapse or progression was determined by clinical or radiological findings. Disease-free survival (DFS) was defined as the time between the last dose of platinum-based chemotherapy and recurrence. Overall survival (OS) was described as the period to the date of death or last follow-up. Those that persisted or recurred within the first 6 months after completing the initial treatment were included in the platinum-resistant group, and those that relapsed after 6 months and who have no recurrence were included in the platinum-sensitive group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatsitical analysis\u003c/h2\u003e \u003cp\u003eCollected data were evaluated by IBM SPSS Version 21. The Chi-square and Student's t-test were used to determine the relationship between variables. DFS and OS were estimated using the Kaplan-Meier method and log-rank test. Hazard ratio with 95% confidence interval (CI) was determined for each variable. Cox regression analysis was used to determine prognostic factors on survival. The p-significance value was taken as \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe median follow-up period was 31 months for all patients included in the study. Disease persistence or recurrence was detected in 84.2% (n\u0026thinsp;=\u0026thinsp;251) of all cases, and 62.8% (n\u0026thinsp;=\u0026thinsp;187) of patients died. The distribution of the characteristics of the patients in the PCS and NACT groups was not homogeneous. Age, initial serum CA-125 levels, serous histological type, and stage IV disease rate were significantly higher in the NACT group. While the rate of no residual tumor (R\u0026thinsp;=\u0026thinsp;0) was 47.5% in the PCS group, it was 67.1% in the NACT group (p\u0026thinsp;=\u0026thinsp;0.001). There was no significant difference between menopausal status, BMI, histological grade, and platinum sensibility (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv\u003e\n \u003cdiv align=\"char\"\u003e\u003cbr\u003e\u003cem\u003eTable 1. COMPARISON OF DEMOGRAPHIC CHARACTERISTICS OF PCS AND NACT GROUPS\u003c/em\u003e\u003c/div\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHARACTERISTICS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCS\u0026nbsp;\u003c/strong\u003e(n=158)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNACT\u0026nbsp;\u003c/strong\u003e(n=140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(median -range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e53.1 (28-85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e61.2 (26-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e0,000\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA-125\u003c/strong\u003e (u/ml) (median -range)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e448 (16-13.165)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e1009 (11-30.119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e0,003\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA-125 - n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;1000 u/ml\u003c/p\u003e\n \u003cp\u003e\u0026ge;1000 u/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e99 (74.4)\u003c/p\u003e\n \u003cp\u003e34 (25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65 (47.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72 (52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e (median - range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e29.2 (17-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e29.8 (18-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e0,492\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMENOPAUSE - n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003epremenopause\u003c/p\u003e\n \u003cp\u003epostmenopause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48 (30.4)\u003c/p\u003e\n \u003cp\u003e110 (69.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (20.7)\u003c/p\u003e\n \u003cp\u003e111 (79.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHISTOLOGICAL GRADE - n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003elow grade\u003c/p\u003e\n \u003cp\u003ehigh grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (6.3)\u003c/p\u003e\n \u003cp\u003e148 (93.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (4.2)\u003c/p\u003e\n \u003cp\u003e134 (95.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,601\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHISTOLOGICAL TYPE - n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eserous\u003c/p\u003e\n \u003cp\u003eothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e140 (88.6)\u003c/p\u003e\n \u003cp\u003e18 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e138 (98.6)\u003c/p\u003e\n \u003cp\u003e2 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTAGE - \u0026nbsp;n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e150 (94.9)\u003c/p\u003e\n \u003cp\u003e8 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e116 (82.9)\u003c/p\u003e\n \u003cp\u003e24 (17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLATINUM SENSIBILITY- n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePlatinum-sensitive\u003c/p\u003e\n \u003cp\u003ePlatinum-resistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e90 (59.6)\u003c/p\u003e\n \u003cp\u003e61 \u0026nbsp;(40.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72 \u0026nbsp;(52.6)\u003c/p\u003e\n \u003cp\u003e65 (47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,229\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRESIDUAL DISEASE \u0026nbsp;- \u0026nbsp;n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eR\u0026lt; 1 cm\u003c/p\u003e\n \u003cp\u003eR\u0026ge; 1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e108 (68.4)\u003c/p\u003e\n \u003cp\u003e50 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e126 (90)\u003c/p\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.5679012345679%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRESIDUAL DISEASE - n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eR=0 cm\u003c/p\u003e\n \u003cp\u003eR + cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75 (47.5)\u003c/p\u003e\n \u003cp\u003e83 (52.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.514991181657848%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e94 (67.1)\u003c/p\u003e\n \u003cp\u003e46 (32.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.458553791887127%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe median DFS in all cases was 8 months in the PCS group and 7 months in the NACT group, and there was no difference between the groups (p\u0026thinsp;=\u0026thinsp;0.176; HR: 1.171, 95.0% CI[0.913\u0026ndash; 1.503]). DFS was not evaluated in platinum-resistant cases. In platinum-sensitive patients, there was no significant difference between these two groups (p\u0026thinsp;=\u0026thinsp;0.478; HR: 1.134 95.0% CI[0.793\u0026ndash; 1.620]).\u003c/p\u003e\n\u003cp\u003eThe median OS was 39 months in the PCS group and 26 months in the NACT group, and OS was significantly longer in the PCS than in the NACT group (p\u0026thinsp;=\u0026thinsp;0.016; HR: 1.427, 95.0% CI[1.063.\u0026ndash; 1.914]). In platinum-sensitive cases, there was no OS advantage was observed between the groups (p\u0026thinsp;=\u0026thinsp;0.204; HR: 0.209, 95.0% CI[0.845\u0026ndash; 2.157]). However, in platinum-resistant cases, OS was 21 months in the PCS and 13 months in the NACT group, and OS was significantly longer in the platinum-resistant PCS group (p\u0026thinsp;=\u0026thinsp;0.011; HR: 1.654, 95.0% CI[1.110\u0026ndash; 2.465]), (Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003eA-B).\u003c/p\u003e\n\u003cp\u003eWhen patients with no residual tumor (R\u0026thinsp;=\u0026thinsp;0) in NACT and PCS groups were compared, DFS and OS were significantly longer in the PCS (DFS p\u0026thinsp;=\u0026thinsp;0.009; HR: 1.548, 95.0% CI [1.097\u0026ndash; 2.185] and OS p\u0026thinsp;=\u0026thinsp;0.000; HR: 2.110, 95.0% CI[1.371\u0026ndash; 3.248]). If there was any residual tumor, there was no significant difference between the two groups (DFS, p\u0026thinsp;=\u0026thinsp;0.547; HR: 1.099, 95.0% CI [0.753\u0026ndash; 1.604] and OS, p\u0026thinsp;=\u0026thinsp;0.198; HR:1.318, 95.0% CI[0.861\u0026ndash; 2.017]) (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003eA-B).\u003c/p\u003e\n\u003cp\u003eIn terms of platinum sensibility, sub-group analysis revealed no OS advantage between PCS and NACT groups in platinum-sensitive cases with or without residual tumor. In platinum-resistant R\u0026thinsp;=\u0026thinsp;0 cases, the median OS was 41.5 months in the PCS and 16 months in the NACT group, significantly longer in the PCS (OS, p\u0026thinsp;=\u0026thinsp;0.008; HR: 3.303, 95.0% CI [1.295\u0026ndash; 8.430]). Whereas, in platinum-resistant R\u0026thinsp;+\u0026thinsp;patients, no statistically significant difference was found between the groups (OS, p\u0026thinsp;=\u0026thinsp;0.091; HR: 1.515, 95.0% CI[0.927\u0026ndash; 2.475]),(Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003eA-B).\u003c/p\u003e\n\u003cp\u003eThe characteristics of the patients such as age, BMI, serum CA-125 level, menopausal status, and histological grade were evaluated with Kaplan Meier log-rank \u0026chi;2 analysis, and no significant difference was found in DFS and OS (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv\u003e\n \u003cdiv align=\"left\"\u003e\u003cem\u003eTable 2. KAPLAN MEIER SURVIVAL ANALYSIS OF CHARACTERISTICS\u003c/em\u003e\u003c/div\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.095588235294116%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.1764705882353%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.72794117647059%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003eMEAN\u003c/p\u003e\n \u003cp\u003e( month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003eMEDIAN\u003c/p\u003e\n \u003cp\u003emonth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003eMEAN\u003c/p\u003e\n \u003cp\u003e(month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003eMEDIAN\u003c/p\u003e\n \u003cp\u003emonth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTREATMENT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePCS (n=158)\u003c/p\u003e\n \u003cp\u003eNACT (n=140)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13.9%\u003c/p\u003e\n \u003cp\u003e10.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45.7\u003c/p\u003e\n \u003cp\u003e31.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40.5%\u003c/p\u003e\n \u003cp\u003e31.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.025\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRESIDUAL DISEASE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eR=0 (n=169)\u003c/p\u003e\n \u003cp\u003eR +(n=129)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.2\u003c/p\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.2%\u003c/p\u003e\n \u003cp\u003e8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45.6\u003c/p\u003e\n \u003cp\u003e30.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46.3%\u003c/p\u003e\n \u003cp\u003e23.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLATINUM SENSIBILITY\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePlatinum-sensitive (n=162)\u003c/p\u003e\n \u003cp\u003ePlatinum-resistant (n=126)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28.3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21,9%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52.9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56.3%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026le; 58 (n=144)\u003c/p\u003e\n \u003cp\u003e\u0026gt; 58 (n=154)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15.8\u003c/p\u003e\n \u003cp\u003e15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.5%\u003c/p\u003e\n \u003cp\u003e15.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e42.8\u003c/p\u003e\n \u003cp\u003e35.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003cp\u003e28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e42.4%\u003c/p\u003e\n \u003cp\u003e30.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.355\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 30 (n=152)\u003c/p\u003e\n \u003cp\u003e\u0026ge; 30 (n=146)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14.2%\u003c/p\u003e\n \u003cp\u003e10.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37.1\u003c/p\u003e\n \u003cp\u003e41.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003cp\u003e34.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34.6%\u003c/p\u003e\n \u003cp\u003e37.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMENOPAUSE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePre (n=77)\u003c/p\u003e\n \u003cp\u003ePost (n=221)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.7\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.7%\u003c/p\u003e\n \u003cp\u003e14.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.3\u003c/p\u003e\n \u003cp\u003e39.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40.3%\u003c/p\u003e\n \u003cp\u003e35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.850\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA-125 u/ml\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;1000(n=164)\u003c/p\u003e\n \u003cp\u003e\u0026ge;1000(n=106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15.4\u003c/p\u003e\n \u003cp\u003e13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13.7%\u003c/p\u003e\n \u003cp\u003e8.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003cp\u003e35.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34.1%\u003c/p\u003e\n \u003cp\u003e36.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHISTOLOGICAL GRADE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLow (n=16)\u003c/p\u003e\n \u003cp\u003eHigh (n=282)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17.4\u003c/p\u003e\n \u003cp\u003e15.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.5\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.5%\u003c/p\u003e\n \u003cp\u003e12.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52.4\u003c/p\u003e\n \u003cp\u003e38.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39.5\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41.3%\u003c/p\u003e\n \u003cp\u003e36%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.638\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTAGE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIII (n=266)\u003c/p\u003e\n \u003cp\u003eIV (n=32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.6\u003c/p\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.9%\u003c/p\u003e\n \u003cp\u003e10.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40.8\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37.2%\u003c/p\u003e\n \u003cp\u003e27.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.41544885177453%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHISTOLOGICAL TYPE\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSerous (n=278)\u003c/p\u003e\n \u003cp\u003eOthers (n=20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.526096033402922%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.5\u003c/p\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.8%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.1419624217119%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.734864300626304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40.3\u003c/p\u003e\n \u003cp\u003e21.8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.22964509394572%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.18580375782881%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37.2%\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.350730688935283%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eWhen the parameters were evaluated by multivariate Cox Regression analysis, platinum-sensitive disease (HR: 4.138, 95% CI [2.982\u0026ndash;5.743]; p\u0026thinsp;=\u0026thinsp;0.000), PCS as the first treatment (HR: 1.612, 95% CI [1.195\u0026ndash;2.176]; p. =0.002), and no residual tumor after surgery (HR: 1.430, 95% CI [1.040\u0026ndash;1.966]; p\u0026thinsp;=\u0026thinsp;0.027) were determined as the most significant independent prognostic factors.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSummary of Main Results\u003c/h2\u003e \u003cp\u003eStandard treatment in advanced ovarian cancer is PCS, followed by adjuvant chemotherapy. In the preoperative evaluation of patients with suspected stage III-IV epithelial ovarian cancer, laparoscopic, radiological, and biochemical findings can be combined with scoring systems for surgery suitability (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Wright et al. recommended that NACT was preferred only in patients with a high perioperative risk profile and a low chance of achieving optimal cytoreduction in PCS (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). However, there are also studies indicating that 5\u0026ndash;12% of the patients have a complete response after NACT, and the prognosis in these patients is excellent (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In our study, no significant difference was observed in DFS between the PCS and NACT groups.\u003c/p\u003e \u003cp\u003eNevertheless, similar to most retrospective studies, OS was significantly longer in the PCS group. Considering those without residual tumor after surgery, survival was better in the PCS group than in the NACT group. There was no survival advantage between NACT vs PCS groups in platinum-sensitive patients. This result eliminates the importance of PCS as a first treatment option in platinum-sensitive cases. Since the surgical complication rate is generally low in the NACT, applying NACT as a first-line treatment can be a good option if the patient is platinum-sensitive. Even whether the patient is chemo-sensitive or \u0026ndash;resistant is not known initially.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eResults in the Context of Published Literature\u003c/h3\u003e\n\u003cp\u003eMost retrospective studies revealed that PCS provides DFS and OS advantages over NACT. In the study by Rauh-Hain et al., which searched the US National Cancer Database and selected 2935 similar cases for both groups, the median OS was found to be 37.3 months in the PCS group and 32.1 months in the NACT group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Lyons et al. published a retrospective analysis of approximately 37.000 patients in the National Cancer Database, and the OS was longer in the PCS group (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In another retrospective cohort study conducted by Matsuo et al., queried by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER), ovarian cancer mortality (3-year cumulative incidence) was 41.9% in the PCS and 47.5% in the NACT group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Gao et al. found a difference of 5.5 months in DFS and 15.5 months in OS between two groups in favor of the PCS. However, no statistically significant difference was observed (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, the decision of PCS or NACT was determined according to the initial clinical and radiological findings. In the NACT group, tumor load was rather extensive, patients were old, initial serum CA-125 levels were high, and the number of patients with stage IV and ECOG performance scores of 3\u0026ndash;4 with comorbidities were much higher than in the PCS group. The distribution of patient characteristics between the two groups was non-homogeneous; that was the crucial bias in our study.\u003c/p\u003e \u003cp\u003eProspective randomized trials have also been administered for NACT as an alternative therapy in advanced ovarian cancer. The first was completed in 2010 by the European Gynecological Cancer Research and Treatment Group (EORTC-GCG 55791). Although complete tumor resection was 19.4% in PCS and 51.2% in NACT, there was no significant difference in DFS and OS. No residue tumor was the most important independent prognostic factor (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In another randomized controlled phase 3 trial, CHORUS was published in 2015, the complete cytoreduction rate was 17% in PCS and 39% in NACT, and there was no statistically significant difference in DFS and OS. It has been suggested that NACT was a good alternative treatment, especially in cases with low-performance scores, due to its lower morbidity and mortality rates (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe prospective, randomized, controlled phase 3 study SCORPION was emitted in 2020. The complete cytoreduction rate was 47.6% in PCS and 77% in the NACT group, and there was no significant difference between DFS and OS. However, postoperative death and major complication rates were significantly higher in the PCS group than in the NACT group (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlso, in the prospective randomized study (JCOG 0602) of the Japanese Gynecological Oncology Group issued in 2020, complete resection was found to be 12% in the PCS and 64% in the NACT group. The median DFS was 15.1 months in the PCS, 16.4 months in the NACT group, and the median OS was 49 months in the PCS and 44.3 months in the NACT group. The result of this study was a little different compared to other prospective randomized studies, and the authors concluded that a survival noninferiority of NACT was not confirmed in their study compared with PCS. NACT might not be replaced every time for PCS (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In retrospective studies, survival was better in the PCS group; randomized and prospective studies revealed that survival outcomes in the NACT group are non-inferior to PCS. The results of incoming studies (TRUST (Clinical Trial NCT02828618) and SOC-2 (Clinical Trial NCT02859038)) have not been published yet.\u003c/p\u003e \u003cp\u003eNo residual tumor after surgery is an important prognostic factor for survival. Recent studies have shown that ICS after NACT provides a high complete/optimal cytoreduction rate and less surgical morbidity (\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). In our study, the rates of no residual tumor (R\u0026thinsp;=\u0026thinsp;0) between the two groups favored the NACT group, similar to randomized controlled studies. DFS and OS were longer in R\u0026thinsp;=\u0026thinsp;0 patients in the PCS group. DFS and OS were similar to the NACT group in the PCS group with residual tumors. Although there was no statistically significant result in two different retrospective studies, the tendency of OS advantage was found in the PCS group with no residual tumor (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePlatinum sensitivity is as important as no residual tumor in advanced ovarian cancer. However, there is still no marker that can be used in practice to predict platinum sensibility. On the other hand, ATP-dependent transporter gene (ABCB1), ATP binding cassette G2 (ABCG2) overexpression with Wnt/b-catenin pathway, astrocyte elevated gene-1 (AEG-1) expression, PI3K/Akt/mTOR pathway activation and TP53 K351N, PTEN, BRCA1/2, KRAS, BRAF, β-catenin gene mutations and chromosome instability are associated with platinum resistance (\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs most patients have both platinum-sensitive and platinum-resistant cells at the first diagnosis, approximately 80% of newly diagnosed epithelial ovarian cancer cases respond to first-line platinum-based chemotherapy. Despite this, approximately 70% of patients relapse, and most turn to the platinum-resistant phase (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In our study, the rate of platinum resistance was 40.4% in the PCS and 47.4% in the NACT group.\u003c/p\u003e \u003cp\u003eLarge tumors are poorly vascularized, and they are hypoxic and necrotic. The higher the tumor burden at the start of treatment, the greater the probability of tumor mutation and platinum resistance. Reducing the tumor burden with PCS minimizes the number of cells that can transform into platinum-resistant phenotypes. If the treatment is started with NACT, tumor cells have more probability of developing a platinum-resistant phase. Due to this condition, NACT is suggested not to be as effective as desired (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to Liu et al., most studies are limited because they are retrospective and biased in patient selection criteria, so it is difficult to conclude that NACT increases the likelihood of platinum resistance. However, the possibility of NACT causing more platinum resistance should not be ignored (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Weaknesses\u003c/h2\u003e \u003cp\u003eOur weaknesses are the non-homogeneous patient characteristics between the two groups and the retrospective study. Our strengths are the sufficient follow-up period and the number of patient groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImplications for Practice and Future Research\u003c/h2\u003e \u003cp\u003eWe could not find a study in the literature that PCS provides a survival advantage in chemotherapy-resistant patients. New studies are needed to compare our results. In addition, a method should be developed to determine the disease's sensitivity to chemotherapy.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWe revealed that if the patient is platinum-sensitive, PCS as a first-line treatment was not essential because NACT could be used effectively.\u003c/p\u003e \u003cp\u003eOn the other hand, in platinum-resistant with R\u0026thinsp;=\u0026thinsp;0 cases, the PCS as the first treatment provides a better survival advantage. The problem is that we make the initial treatment selection based on clinical findings, and we cannot detect platinum sensibility before starting treatment. Detection of a specific method that determines platinum sensibility is a critical issue in ovarian cancer. If platinum resistance can be assigned before treatment, it would be more rational to prefer PCS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFUNDING\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated in this study are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests :\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non- financial interests to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional review board statement: \u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the ethical committee (Study number 12.04.2022 - \u0026nbsp;359584).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent statement:\u0026nbsp;\u003c/strong\u003eInformed consent was waived due to the retrospective study design. Patient data were anonymized at the time of collection and patient identification is not possible.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTION\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBOK and TB have made significant contributions to the design and acquisition, analysis, and interpretation of data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors participated in the drafting and revision of the article, gave consent for publication of the article, and confirmed the accuracy of the data and analysis and the adequacy of the protocol of the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGlobocan 2020 The Global Cancer Observatory - All Rights Reserved, March, 2021. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf\u003c/li\u003e\n\u003cli\u003eDe Angelis R et al (2014) Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol 15(1):23\u0026ndash;34\u003c/li\u003e\n\u003cli\u003eWinter WE 3rd et al (2007) Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25(24): 3621\u0026ndash;3627\u003c/li\u003e\n\u003cli\u003eWinter WE 3rd et al (2008) Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 26(1): 83\u0026ndash;89\u003c/li\u003e\n\u003cli\u003edu Bois A et al (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d\u0026apos;Investigateurs Nationaux pour les Etudes des cancers de l\u0026apos;Ovaire (GINECO). Cancer 115(6):1234\u0026ndash;1244\u003c/li\u003e\n\u003cli\u003eMay T et al (2017) A comparison of survival outcomes in advanced serous ovarian Cancer patients treated with primary Debulking surgery versus neoadjuvant chemotherapy. Int J Gynecol Cancer 27(4):668\u0026ndash;674\u003c/li\u003e\n\u003cli\u003eLyons YA et al (2020) Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy. Int J Gynecol Cancer 30(6):845\u0026ndash;852\u003c/li\u003e\n\u003cli\u003eMatsuo K et al (2021) Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer. Gynecol Oncol 160(1):32\u0026ndash;39\u003c/li\u003e\n\u003cli\u003eGao Y et al (2019) Evaluating the benefits of neoadjuvant chemotherapy for advanced epithelial ovarian cancer: a retrospective study. J. Ovarian Res 12(1):85\u003c/li\u003e\n\u003cli\u003eTseng JH et al (2018) Continuous improvement in primary Debulking surgery for advanced ovarian cancer: Do increased complete gross resection rates independently lead to increased progression-free and overall survival? Gynecol Oncol 151(1): 24-31\u003c/li\u003e\n\u003cli\u003eVergote I et al (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363(10):943\u0026ndash;953\u003c/li\u003e\n\u003cli\u003eKehoe S et al (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. The Lancet 386(9990):249\u0026ndash;257\u003c/li\u003e\n\u003cli\u003eFagotti A et al (2020) Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int J Gynecol Cancer 30(11):1657\u0026ndash;1664\u003c/li\u003e\n\u003cli\u003eTajik P et al (2018) The FIGO stage IVA versus IVB of ovarian Cancer: prognostic value and predictive value for neoadjuvant chemotherapy. Int J Gynecol Cancer 28(3):453\u0026ndash;458\u003c/li\u003e\n\u003cli\u003eHou JY et al (2007) Neoadjuvant chemotherapy lessens surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease. Gynecol Oncol 105(1):211\u0026ndash;217\u003c/li\u003e\n\u003cli\u003eLuo Y et al (2016) Effect of neoadjuvant chemotherapy on platinum resistance in stage IIIC and IV epithelial ovarian cancer. Medicine (Baltimore) 95(36):e4797\u003c/li\u003e\n\u003cli\u003eMakar AP et al (2016) Advanced ovarian Cancer: primary or interval Debulking? Five categories of patients in view of the results of randomized trials and tumor biology: primary Debulking surgery and interval Debulking surgery for advanced ovarian Cancer. Oncologist 21(6):745\u0026ndash;754\u003c/li\u003e\n\u003cli\u003ePetrillo M et al (2013) Timing and pattern of recurrence in ovarian cancer patients with high tumor dissemination treated with primary debulking surgery versus neoadjuvant chemotherapy. Ann Surg Oncol 20(12):3955\u0026ndash;3960\u003c/li\u003e\n\u003cli\u003eRauh-Hain JA et al (2013) Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma. Gynecol Oncol 129(1):63\u0026ndash;68\u003c/li\u003e\n\u003cli\u003eda Costa AA et al (2015) Neoadjuvant chemotherapy followed by interval Debulking surgery and the risk of platinum resistance in epithelial ovarian Cancer. Ann Surg Oncol 22(3):S971\u0026ndash;978\u003c/li\u003e\n\u003cli\u003eFagotti A et al (2008) Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am. J. Obstet. Gynecol 199(6):642.e1\u0026ndash;642.e6\u003c/li\u003e\n\u003cli\u003eQin L et al (2018) Clinical study of a CT evaluation model combined with serum CA125 in predicting the treatment of newly diagnosed advanced epithelial ovarian cancer. J Ovarian Res 11(1):49\u003c/li\u003e\n\u003cli\u003eWright AA et al (2016) Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. Gynecol Oncol 143(1):3-15\u003c/li\u003e\n\u003cli\u003eMichaan N et al (2018) Prognostic value of pathologic chemotherapy response score in patients with ovarian Cancer after neoadjuvant chemotherapy. Int J Gynecol Cancer 28(9):1676\u0026ndash;1682\u003c/li\u003e\n\u003cli\u003ePetrillo M et al (2014) Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer. Am J Obstet Gynecol 211(6):632.e1\u0026ndash;e8\u003c/li\u003e\n\u003cli\u003eRauh-Hain JA et al (2017) Neoadjuvant Chemotherapy Compared with Primary Cytoreductive Surgery in Women with Epithelial Ovarian Cancer: Analysis of the National Cancer Database. JAMA Oncol 3(1):76\u0026ndash;82\u003c/li\u003e\n\u003cli\u003eOnda T et al (2020) Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers in phase III randomised trial. Eur J Cancer 130:114-125\u003c/li\u003e\n\u003cli\u003eXiao Y et al (2018) Platinum-based neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma International Federation of Gynecology and Obstetrics Stages IIIc and IV: a systematic review and meta-analysis. Gynecol Obstet Investig 83(3):209\u0026ndash;219\u003c/li\u003e\n\u003cli\u003eLeary A et al (2016) Primary surgery or neoadjuvant chemotherapy in advanced ovarian cancer: the debate continues. Am Soc Clin Oncol Educ Book 35:153\u0026ndash;162\u003c/li\u003e\n\u003cli\u003eChau W et al (2013) c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/beta-catenin-ATP- binding cassette G2 signaling. Oncogene 32(22):2767\u0026ndash;2781\u003c/li\u003e\n\u003cli\u003ePark JT et al (2010) Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am. J. Pathol 177(3):1087\u0026ndash;1094\u003c/li\u003e\n\u003cli\u003eZhang GN et al (2014) TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer. Gynecol Oncol 132(13):752\u0026ndash;757\u003c/li\u003e\n\u003cli\u003ePatch AM et al (2015) Whole-genome characterization of chemoresistant ovarian cancer. Nature 521(7553):489\u0026ndash;494\u003c/li\u003e\n\u003cli\u003eTakaya H et al (2020) Intratumor heterogeneity and homologous recombination deficiency of high-grade serous ovarian cancer are associated with prognosis and molecular subtype and change in treatment course. Gynecol Oncol 156(2):415\u0026ndash;422\u003c/li\u003e\n\u003cli\u003eLiu J, Jiao X, Gao Q (2020) Neoadjuvant chemotherapy-related platinum resistance in ovarian cancer. Drug Discovery Today 25(7):1232-1238\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"primary cytoreduction, interval cytoreduction, platinum-resistance, platinum-sensitive, residual tumor","lastPublishedDoi":"10.21203/rs.3.rs-4587958/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4587958/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: We investigated the outcome of neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery and primary cytoreductive surgery (PCS) in patients with platinum-sensitive or resistant advanced epithelial ovarian cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods:\u003c/strong\u003e The inclusion criteria fit 298 patients who underwent primary cytoreductive surgery (PCS group n=158) or neoadjuvant chemotherapy (NACT group n=140). Differences in characteristic features, chemotherapy responses, and prognosis were compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Although the median DFS was similar between the two groups, the median OS was significantly longer in the PCS (p=0.025). There was no survival advantage between the two groups regarding OS in platinum-sensitive patients. However, OS was significantly longer in platinum-resistant patients who underwent PCS (p=0.011). The rate of complete cytoreduction (R=0) was 47.5% in the PCS and 67.1% in the NACT group (p=0.001). Although DFS and OS advantages were observed in the PCS group in R=0 patients with a residual tumor, no significant difference was noticed between the two groups. The two groups had no OS advantage when platinum-sensitive patients were assessed for residual tumor. Meanwhile, in platinum-resistant patients, R=0 provided OS advantage in the PCS group (p=0.008). However, no significant difference was observed if there was any residual tumor (p=0.091).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e OS was significantly longer in the PCS group. Survival is better in platinum-resistant patients if no residual tumor exists after PCS. There was no difference in OS between the PCS and NACT groups in platinum-sensitive patients, regardless of residual tumor. Specific methods and markers are needed before initial treatment in epithelial ovarian cancer.\u003c/p\u003e","manuscriptTitle":"Primary Cytoreductive Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: the Primary Cytoreductive Surgery is Better Than Neoadjuvant Chemotherapy in Platinum-resistant Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 22:06:05","doi":"10.21203/rs.3.rs-4587958/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b0c46533-5318-4383-aa8e-34fa9c3637d2","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-19T18:53:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-23 22:06:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4587958","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4587958","identity":"rs-4587958","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}