Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer

Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer | 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 Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer yusuke toyohara, Atsushi Fusegi, Motoko Kanno, Sachiho Netsu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6127970/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Sep, 2025 Read the published version in Journal of Obstetrics and Gynaecology Research → Version 1 posted You are reading this latest preprint version Abstract Background Bowel mucosal invasion epithelial ovarian cancer (EOC) is classified as stage IVB disease. The reason for this classification remains unclear, and clinical data on bowel mucosal invasion in EOC should be investigated. Methods We retrospectively reviewed data from patients with stage IVB EOC who presented at our hospital with bowel mucosal invasion between January 2011 and September 2023. Patients with bowel mucosal invasion and other factors associated with IVB EOC were excluded from the study. The primary and secondary considerations were progression-free survival (PFS) and overall survival (OS), respectively. Results Two-hundred fifty-four patients were diagnosed with stage IVB EOC. Among these, 23 (9.1%) patients had bowel mucosal invasion, and 13 (5.1%) were diagnosed with stage IVB EOC based on bowel mucosal invasion alone. The median follow-up period was 40.5 months (range, 14.9–81.6 months). PDS was performed in nine patients (69.2%), NAC-IDS in four (30.8%), and R0 resection was achieved in all of the 13 patients without other stage IVB-related factors. Among those patients, the 3-year PFS and OS rates were 54.9% and 82.1%, respectively. Conclusion We have shown that in cases of bowel mucosal invasion, complete resection may be possible and the prognosis of these patients may be better than in the general population at stage IVB. Based on these observations, we believe that bowel mucosal invasion by itself is not a potential prognostic factor for stage IVB ovarian cancer. epithelial ovarian cancer cancer stage cytoreduction surgical procedures neoplasm invasiveness stage IVB Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Every year, 300,000 women worldwide are newly diagnosed with epithelial ovarian cancer (EOC) [ 1 ]. EOC is the fifth leading cause of cancer-related death in women [ 2 ] and the leading cause of death in women with gynecological cancer [ 2 ], with two-thirds of patients being diagnosed with advanced-stage tumors [ 3 ]. In addition to the use of high-dose surgical cytoreductive and platinum-plus-taxane-based chemotherapy, novel treatment modalities such as bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors have been introduced, leading to improved prognosis. Despite these advances, 5-year overall survival (OS) in advanced EOC has not reached 50% [ 4 ]. For advanced-stage EOC, either interval debulking surgery after neoadjuvant chemotherapy (NAC-IDS) or primary debulking surgery (PDS) followed by adjuvant chemotherapy were taken into consideration. In PDS and NAC-IDS, the most important prognostic factor is the absence of residual disease (R0) after surgery [ 3 , 5 , 6 ]. Evidence on the benefit of surgery in stage IVB is limited as most randomized controlled trial analyses for stage IVB are subgroup analyses [ 7 , 8 ]. Stage IVB is generally considered to be a systemic condition, and therefore NAC-IDS is often used for Stage IVB since resection of R0 is not considered possible in PDS. The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification (FIGO2014) categorized ovarian cancer with bowel mucosal invasion as stage IVB [ 9 ] and the reasons for this classification remain unclear. A few studies have reported that bowel mucosal invasion is not a prognostic factor for stage IVB [ 10 , 11 ]; however, the prognostic effect of bowel mucosal invasion remains uncertain, as the incidence is rare, occurring in approximately 5% of patients with stage IVB EOC [ 9 , 12 ]. While the appropriate treatment of Stage IVB is still being considered, there are other resectable sites of disease, such as the cardiophrenic and inguinal lymph nodes, which are classified as stage IVB in FIGO2014 and several studies suggested resection of those lesions are feasible and reconsidering the classification [ 13 , 14 , 15 ]. Similarly, a full resection of stage IVB EOC with bowel mucosal invasion may improve prognosis. In this study, we examined EOC cases with bowel mucosal invasion and evaluated the validity of the classification for these events. PATIENTS AND METHODS Patient selection This study was designed as a retrospective cohort review and included patients with stage IVB FIGO2014 EOC (including epithelial ovarian, fallopian tube, and peritoneal cancer) due to bowel mucosal invasion. Patients were treated at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between January 2011 and September 2023. Both patients with mucosal invasion of the appendix alone and those with bowel mucosal invasion in addition to other characteristics linked to stage IVB EOC, such as parenchymal metastases, were excluded. Pre-treatment diagnosis was based on computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT findings. Board-certified pathologists have obtained histopathological evidence of bowel mucosal invasion from surgical samples or biopsies. The surgical procedures were based on disease distribution. According to the surgeon who carried out the procedure, R0 resection was defined as having no residual disease following surgery; if there were residual lesions, the status was classified as nonR0. The Clavien–Dindo classification was used for the evaluation of post-operative complications, with grade III or higher were being reported [ 16 ]. Chemotherapies, followed by maintenance therapies such as PARP inhibitors or bevacizumab, were administered at the physician’s discretion. Endpoints The primary endpoint was progression-free survival (PFS), calculated from the end date of primary treatment to the date of diagnosis of progression or recurrence, at the end of last follow-up, or at the end of September 2024, and the secondary endpoint was overall survival (OS), calculated from the date of diagnosis of EOC to the date of death, last follow-up, or September 2024. Recurrence or progression of EOC was diagnosed by imaging or by biopsy. The follow-up period was from the date of diagnosis until the date of death, whichever was the earliest, the last follow-up, or September 2024. Patient variables We evaluated the following variables: age, body mass index (kg/m 2 ), cancer type, histopathological type, mucosal invasion site, primary treatment types, surgical procedures, resection status after primary treatment, chemotherapy types and maintenance therapy for first-line treatment, PFS, OS, and recurrence sites. Age, BMI (kg/m2), cancer type, histopathological type, mucosal invasion site, primary treatment types, surgical procedures, resection status following primary treatment, types of chemotherapy and maintenance therapy for first-line treatment, PFS, OS, and recurrence sites were among the variables we assessed. Statistics We estimated OS and PFS for the survival analysis using the Kaplan–Meier estimator. Statistical analyses were performed in R (version 4.1.2). Ethics The Institutional Review Board at the Cancer Institute Hospital of Japanese Foundation for Cancer Research approved this study (approval number: 2023-GB-079). Owing to the anonymization of the data, the requirement for informed consent was waived. RESULTS Between 2011 and 2023, 254 patients in our institutions were diagnosed with stage IVB EOC, 23 of whom were diagnosed with bowel mucosal invasion (9.1%). Thirteen patients were diagnosed with stage IVB EOC based solely on bowel mucosal invasion, and ten patients were assigned to stage IVB based on additional features. Therefore, 5.1% of patients with stage IVB EOC were diagnosed with stage IVB EOC solely on the basis of the bowel mucosal invasion (Fig. 1 ).Table 1 lists the patient characteristics. Median duration of follow-up was 40.5 months (range 14.9 to 81.6 months). Ten patients (76.9%) had high-grade serous carcinoma (HGSC), followed by two (15.4%) with clear cell carcinoma, one (7.7%) with endometrioid carcinoma. The most common site of bowel mucosal invasion was the rectum (46.1%), followed by the sigmoid colon (30.8%). Cytoreductive surgery was performed in all patients and PDS in nine patients (69.2%) and NAC-IDS in four (30.8%). R0 resection was achieved in all patients. The surgical procedures are listed in Table S1, and Fig. 2 shows an example of a tumor resection with low anterior resection of the rectum. One patient (7.7%) had small intestinal resection, two (15.4%) had transverse colon resection, twelve patients (92.3%) had low anterior resection, and one (7.7%) had ileocecal resection. All patients received adjuvant chemotherapy and four of them (30.8%) received maintenance therapy (two with PARP inhibitor plus bevacizumab, two with PARP inhibitor). Table 1 Patient characteristics Bowel mucosal invasion alone (n = 13) Age, median, years (range) 58 (33–79) BMI, median (range) 19.6 (15.5–23.0) Primary site of disease, n (%) Ovarian 8 (61.5) Fallopian 2 (15.3) Peritoneal 3 (23.1) Histopathological types, n (%) HGSC 10 (76.9) Endometrioid carcinoma 1 (7.7) Clear cell carcinoma 2 (15.4) Site of mucosal invasion, n (%) Rectum 6 (46.1) Sigmoid colon 4 (30.8) Transverse colon 2 (15.4) Cecum 1 (7.7) History of cytoreductive surgery, n (%) PDS 9 (69.2) NAC-IDS 4 (30.8) No surgery 0 (0.0) Residual disease, n (%) No 13 (100.0) Yes 0 (0.0) BMI, body mass index; HGSC, high-grade serous carcinoma; PDS, primary debulking surgery; NAC-IDS, neoadjuvant chemotherapy and interval debulking surgery. Five patients (38.5%) had a recurrence of disease and two patients (15.4%) died. The most common metastasis sites were peritoneum (23.1%), followed by liver (15.4%) and lymph nodes (15.4%). Figures 3 a and 3 b illustrate the Kaplan–Meier plots for PFS and OS. The 3-year PFS and OS rates were 54.9% and 82.1%, respectively. Median PFS and OS were not reached. Postoperative complications occurred in three patients (23.1%), and no patient died during the perioperative period as a result of postoperative complications. All patients experienced postoperative complications recovered well and all of them could receive subsequent adjuvant chemotherapy. DISCUSSION In this study, we investigated the characteristics of stage IVB EOC caused by bowel mucosal invasion. In our cohort, the incidence of stage IVB EOC due to bowel mucosal invasion alone was 5.1%. Due to bowel mucosal invasion alone, we were able to achieve R0 resection in every patient with stage IVB EOC. The 3-year PFS and OS rates were 54.9% and 82.1%, respectively. Previously, the 5-year survival rates and median OS for stage IVB EOC ranged from 11.7–38% and 23 to 48 months, respectively [ 6 , 9 , 12 , 17 , 18 ] and the 5-year survival rates of stage III EOC were 22 to 54.3% [ 6 , 17 , 19 ]. In our data, the 3- and 5-year PFS and OS rates were similar, and the prognosis in our study for patients with stage IVB EOC due to bowel mucosal was relatively better than that for patients with stage IVB and even stage III EOC, as previously reported. We considered that this might be because R0 resection was achieved in all patients diagnosed with stage IVB EOC due to bowel mucosal invasion alone. Therefore, our data suggested bowel mucosal invasion may not be considered as a factor in the stage IVB EOC. Bowel mucosal invasion did not demonstrate prognostic potential for stage IVB EOC cancer in this investigation. Limited evidence is inconclusive, with some studies supporting bowel mucosal invasion as a prognostic factor and others opposing it (Table 2 ) [ 10 , 11 , 20 , 21 ]. Giorgio et al. reported that deep bowel invasion is a prognostic factor (5-year survival rates of invasion with serous, muscular, and mucosal layers were 72.7%, 33.1%, and 0%, respectively), supporting the FIGO2014 classification [ 20 ]. By contrast, Mert et al. reported a longer PFS and OS in the group with bowel invasion of the muscle, submucosal, or mucosal layer than in the group with serosal or subserosal invasion (PFS, 33.5 and 18.2 months; OS, 82.3 and 51.5 months, respectively; not significant). This suggests that a deeper invasion to the bowel is not a prognostic factor of stage IVB disease [ 10 ]. We concentrated on the prognosis in stage IVB EOC due to bowel mucosal invasion in primary treatment because of the limited evidence, and we think that factors for categorizing bowel mucosal invasion in EOC are crucial. Table 2 Literature review The plus symbols indicate those that support bowel mucosal invasion given the prognostic evidence for stage IVB epithelial ovarian cancer and the minus symbols indicate those that oppose it. Year Journal Total number of patients (primary therapy) Number of patients with mucosal bowel invasion Significance Mucosal bowel invasion as prognostic factor 2006 Gynecol Oncol. 46 13 including muscularis invasion PFS of patients with serosa/subserosa invasion was longer than that of muscularis/mucosa (26 vs 7 months, p = 0.176) + 2011 Eur J Surg Oncol. 71 12 Depth of bowel wall invasion was not associated to PFS and OS. - 2013 World J Surg Oncol. 52 4 Depth of bowel wall invasion is associated to 5-year survival (serosal: 72.7%, muscularis: 33.1%, mucosa: 0% p = 000.4) + 2019 Gynecol Oncol. 85 17 including submucosal invasion PFS and OS of patients with muscularis/submucosa/mucosa invasion were longer those of serosal/subserosal invasion (median PFS, 33.5 vs. 18.2 months, p = 0.34; median OS, 82.3 vs. 51.5 months, p = 0.46) - Although the prognosis for advanced EOC has improved with PARP inhibitors, the importance of surgical therapy remains because R0 resection is a significant prognostic factor even after the use of pharmacological interventions [ 6 , 22 ]. In a study of stage IVB EOC, the prognosis of patients who underwent PDS with R0 resection was better than that of the other groups (PDS without R0 resection, NAC-IDS, or chemotherapy only) [ 18 ]. Although the EORTC 55971 and CHORUS trials' pooled analysis indicated that NAC-IDS produced favorable outcomes compared with PDS [ 6 ], Jochum et al. examined 2772 stage IV EOC patients, and PDS showed better results than NAC-IDS, particularly for patients with extra-abdominal lymph node, supradiaphragm, or pleural metastases. [ 23 ]. Because heterogeneity exists among stage IVB EOC, comprehensive studies of the prognostic factors for stage IVB EOC are needed. This study had some limitations. First, it was a retrospective single-center, single-arm study with a limited number of patients and follow-up duration. Therefore, various confounding factors, such as BRCA and homologous recombination status, could not be adjusted for. Second, due to the approval of new treatments such as PARP inhibitors and bevacizumab, treatment modalities have changed between patients. Therefore, long-term prognosis in patients with stage IVB EOC with bowel mucosal invasion should be evaluated after the adoption of the new strategy. CONCLUSION This research focused on the outlook for patients diagnosed with stage IVB EOC caused by bowel mucosal invasion. It was found that R0 resection is a feasible option, and if this is achieved, the prognosis for these patients is more hopeful than the general population diagnosed with stage IVB. Thus, bowel mucosal invasion does not have the potential to be a prognostic factor for stage IVB EOC. Declarations All authors have no competing interests to disclose. Author contributions Yusuke Toyohara: data curation, investigation, formal analyses, methodology, visualization, writing (original draft), writing (review and editing). Atsushi Fusegi: conceptualization, data curation, funding acquisition, methodology, project administration, writing (original draft), writing (review and editing). Motoko Kanno: methodology, supervision, writing (review and editing). Sachiho Netsu: data curation, writing (review and editing). Terumi Tanigawa: methodology, supervision, writing (review and editing). Mayu Yunokawa: methodology, supervision, writing (review and editing). Hiroyuki Kanao: supervision, writing (review and editing). ACKNOWLEDGMENTS The authors thank Editage for English language editing ( https://www.editage.com/ ). No specific funding was provided for this study. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249 Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. 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Gynecol Oncol153:238 – 41 Park JY, Seo SS, Kang S, Lee KB, Lim SY, Choi HS et al (2006) The benefits of low anterior en bloc resection as part of cytoreductive surgery for advanced primary and recurrent epithelial ovarian cancer patients outweigh morbidity concerns. Gynecol Oncol 103:977–984 Ataseven B, Harter P, Grimm C, Heitz F, Heikaus S, Traut A et al (2016) The revised 2014 FIGO staging system for epithelial ovarian cancer: Is a subclassification into FIGO stage IVA and IVB justified? Gynecol Oncol 142:243–247 Stavros S, Potiris A, Machairiotis N, Fotiou A, Zarogoulidis P, Drakaki E et al (2023) Inguinal lymph node metastasis as sole manifestation of ovarian / fallopian tube cancer: A review of the literature. J Cancer 14:3176–3181 Lopes A, Rangel Costa RL, di Paula R, Anton C, Calheiros Y, Sartorelli V (2019) Cardiophrenic lymph node resection in cytoreduction for primary advanced or recurrent epithelial ovarian carcinoma: a cohort study. Int J Gynecol Cancer 29:188–194 Chalif J, Yao M, Gruner M, Kuznicki M, Vargas R, Rose PG et al (2022) Incidence and prognostic significance of inguinal lymph node metastasis in women with newly diagnosed epithelial ovarian cancer. Gynecol Oncol 165 90–96 Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213 Rosendahl M, Høgdall CK, Mosgaard BJ (2016) Restaging and survival analysis of 4036 ovarian cancer patients according to the 2013 FIGO classification for ovarian, fallopian tube, and primary peritoneal cancer. Int J Gynecol Cancer 26:680–687 Sørensen SM, Høgdall C, Mosgaard BJ, Dalgaard MIR, Jensen MP, Fuglsang K et al (2022) Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer. Acta Obstet Gynecol Scand101:334–343 Kajiyama H, Tamauchi S, Takahashi F, Kawana K (2016) Board members of the 2023 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology. Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2021 and annual treatment report for 2016. J Obstet Gynaecol Res. 2024 Di Giorgio A, Cardi M, Biacchi D, Sibio S, Accarpio F, Ciardi A et al (2013) Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases. World J Surg Oncol 11:64 Gallotta V, Fanfani F, Vizzielli G, Panico G, Rossitto C, Gagliardi ML et al (2011) Douglas peritonectomy compared to recto-sigmoid resection in optimally cytoreduced advanced ovarian cancer patients: analysis of morbidity and oncological outcome. Eur J Surg Oncol 37:1085–1092 Harter P, Mouret-Reynier MA, Pignata S, Cropet C, González-Martín A, Bogner G et al (2022) Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial. Gynecol Oncol 164:254–264 Jochum F, Dumas É, Gougis P, Hamy AS, Querleu D, Lecointre L et al (2025) Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation. Am J Obstet Gynecol 232:194e1–19411 Supplementary Table 1 Supplementary table S1 is not available with this version. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6127970","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":434706622,"identity":"42529960-48a7-4fd8-b95d-4807bfc01fca","order_by":0,"name":"yusuke toyohara","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYJACxgYwxXwASEjIEKvFAEixJYC08JCihQdEMBDWYnAj/ZnkjIo/cgbHez6/ulFjwcPAfvjoBvxacswkN5wxMDY4c3abdc4xoMN40tJuENDCJvmwzSBxw43cbcY5bEAtEjxmBLQAHfbwH0hLzjPjnH9EaUkwk9zYANbC/Di3jQgtkmfeGFvOOGZsLHnmmBlzbp8EDxshv/AdT394s6dGTo7vePPjzznf6uT42Q8fw6tF4QCCwSYBYrDhUw4C8g0IBvMHQqpHwSgYBaNgZAIAR8JNAntZRvYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9417-7496","institution":"The cancer institute hospital of JFCR","correspondingAuthor":true,"prefix":"","firstName":"yusuke","middleName":"","lastName":"toyohara","suffix":""},{"id":434706623,"identity":"ac8fb324-6aea-4025-8f1b-9394ec6293c6","order_by":1,"name":"Atsushi Fusegi","email":"","orcid":"https://orcid.org/0000-0001-6044-2781","institution":"The cancer institute hospital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Atsushi","middleName":"","lastName":"Fusegi","suffix":""},{"id":434706624,"identity":"579379e5-6163-4cbe-bea4-268274a953ff","order_by":2,"name":"Motoko Kanno","email":"","orcid":"","institution":"The cancer institute hospital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Motoko","middleName":"","lastName":"Kanno","suffix":""},{"id":434706625,"identity":"91bd1094-cdfd-40fc-8ca4-c1c2c215ae62","order_by":3,"name":"Sachiho Netsu","email":"","orcid":"","institution":"The cancer institute hospital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Sachiho","middleName":"","lastName":"Netsu","suffix":""},{"id":434706626,"identity":"6e36042e-1b59-4e12-b13f-28ab8c2b9e26","order_by":4,"name":"Terumi Tanigawa","email":"","orcid":"","institution":"The cancer institute hosopital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Terumi","middleName":"","lastName":"Tanigawa","suffix":""},{"id":434706627,"identity":"69fffb82-36f3-4ded-b70d-5782d5f6d9b7","order_by":5,"name":"Mayu Yunokawa","email":"","orcid":"","institution":"The cancer institute hospital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Mayu","middleName":"","lastName":"Yunokawa","suffix":""},{"id":434706628,"identity":"23b1a39a-8b6e-4474-b528-5043f401f8de","order_by":6,"name":"Hiroyuki Kanao","email":"","orcid":"","institution":"The cancer insutitute hospital of JFCR","correspondingAuthor":false,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Kanao","suffix":""}],"badges":[],"createdAt":"2025-02-28 11:07:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6127970/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6127970/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1111/jog.70076","type":"published","date":"2025-09-13T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80023190,"identity":"b611a899-df14-4d71-8678-e339fe68bfc3","added_by":"auto","created_at":"2025-04-07 05:32:13","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":215045,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study population selection process. EOC, epithelial ovarian cancer.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6127970/v1/b73cfcafa1b565106576e72d.jpeg"},{"id":80023181,"identity":"c1de09ff-080b-4892-a0d9-b43e87b68f47","added_by":"auto","created_at":"2025-04-07 05:31:26","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":606179,"visible":true,"origin":"","legend":"\u003cp\u003eA specimen of tumor resection with low anterior resection of the rectum\u003c/p\u003e\n\u003cp\u003eThe dorsal side of the uterus and rectum are illustrated. The yellow arrows indicate the site of bowel mucosal invasion. Scale bar in cm.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6127970/v1/cc688a986cfbf732a29a38e4.jpeg"},{"id":80023180,"identity":"236b6f51-000b-4058-9e26-fd1922a115aa","added_by":"auto","created_at":"2025-04-07 05:31:24","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":154139,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for progression-free survival (PFS; a) and overall survival (OS; b) in patients diagnosed with stage IVB EOC due to bowel mucosal invasion alone.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6127970/v1/389cfd0d210e1a751e0f68ad.jpeg"},{"id":92432243,"identity":"cd61de15-be1c-4ce7-b877-6e84d5998bd8","added_by":"auto","created_at":"2025-09-29 16:21:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1561177,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6127970/v1/b2fa15cf-3546-4573-8855-48ee1a287908.pdf"}],"financialInterests":"","formattedTitle":"Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eEvery year, 300,000 women worldwide are newly diagnosed with epithelial ovarian cancer (EOC) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. EOC is the fifth leading cause of cancer-related death in women [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and the leading cause of death in women with gynecological cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with two-thirds of patients being diagnosed with advanced-stage tumors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition to the use of high-dose surgical cytoreductive and platinum-plus-taxane-based chemotherapy, novel treatment modalities such as bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors have been introduced, leading to improved prognosis. Despite these advances, 5-year overall survival (OS) in advanced EOC has not reached 50% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor advanced-stage EOC, either interval debulking surgery after neoadjuvant chemotherapy (NAC-IDS) or primary debulking surgery (PDS) followed by adjuvant chemotherapy were taken into consideration. In PDS and NAC-IDS, the most important prognostic factor is the absence of residual disease (R0) after surgery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Evidence on the benefit of surgery in stage IVB is limited as most randomized controlled trial analyses for stage IVB are subgroup analyses [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Stage IVB is generally considered to be a systemic condition, and therefore NAC-IDS is often used for Stage IVB since resection of R0 is not considered possible in PDS. The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification (FIGO2014) categorized ovarian cancer with bowel mucosal invasion as stage IVB [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and the reasons for this classification remain unclear. A few studies have reported that bowel mucosal invasion is not a prognostic factor for stage IVB [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]; however, the prognostic effect of bowel mucosal invasion remains uncertain, as the incidence is rare, occurring in approximately 5% of patients with stage IVB EOC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. While the appropriate treatment of Stage IVB is still being considered, there are other resectable sites of disease, such as the cardiophrenic and inguinal lymph nodes, which are classified as stage IVB in FIGO2014 and several studies suggested resection of those lesions are feasible and reconsidering the classification [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similarly, a full resection of stage IVB EOC with bowel mucosal invasion may improve prognosis.\u003c/p\u003e \u003cp\u003eIn this study, we examined EOC cases with bowel mucosal invasion and evaluated the validity of the classification for these events.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eThis study was designed as a retrospective cohort review and included patients with stage IVB FIGO2014 EOC (including epithelial ovarian, fallopian tube, and peritoneal cancer) due to bowel mucosal invasion. Patients were treated at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between January 2011 and September 2023. Both patients with mucosal invasion of the appendix alone and those with bowel mucosal invasion in addition to other characteristics linked to stage IVB EOC, such as parenchymal metastases, were excluded. Pre-treatment diagnosis was based on computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT findings. Board-certified pathologists have obtained histopathological evidence of bowel mucosal invasion from surgical samples or biopsies.\u003c/p\u003e \u003cp\u003eThe surgical procedures were based on disease distribution. According to the surgeon who carried out the procedure, R0 resection was defined as having no residual disease following surgery; if there were residual lesions, the status was classified as nonR0. The Clavien\u0026ndash;Dindo classification was used for the evaluation of post-operative complications, with grade III or higher were being reported [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Chemotherapies, followed by maintenance therapies such as PARP inhibitors or bevacizumab, were administered at the physician\u0026rsquo;s discretion.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEndpoints\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was progression-free survival (PFS), calculated from the end date of primary treatment to the date of diagnosis of progression or recurrence, at the end of last follow-up, or at the end of September 2024, and the secondary endpoint was overall survival (OS), calculated from the date of diagnosis of EOC to the date of death, last follow-up, or September 2024. Recurrence or progression of EOC was diagnosed by imaging or by biopsy. The follow-up period was from the date of diagnosis until the date of death, whichever was the earliest, the last follow-up, or September 2024.\u003c/p\u003e\n\u003ch3\u003ePatient variables\u003c/h3\u003e\n\u003cp\u003eWe evaluated the following variables: age, body mass index (kg/m\u003csup\u003e2\u003c/sup\u003e), cancer type, histopathological type, mucosal invasion site, primary treatment types, surgical procedures, resection status after primary treatment, chemotherapy types and maintenance therapy for first-line treatment, PFS, OS, and recurrence sites. Age, BMI (kg/m2), cancer type, histopathological type, mucosal invasion site, primary treatment types, surgical procedures, resection status following primary treatment, types of chemotherapy and maintenance therapy for first-line treatment, PFS, OS, and recurrence sites were among the variables we assessed.\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eWe estimated OS and PFS for the survival analysis using the Kaplan\u0026ndash;Meier estimator. Statistical analyses were performed in R (version 4.1.2).\u003c/p\u003e\n\u003ch3\u003eEthics\u003c/h3\u003e\n\u003cp\u003e The Institutional Review Board at the Cancer Institute Hospital of Japanese Foundation for Cancer Research approved this study (approval number: 2023-GB-079). Owing to the anonymization of the data, the requirement for informed consent was waived.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eBetween 2011 and 2023, 254 patients in our institutions were diagnosed with stage IVB EOC, 23 of whom were diagnosed with bowel mucosal invasion (9.1%). Thirteen patients were diagnosed with stage IVB EOC based solely on bowel mucosal invasion, and ten patients were assigned to stage IVB based on additional features. Therefore, 5.1% of patients with stage IVB EOC were diagnosed with stage IVB EOC solely on the basis of the bowel mucosal invasion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e lists the patient characteristics. Median duration of follow-up was 40.5 months (range 14.9 to 81.6 months). Ten patients (76.9%) had high-grade serous carcinoma (HGSC), followed by two (15.4%) with clear cell carcinoma, one (7.7%) with endometrioid carcinoma. The most common site of bowel mucosal invasion was the rectum (46.1%), followed by the sigmoid colon (30.8%).\u003c/p\u003e \u003cp\u003eCytoreductive surgery was performed in all patients and PDS in nine patients (69.2%) and NAC-IDS in four (30.8%). R0 resection was achieved in all patients. The surgical procedures are listed in Table S1, and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows an example of a tumor resection with low anterior resection of the rectum. One patient (7.7%) had small intestinal resection, two (15.4%) had transverse colon resection, twelve patients (92.3%) had low anterior resection, and one (7.7%) had ileocecal resection. All patients received adjuvant chemotherapy and four of them (30.8%) received maintenance therapy (two with PARP inhibitor plus bevacizumab, two with PARP inhibitor).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBowel mucosal invasion alone (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, median, years (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (33\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI, median (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.6 (15.5\u0026ndash;23.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003ePrimary site of disease, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOvarian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (61.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFallopian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (15.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeritoneal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHistopathological types, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHGSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (76.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndometrioid carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eSite of mucosal invasion, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (46.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSigmoid colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (30.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTransverse colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCecum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHistory of cytoreductive surgery, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (69.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNAC-IDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (30.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eResidual disease, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBMI, body mass index; HGSC, high-grade serous carcinoma; PDS, primary debulking surgery; NAC-IDS, neoadjuvant chemotherapy and interval debulking surgery.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFive patients (38.5%) had a recurrence of disease and two patients (15.4%) died. The most common metastasis sites were peritoneum (23.1%), followed by liver (15.4%) and lymph nodes (15.4%). Figures\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb illustrate the Kaplan\u0026ndash;Meier plots for PFS and OS. The 3-year PFS and OS rates were 54.9% and 82.1%, respectively. Median PFS and OS were not reached.\u003c/p\u003e \u003cp\u003ePostoperative complications occurred in three patients (23.1%), and no patient died during the perioperative period as a result of postoperative complications. All patients experienced postoperative complications recovered well and all of them could receive subsequent adjuvant chemotherapy.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we investigated the characteristics of stage IVB EOC caused by bowel mucosal invasion. In our cohort, the incidence of stage IVB EOC due to bowel mucosal invasion alone was 5.1%. Due to bowel mucosal invasion alone, we were able to achieve R0 resection in every patient with stage IVB EOC. The 3-year PFS and OS rates were 54.9% and 82.1%, respectively. Previously, the 5-year survival rates and median OS for stage IVB EOC ranged from 11.7\u0026ndash;38% and 23 to 48 months, respectively [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and the 5-year survival rates of stage III EOC were 22 to 54.3% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In our data, the 3- and 5-year PFS and OS rates were similar, and the prognosis in our study for patients with stage IVB EOC due to bowel mucosal was relatively better than that for patients with stage IVB and even stage III EOC, as previously reported. We considered that this might be because R0 resection was achieved in all patients diagnosed with stage IVB EOC due to bowel mucosal invasion alone. Therefore, our data suggested bowel mucosal invasion may not be considered as a factor in the stage IVB EOC.\u003c/p\u003e \u003cp\u003eBowel mucosal invasion did not demonstrate prognostic potential for stage IVB EOC cancer in this investigation. Limited evidence is inconclusive, with some studies supporting bowel mucosal invasion as a prognostic factor and others opposing it (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Giorgio et al. reported that deep bowel invasion is a prognostic factor (5-year survival rates of invasion with serous, muscular, and mucosal layers were 72.7%, 33.1%, and 0%, respectively), supporting the FIGO2014 classification [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. By contrast, Mert et al. reported a longer PFS and OS in the group with bowel invasion of the muscle, submucosal, or mucosal layer than in the group with serosal or subserosal invasion (PFS, 33.5 and 18.2 months; OS, 82.3 and 51.5 months, respectively; not significant). This suggests that a deeper invasion to the bowel is not a prognostic factor of stage IVB disease [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. We concentrated on the prognosis in stage IVB EOC due to bowel mucosal invasion in primary treatment because of the limited evidence, and we think that factors for categorizing bowel mucosal invasion in EOC are crucial.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLiterature review The plus symbols indicate those that support bowel mucosal invasion given the prognostic evidence for stage IVB epithelial ovarian cancer and the minus symbols indicate those that oppose it.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJournal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal number of patients (primary therapy)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of patients with mucosal bowel invasion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMucosal bowel invasion as prognostic factor\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGynecol Oncol.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 \u003c/p\u003e \u003cp\u003eincluding muscularis invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePFS of patients with serosa/subserosa invasion was longer than that of muscularis/mucosa (26 vs 7 months, p\u0026thinsp;=\u0026thinsp;0.176)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEur J Surg Oncol.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDepth of bowel wall invasion was not associated to PFS and OS.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWorld J Surg Oncol.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDepth of bowel wall invasion is associated to 5-year survival (serosal: 72.7%, muscularis: 33.1%, mucosa: 0% p\u0026thinsp;=\u0026thinsp;000.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGynecol Oncol.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003eincluding submucosal invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePFS and OS of patients with muscularis/submucosa/mucosa invasion were longer those of serosal/subserosal invasion (median PFS, 33.5 vs. 18.2 months, p\u0026thinsp;=\u0026thinsp;0.34; median OS, 82.3 vs. 51.5 months, p\u0026thinsp;=\u0026thinsp;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAlthough the prognosis for advanced EOC has improved with PARP inhibitors, the importance of surgical therapy remains because R0 resection is a significant prognostic factor even after the use of pharmacological interventions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In a study of stage IVB EOC, the prognosis of patients who underwent PDS with R0 resection was better than that of the other groups (PDS without R0 resection, NAC-IDS, or chemotherapy only) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Although the EORTC 55971 and CHORUS trials' pooled analysis indicated that NAC-IDS produced favorable outcomes compared with PDS [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], Jochum et al. examined 2772 stage IV EOC patients, and PDS showed better results than NAC-IDS, particularly for patients with extra-abdominal lymph node, supradiaphragm, or pleural metastases. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Because heterogeneity exists among stage IVB EOC, comprehensive studies of the prognostic factors for stage IVB EOC are needed.\u003c/p\u003e \u003cp\u003eThis study had some limitations. First, it was a retrospective single-center, single-arm study with a limited number of patients and follow-up duration. Therefore, various confounding factors, such as \u003cem\u003eBRCA\u003c/em\u003e and homologous recombination status, could not be adjusted for. Second, due to the approval of new treatments such as PARP inhibitors and bevacizumab, treatment modalities have changed between patients. Therefore, long-term prognosis in patients with stage IVB EOC with bowel mucosal invasion should be evaluated after the adoption of the new strategy.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis research focused on the outlook for patients diagnosed with stage IVB EOC caused by bowel mucosal invasion. It was found that R0 resection is a feasible option, and if this is achieved, the prognosis for these patients is more hopeful than the general population diagnosed with stage IVB. Thus, bowel mucosal invasion does not have the potential to be a prognostic factor for stage IVB EOC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAll authors have no competing interests to disclose.\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e \u003cp\u003eYusuke Toyohara: data curation, investigation, formal analyses, methodology, visualization, writing (original draft), writing (review and editing). Atsushi Fusegi: conceptualization, data curation, funding acquisition, methodology, project administration, writing (original draft), writing (review and editing). Motoko Kanno: methodology, supervision, writing (review and editing). Sachiho Netsu: data curation, writing (review and editing). Terumi Tanigawa: methodology, supervision, writing (review and editing). Mayu Yunokawa: methodology, supervision, writing (review and editing). Hiroyuki Kanao: supervision, writing (review and editing).\u003c/p\u003e\u003ch2\u003eACKNOWLEDGMENTS\u003c/h2\u003e \u003cp\u003eThe authors thank Editage for English language editing (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.editage.com/\u003c/span\u003e\u003cspan address=\"https://www.editage.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). No specific funding was provided for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209\u0026ndash;249\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7\u0026ndash;30\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eColombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I et al (2019) ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. ESMO-ESGO Ovarian Cancer Consensus Conference Working Group. Ann Oncol 30:672\u0026ndash;705\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLheureux S, Braunstein M, Oza AM (2019) Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin 69:280\u0026ndash;304\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLiu H, Luo M, Peng C, Huang J, Wang D, Huang J et al (2023) A retrospective analysis for investigating the relationship between FIGO stage IVA/IVB and cytoreductive surgery with prognosis in epithelial ovarian cancer. Front Oncol 13:1103357\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eVergote I, Coens C, Nankivell M, Kristensen GB, Parmar MKB, Ehlen T et al (2018) Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol 19:1680\u0026ndash;1687\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T et al (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 86:249\u0026ndash;257\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eVergote I, Trop\u0026eacute; CG, Amant F, Kristensen GB, Ehlen T, Johnson N et al (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943\u0026ndash;953\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eM\u0026eacute;tairie M, Benoit L, Koual M, Bentivegna E, Wohrer H, Bolze PA et al (2023) A suggested modification to FIGO stage IV epithelial ovarian cancer. Cancers (Basel) 15:706\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMert I, Kumar A, Torres D, Huang Y, McGree ME, Weaver AL et al (2019) Should mucosal bowel invasion in ovarian cancer be assigned to FIGO stage IV disease? Gynecol Oncol153:238\u0026thinsp;\u0026ndash;\u0026thinsp;41\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePark JY, Seo SS, Kang S, Lee KB, Lim SY, Choi HS et al (2006) The benefits of low anterior en bloc resection as part of cytoreductive surgery for advanced primary and recurrent epithelial ovarian cancer patients outweigh morbidity concerns. Gynecol Oncol 103:977\u0026ndash;984\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAtaseven B, Harter P, Grimm C, Heitz F, Heikaus S, Traut A et al (2016) The revised 2014 FIGO staging system for epithelial ovarian cancer: Is a subclassification into FIGO stage IVA and IVB justified? Gynecol Oncol 142:243\u0026ndash;247\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eStavros S, Potiris A, Machairiotis N, Fotiou A, Zarogoulidis P, Drakaki E et al (2023) Inguinal lymph node metastasis as sole manifestation of ovarian / fallopian tube cancer: A review of the literature. J Cancer 14:3176\u0026ndash;3181\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLopes A, Rangel Costa RL, di Paula R, Anton C, Calheiros Y, Sartorelli V (2019) Cardiophrenic lymph node resection in cytoreduction for primary advanced or recurrent epithelial ovarian carcinoma: a cohort study. Int J Gynecol Cancer 29:188\u0026ndash;194\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChalif J, Yao M, Gruner M, Kuznicki M, Vargas R, Rose PG et al (2022) Incidence and prognostic significance of inguinal lymph node metastasis in women with newly diagnosed epithelial ovarian cancer. Gynecol Oncol\u0026nbsp;\u003c/span\u003e\u003cspan\u003e165 90\u0026ndash;96\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205\u0026ndash;213\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRosendahl M, H\u0026oslash;gdall CK, Mosgaard BJ (2016) Restaging and survival analysis of 4036 ovarian cancer patients according to the 2013 FIGO classification for ovarian, fallopian tube, and primary peritoneal cancer. Int J Gynecol Cancer 26:680\u0026ndash;687\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eS\u0026oslash;rensen SM, H\u0026oslash;gdall C, Mosgaard BJ, Dalgaard MIR, Jensen MP, Fuglsang K et al (2022) Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer. Acta Obstet Gynecol Scand101:334\u0026ndash;343\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKajiyama H, Tamauchi S, Takahashi F, Kawana K (2016) Board members of the 2023 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology. Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2021 and annual treatment report for 2016. J Obstet Gynaecol Res. 2024\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDi Giorgio A, Cardi M, Biacchi D, Sibio S, Accarpio F, Ciardi A et al (2013) Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases. World J Surg Oncol 11:64\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGallotta V, Fanfani F, Vizzielli G, Panico G, Rossitto C, Gagliardi ML et al (2011) Douglas peritonectomy compared to recto-sigmoid resection in optimally cytoreduced advanced ovarian cancer patients: analysis of morbidity and oncological outcome. Eur J Surg Oncol 37:1085\u0026ndash;1092\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHarter P, Mouret-Reynier MA, Pignata S, Cropet C, Gonz\u0026aacute;lez-Mart\u0026iacute;n A, Bogner G et al (2022) Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial. Gynecol Oncol 164:254\u0026ndash;264\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eJochum F, Dumas \u0026Eacute;, Gougis P, Hamy AS, Querleu D, Lecointre L et al (2025) Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation. Am J Obstet Gynecol 232:194e1\u0026ndash;19411\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Supplementary Table 1","content":"\u003cp\u003eSupplementary table S1 is not available with this version. \u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"epithelial ovarian cancer, cancer stage, cytoreduction surgical procedures, neoplasm invasiveness, stage IVB","lastPublishedDoi":"10.21203/rs.3.rs-6127970/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6127970/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBowel mucosal invasion epithelial ovarian cancer (EOC) is classified as stage IVB disease. The reason for this classification remains unclear, and clinical data on bowel mucosal invasion in EOC should be investigated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed data from patients with stage IVB EOC who presented at our hospital with bowel mucosal invasion between January 2011 and September 2023. Patients with bowel mucosal invasion and other factors associated with IVB EOC were excluded from the study. The primary and secondary considerations were progression-free survival (PFS) and overall survival (OS), respectively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwo-hundred fifty-four patients were diagnosed with stage IVB EOC. Among these, 23 (9.1%) patients had bowel mucosal invasion, and 13 (5.1%) were diagnosed with stage IVB EOC based on bowel mucosal invasion alone. The median follow-up period was 40.5 months (range, 14.9\u0026ndash;81.6 months). PDS was performed in nine patients (69.2%), NAC-IDS in four (30.8%), and R0 resection was achieved in all of the 13 patients without other stage IVB-related factors. Among those patients, the 3-year PFS and OS rates were 54.9% and 82.1%, respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe have shown that in cases of bowel mucosal invasion, complete resection may be possible and the prognosis of these patients may be better than in the general population at stage IVB. Based on these observations, we believe that bowel mucosal invasion by itself is not a potential prognostic factor for stage IVB ovarian cancer.\u003c/p\u003e","manuscriptTitle":"Clinical characteristics of bowel mucosal invasion in epithelial ovarian cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-07 05:14:25","doi":"10.21203/rs.3.rs-6127970/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":"d58ffd6d-2c6f-4a8f-8209-62e9c97d8c0c","owner":[],"postedDate":"April 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T16:21:13+00:00","versionOfRecord":{"articleIdentity":"rs-6127970","link":"https://doi.org/10.1111/jog.70076","journal":{"identity":"journal-of-obstetrics-and-gynaecology-research","isVorOnly":true,"title":"Journal of Obstetrics and Gynaecology Research"},"publishedOn":"2025-09-13 00:00:00","publishedOnDateReadable":"September 13th, 2025"},"versionCreatedAt":"2025-04-07 05:14:25","video":"","vorDoi":"10.1111/jog.70076","vorDoiUrl":"https://doi.org/10.1111/jog.70076","workflowStages":[]},"version":"v1","identity":"rs-6127970","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6127970","identity":"rs-6127970","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}