A 30-year study of 355 cases with adult-type ovarian granulosa cell tumors in a tertiary center: Clinical features and factors predicting recurrence

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Methods We reviewed patients with pathologically confirmed AGCT treated at a tertiary center between January 1988 and June 2024. Comprehensive data on disease-free survival (DFS), overall survival (OS), recurrence rates, and prognostic factors were analyzed. Results A total of 355 patients were analyzed. With a median follow-up time of 72 months (range 2–435), recurrence occurred in 101 cases (28.4%), with a median time to first recurrence of 67 months (range 2–246). Survival analysis demonstrated 5- and 10-year DFS rates of 86.2% and 75.1%, respectively, and 5- and 10-year OS rates of 100% and 97.5%. Multivariate analysis identified tumor size > 9 cm (odds ratio (OR) = 3.6, p < 0.001), laparoscopic approach (OR = 2.1, p = 0.002), FIGO stages IC–IV (OR = 2.3, p = 0.032), and tumor rupture (OR = 2.5, p = 0.006) as independent predictors of reduced DFS. Conclusions AGCT demonstrates favorable long-term survival, though recurrence remains a significant concern. Poorer DFS is associated with tumor size (> 9 cm), laparoscopic surgery, tumor rupture, and advanced FIGO stage. FIGO stage IC warrant intensified surveillance due to higher recurrence risk. Fertility-sparing surgery might be feasible and safe in early-stage cases, while complete staging surgery and adjuvant chemotherapy fail to affect DFS. Adult granulosa cell tumors Disease-Free Survival Prognostic Factors Figures Figure 1 Figure 9 Background Adult granulosa cell tumors (AGCTs) are rare sex cord-stromal malignancies representing approximately 2–5% of all ovarian cancers [ 1 ], demonstrating an indolent growth pattern and unpredictable recurrence potential despite generally favorable survival outcomes. Clinically, AGCTs present with nonspecific symptoms (abdominal distension, pain, or palpable mass), while abnormal uterine bleeding driven by estrogen hypersecretion frequently serve as a diagnostic clue [ 2 , 3 ]. Hyperestrogenism may induce endometrial pathology ranging from hyperplasia (26–38%) to synchronous carcinoma (2–10%), necessitating comprehensive endometrial evaluation [ 2 , 4 , 5 ]. Surgical resection remains the cornerstone of management, with approach selection depending on disease stage and patient age/fertility status. For early-stage disease, fertility-sparing unilateral salpingo-oophorectomy is often considered in reproductive-aged women [ 6 ], while postmenopausal patients typically undergo radical surgery including hysterectomy with bilateral salpingo-oophorectomy [ 7 ]. Cytoreductive surgery is the most effective treatment for advanced and recurrent cases [ 7 ]. Adjuvant therapies, such as chemotherapy (e.g., platinum-based regimens) or radiotherapy, are reserved for high-risk or recurrent cases, though their efficacy remains debated due to the indolent nature and chemoresistance of tumor [ 8 , 9 ]. Emerging molecular targets show therapeutic promise, particularly VEGF inhibitors [ 10 ], and pathognomonic FOXL2 mutation present in most cases [ 11 , 12 ]. Despite favorable initial 5-year survival rates exceeding 90% for stage I disease [ 1 ], the indolent nature of AGCTs predisposes to late recurrences, occurring up to 20 years post-diagnosis [ 13 ]. Recurrence rates range from 6 to 48% and 50–80% of patients have a mortal course [ 14 ]. Factors such as tumor size and disease stage may influence recurrence risk. The key prognostic factors have been extensively studied, but no consensus has been reached [ 8 ]. This retrospective study aims to analyze clinicopathological characteristics, surgical details and treatment outcomes in AGCT patients, defining the risk factors affecting recurrence and providing evidence-based recommendation of clinical management. Methods Study design The study retrospectively enrolled and evaluated 355 patients with pathologically confirmed AGCT treated at Peking Union Medical College Hospital (PUMCH) from January 1988 to June 2024. Approval was obtained from the ethics committee for the study (No. I-24PJ430). Patients who lost to follow-up after surgery, had concurrent malignancies except endometrial cancer, and had received radiotherapy or chemotherapy previously were excluded from the study. Patients were followed until June 2024 or until death. Clinical features extracted from electronic databases included age, symptoms, serum tumor markers (CA125), tumor size, disease stage, surgical procedures, any adjuvant therapies, disease recurrence, and survival status. Follow-up was conducted via outpatient records supplemented by standardized telephone interviews (Supplementary File 1). Pathological staging was determined according to the International Federation of Gynecology and Obstetrics (FIGO) criteria for ovarian cancers (2014). The FIGO stage was determined through available clinical, radiological and pathological findings. Fertility-sparing surgery (FSS) referred to procedures preserving the uterus and at least partial ovarian tissue, primarily performed in reproductive-age women with FIGO stage I disease. Radical surgery (RS) entailed hysterectomy with bilateral salpingo-oophorectomy as the minimum requirement. Staging surgery was defined as peritoneal washing, omentectomy (or omental biopsy), and biopsy of peritoneal or any suspicious areas. Senior surgeons determined whether to undergo lymphadenectomy simultaneously, and administer postoperative platinum-based chemotherapy in patients exhibiting high/intermediate-risk FIGO stage I disease (large tumor size, tumor rupture, stage IC, poorly differentiated tumor) after surgery. Although chemotherapeutic regimens evolved during the 36-year study period (e.g., increased use of paclitaxel -carboplatin), indications for adjuvant therapy remained consistent. Cytoreductive surgery was conducted in advanced-stage disease. Pathological results for all eligible patients were reviewed and confirmed by two pathologists from the Department of Pathology at PUMCH. After completing primary treatment, patients were monitored every 3 months during the first 2 years, every 6 months for the subsequent 3 years, and annually thereafter. Clinical assessments included physical examination, tumor marker evaluation, and regular abdominopelvic ultrasound or computed tomography (CT) scans. Recurrence was diagnosed when a measurable lesion was captured by imaging during follow-up. The time from the first surgical intervention to the first radiologically-confirmed recurrence or the last follow-up was defined as disease-free survival (DFS). Overall survival (OS) was calculated from the date of initial treatment to either the date of death or the last follow-up. Statistical analysis Statistical analysis was performed using SPSS software (version 25.0; Chicago, IL, USA). Missing data (tumor size: 19.6%; CA125: 15.8%; Capsular status: 1.7%) were addressed via multiple imputation, generating five datasets using regression models with age, FIGO stage, recurrence status, and surgical approach as predictors. Pooled estimates from imputed datasets were utilized in final analyses. Continuous variables were expressed as mean ± standard deviation or median (range), and statistical differences were assessed using the student’s t- and Mann–Whitney U tests. Categorical variables were reported as numbers (percentages), and statistical differences were assessed using the Pearson's chi-squared test. DFS was calculated using the Kaplan-Meier method and compared with the log-rank test. Univariate P-values were corrected for multiplicity within each set of analyses using the Benjamini–Hochberg false discovery rate (FDR) adjustment. Multivariate analysis was conducted by the Cox proportional hazards model within factors that showed statistical significance in univariate analysis. The results presented as odds ratios (OR) with 95% confidence intervals (CIs). A p-value less than 0.05 was considered statistically significant. Results A total of 365 cases of AGCT were initially diagnosed between January 1988 and June 2024. Following histopathological reassessment, five cases were reclassified (1 thecoma, 1 fibrothecoma, 3 Sertoli-Leydig cell tumors) and five excluded due to postoperative loss to follow-up, resulting in 355 analyzable cases. The cohort demonstrated a mean age of 48.2 ± 13.1 years (range 17–81), with 174 patients (49.0%) aged > 47 years. One hundred and eleven patients (31.3%) were asymptomatic and were incidentally diagnosed during investigations. Vaginal bleeding (34.9%) and abdominal distention with/without palpable adnexal mass (19.7%) were the most frequently reported symptoms, followed by abdominal or pelvic pain (14.1%). Mean tumor diameter measured 8.9 ± 5.9 cm (range 1.5–40) and CA125 level elevated in 15.8% (n = 56) (Table 1 ). At the time of initial surgery, the tumor capsule remained intact in 241 patients (67.9%), while capsule rupture (including spontaneous and iatrogenic) occurred in 114 patients (32.1%) (Table 1 ). All patients received primary surgical intervention, with laparoscopic approaches employed in 186 cases (52.4%). FSS was performed in 152 patients (42.8%), and comprehensive staging surgery was completed for 176 cases (49.6%). Lymphadenectomy was performed in 114 patients (32.1%), comprising combined pelvic and para-aortic lymphadenectomy in 54 cases (47.4% of dissected patients) and isolated pelvic lymphadenectomy in 60 cases (52.6%). Omentectomy was performed in 158 (44.5%) patients. Metastatic involvement was identified in one para-aortic lymph node (0.9%) and six omental specimens (4.0%). One hundred and sixty-six patients (46.8%) were classified as stage IA-B, 167 (47%) as stage IC, 11 (3.1%) as stage II, 10 (2.82%) as stage III, and 1 (0.28%) as stage IV. No residual tumor was observed in any patient during the initial surgery (Table 1 ). Table 1 Clinical, surgical, and pathological features of primary diagnosis in patients with AGCT Factors Values Age (years) Mean ± SD Median (range) 48.2 ± 13.1 47 (17,81) ≤ 47 181 (51) >47 174 (49) Tumor size (cm) Mean ± SD Median (range) 8.9 ± 5.9 7.4 (1.5–40.0) ≤ 9 188 (53) >9 167 (47) Symptoms at diagnosis Abnormal uterine bleeding 124 (34.9) Asymptomatic 111 (31.3) Abdominal distention with or without palpable adnexal mass 70 (19.7) Abdominal pain 50 (14.1) Preoperative CA 125 (IU/ml) Normal (0–35) 299 (84.2) Elevated 56 (15.8) FIGO Stage IA-B 166 (46.8) IC 167 (47) II 11 (3.1) III 10 (2.8) IV 1 (0.3) Rupture of cyst N 241 (67.9) Y 114 (32.1) Surgery approach Laparoscopic 186 (52.4) Transabdominal 169 (47.6) Surgery type FSS 152 (42.8) RS 203 (57.2) Staging surgery N 179 (50.4) Y 176 (49.6) Lymphadenectomy Not performed 241 (67.9) Performed 114 (32.1) Omentectomy Not performed 197 (55.5) Performed 158 (44.5) Endometrial pathology Normal endometrium 203 (57.2) Atypia hyperplasia 22 (6.2) Endometrial cancer 5 (1.4) Not preformed 125 (35.2) Adjuvant chemotherapy N 231 (65.1) Y 124 (34.9) Values are presented as number (%) not otherwise specified. FIGO, International Federation of Gynecology and Obstetrics; SD, standard deviation. FSS, fertility-sparing surgery; RS, radical surgery. Adjuvant chemotherapy was administered to 124 patients (34.9%) with stage IC (n = 102) or stage II-IV (n = 22). Of these, 70 patients (56.5%) received Cisplatin, Etoposide and Bleomycin (PEB), while 45 patients (36.3%) underwent Taxane and Carboplatin (TC). The regimen remained undocumented for nine patients (7.2%), three of whom received supplemental radiotherapy. It was observed that adjuvant therapy demonstrated comparable 5-year DFS to observation alone (81.8% vs 83.4%) and was not an independent prognostic factor for DFS, no matter which chemotherapy regimen was used (p = 0.084) (Table 2 ). Table 2 Factors related to DFS in patients with AGCT Univariate Analysis Multivariate Analysis Parameter 5-year DFS DFS % p Value FDR Odds Ratio 95% CI p Value Age at initial diagnosis ≤ 47 years 88.1 0.502 0.5583 > 47 years 84.2 Ovarian tumor size ≤ 9 cm 90.8 < 0.001 9 cm 75 3.578 2.240–5.716 < 0.001 Surgery type FSS 81.4 0.689 0.689 RS 83.9 Surgery staging N 77 0.023 0.038 Y 89.5 Surgery approach Laparoscopic 80.4 0.011 0.028 2.105 1.313–3.375 0.002 Transabdominal 85.3 Rupture of cyst N 90.9 < 0.001 < 0.001 Y 78 2.514 1.295–4.880 0.006 Lymphadenectomy Not performed 77.6 < 0.001 < 0.001 Performed 86.5 Omentectomy Not performed 78.8 0.013 0.029 Performed 88.8 FIGO Stage IA-B 89.2 < 0.001 < 0.001 IC-IV 77.9 2.343 1.075–5.110 0.032 Adjuvant chemotherapy N 83.4 0.011 0.028 Y 81.8 PEB 89.7 0.084 TC 71.6 DFS, disease-free survival; FIGO, International Federation of Gynecology and Obstetrics; FSS, fertility-sparing surgery; RS, radical surgery; PEB, Cisplatin Etoposide Bleomycin; TC, Taxane and Carboplatin; The median follow-up period of the patients was 72 months (range 2–435). During this period, disease recurrence occurred in 101 patients (28.5%), with a median time to first recurrence of 67 months (range 2–246). Nine patients (2.5%) experienced disease-specific mortality. The calculated DFS rates were 86.2% at 5 years and 75.1% at 10 years, while OS rates reached 100% at 5 years and 97.5% at 10 years. In the univariate analysis, ovarian tumor size over 9 cm, laparoscopic approach, rupture of cyst, without staging surgery, lymphadenectomy or omentectomy, advanced FIGO stage, receiving adjuvant chemotherapy were associated with poor DFS. Multivariate analysis demonstrated that tumor size over 9 cm (OR = 3.578, 95% CI = 2.240–5.716, p < 0.001), laparoscopic approach (OR = 2.105, 95% CI = 1.313–3.375, p = 0.002), rupture of cyst (OR = 2.514, 95% CI = 1.295–4.880, p = 0.006) and FIGO stage IC-IV (OR = 2.343, 95% CI = 1.075–5.110, p = 0.032) were found to be independently poor prognostic factors for recurrence (Table 2 and Fig. 1 ). Discussion AGCTs have a low malignant potential with nonspecific symptoms and lack of reliable tumor markers. While demonstrating significantly better prognosis compared to epithelial ovarian carcinomas, these neoplasms exhibit unique recurrence patterns characterized by delayed onset, multifocal presentation, and distant metastases, all of which substantially impact long-term patient quality of life [ 15 ]. Consequently, it is essential to clarify the clinicopathological characteristics and prognostic determinants in AGCT management. In this large-scale single-center retrospective study, we conducted detailed evaluations of 355 histologically confirmed AGCT cases. The majority of patient were diagnosed at early stages of the disease, with a mean tumor size of 8.9 cm at initial presentation. Sun HD et al. [ 16 ] proposed tumors larger than 13.5 cm correlated with increased recurrence. Similarly, our multivariate analysis revealed tumor size exceeding 9 cm had negative effect on the DFS. Larger tumors likely exhibit a prolonged indolent growth period and have existed for an extended duration before detection and diagnosis, which might be the primary reason for the poor prognosis. FSS remains a crucial consideration for patients desiring fertility preservation. Current evidence regarding its oncological safety presents conflicting perspectives. Earlier studies associated conservative approaches with elevated recurrence rates and compromised survival [ 17 – 19 ], whereas recent investigations, including our findings, demonstrated comparable 5-year DFS rates between FSS and RS cohorts for early-stage disease [ 14 , 20 – 22 ]. Our survival analysis revealed no significant difference in recurrence risk between surgical approaches, thereby supporting the feasibility and safety of FSS. The role of surgical staging in presumed early-stage AGCTs remains a subject of intense debate. Current evidence suggests incomplete surgical staging correlates with diminished DFS and elevated recurrence rates [ 20 , 23 ], potentially due to undetected occult metastases and inadequate adjuvant treatment. However, our clinicopathological analysis of 176 cases with staging surgery revealed only one instance of occult metastasis detected incidentally without macroscopic lesions. Besides, staging surgery had no significant effect on the recurrence in the multivariate analysis. This observation aligned with the conclusion of a prior published research, which emphasized complete tumor resection rather than staging surgery as the critical determinant of recurrence prevention [ 16 ]. Similar findings have been widely reported in other studies [ 14 , 24 , 25 ], reinforcing the hypothesis that microscopic tumor burden in AGCT might be rare in early-stage and staging was unnecessary during the initial surgery. Our analysis further identified transabdominal surgical approach as an independent predictor of improved DFS, likely attributable to enhanced operative field visualization that facilitates clear tumor evaluation, achievement of complete resection margins, and minimization of intraoperative tumor dissemination. Gu Y et al.[ 24 ] also proposed that transabdominal surgery could optimize R0 resection and reduce recurrence rates. In AGCT, staging is a definitive prognostic factor associated with recurrence. Karalok et al. [ 6 ] documented 5-year DFS rates of 96% for stage I, 70% for stage III, and 50% for stage IV. Şahin M et al. [ 14 ] reported that the 5-year DFS was 91% for stage I but declined to 13% in stages II–IV. Oktar O et al. [ 26 ] showed a 3.755-fold recurrence risk increase for stage II-IV disease, and Brink GJ et al. [ 25 ] identified stage IC as particularly high-risk. Our cohort showed a 5-year DFS of 80.42% in stage I patients and 54.73% in stage II-IV patients, however, no significant difference in DFS was observed between the two groups (P = 0.209). Notably, when we grouped stage IC into stage II-IV and re-analyzed the impact of staging on DFS, significant differences were observed. Furthermore, our analysis identified tumor rupture as an independent risk factor for diminished DFS. Previous studies had also demonstrated that cyst rupture [ 27 , 28 ] and positive peritoneal cytology [ 29 , 30 ] were associated with worse clinical outcomes and reduced DFS, further reinforcing the clinical evidence for categorizing FIGO stage IC as a high-risk entity despite its early-stage classification. Adjuvant therapy and close clinical surveillance might be considered in patients with FIGO stage IC. Lymph node involvement in primary surgery for AGCT remains exceedingly rare. Existing literature documents a metastasis rate of approximately 3% in regional lymph nodes [ 20 , 31 ], while our study demonstrated an even lower incidence of 0.87% (1/115). Specifically, systematic lymphadenectomy failed to demonstrate therapeutic value in our cohort, showing no significant improvement in DFS or OS while increasing surgical morbidity rates in reported literature as well [ 31 ]. Multivariate analysis further confirmed that neither lymphadenectomy nor omentectomy significantly impacted recurrence. The lymph node recurrence rate was reported between 0–15% [ 14 , 32 , 33 ], which was 2% in our study (2/101), enhancing current recommendations for targeted resection of suspicious nodes rather than routine lymph node dissection. In the NCCN guidelines, observation or platinum-based adjuvant chemotherapy is recommended for early-stage patients with intermediate-risk factors (heterologous elements) or high-risk factors (ruptured stage IC or poorly differentiated stage I), while adjuvant chemotherapy is particularly suggested for advanced-stage and macroscopically visible residual disease [ 8 , 23 , 34 ]. Nevertheless, the value of postoperative adjuvant chemotherapy remains unclear. In patients receiving adjuvant chemotherapy, neither improvement of DFS in FIGO stage IC cases [ 22 ] nor survival advantages across all stages was reported according to recent meta-analyses and retrospective studies [ 14 , 26 , 35 , 36 ]. Our data similarly revealed no association between adjuvant chemotherapy and enhanced DFS. The BEP regimen remains the preferred protocol for advanced/recurrent cases [ 7 ], and the TC regimen serves as a less toxic alternative to BEP. Our experience and existing literatures suggested the two chemotherapy regimens exhibited comparable efficacy [ 14 , 37 ]. The retrospective nature of this analysis introduces potential selected bias, however, our investigation represents one of the largest AGCT cohorts (n = 355) with extended follow-up (median 72 months), enhancing our capacity to identify recurrence patterns and prognostic determinants. These results contribute substantially to the evolving understanding of this rare low-grade malignant. Conclusions In AGCT, larger tumor size, laparoscopic approach, advanced FIGO stages (IC-IV), and tumor rupture had emerged as significant predictors of adverse DFS. FSS represented a safe therapeutic alternative for reproductive-aged patients with early-stage disease, while RS and staging surgery failed to improve DFS. Lymphadenectomy is not mandatory during the initial surgery. Whether to administer chemotherapy and selection of specific chemotherapeutic protocols did not influence DFS. Declarations Author affiliations Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China. Contributors Gan JW have substantially contributed to the design and writing of the manuscript and data collection. Gan JW, Ma X and Cao Y were responsible for data processing and analysis. Cao DY accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish as a guarantor. Cao DY, Zhou HM, Yu M, Wang T, Zhang Y, Cheng NH, Peng P, Yang JX, Huang HF and Shen K provided cases and confirmed the completeness and accuracy of the data and analyses, and the final approval of the version to be published. Funding This work was supported by the National Key Technology Research and Developmental Program of China (Program Nos. 2022YFC2704400 and 2022YFC2704405). Competing interests The authors declare no competing interests. Ethics approval This study involves human participants and was approved by the Institutional Review Board of Peking Union Medical College Hospital (No. I-24PJ430). The requirement for written informed consent was waived because (a) The Declaration of Helsinki guidelines for retrospective studies using anonymized data, and (b) Chinese national regulations (Regulations on the Management of Human Genetic Resources, Article 24; Ethical Review Measures for Life Science and Medical Research, Article 39). Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement The datasets are not publicly available due to privacy reasons but are available from the corresponding author ( [email protected] ) on reasonable request. 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Abu-Rustum NR, Restivo A, Ivy J, Soslow R, Sabbatini P, Sonoda Y, et al. Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the ovary. Gynecol Oncol. 2006;103:31-4. 10.1016/j.ygyno.2006.01.050. Brown J, Sood AK, Deavers MT, Milojevic L, Gershenson DM. Patterns of metastasis in sex cord-stromal tumors of the ovary: can routine staging lymphadenectomy be omitted? Gynecol Oncol. 2009;113:86-90. 10.1016/j.ygyno.2008.12.007. Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016;62:132-7. 10.1016/j.ejca.2016.03.081. van Meurs HS, Buist MR, Westermann AM, Sonke GS, Kenter GG, van der Velden J. Effectiveness of chemotherapy in measurable granulosa cell tumors: a retrospective study and review of literature. Int J Gynecol Cancer. 2014;24:496-505. 10.1097/igc.0000000000000077. Lee IH, Choi CH, Hong DG, Song JY, Kim YJ, Kim KT, et al. Clinicopathologic characteristics of granulosa cell tumors of the ovary: a multicenter retrospective study. J Gynecol Oncol. 2011;22:188-95. 10.3802/jgo.2011.22.3.188. Mousavi A, Eshraghi N, Akhavan S, Sheikhhasani S, Zamani N, Valian Z, et al. Clinical features and survival rate of patients with ovarian granulosa cell tumor in Iran; a 10-year retrospective study. BMC cancer. 2024;24:1318. 10.1186/s12885-024-13069-w. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile1EnglishVersionoftheAGCTPatientsInterviewGuide.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 18 Sep, 2025 Reviewers agreed at journal 12 Sep, 2025 Reviewers invited by journal 04 Sep, 2025 Editor assigned by journal 03 Sep, 2025 Editor invited by journal 18 Aug, 2025 Submission checks completed at journal 17 Aug, 2025 First submitted to journal 17 Aug, 2025 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. 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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-7329250","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":512856001,"identity":"069a658f-b4f3-4bb6-8acc-d4f6d0b28e5c","order_by":0,"name":"Jingwen Gan","email":"","orcid":"","institution":"National Clinical Research Center for Obstetric \u0026 Gynecologic Diseases, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College, Peking Union Medical College Hospital (Dongdan 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Campus)","correspondingAuthor":false,"prefix":"","firstName":"P","middleName":"","lastName":"Peng","suffix":""},{"id":512856013,"identity":"302b31c7-0e83-42c0-bb4d-75565029377c","order_by":10,"name":"Jiaxin Yang","email":"","orcid":"","institution":"National Clinical Research Center for Obstetric \u0026 Gynecologic Diseases, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)","correspondingAuthor":false,"prefix":"","firstName":"Jiaxin","middleName":"","lastName":"Yang","suffix":""},{"id":512856014,"identity":"e1919152-41ce-4d8a-a0c3-805c213fca0c","order_by":11,"name":"Huifang Huang","email":"","orcid":"","institution":"National Clinical Research Center for Obstetric \u0026 Gynecologic Diseases, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)","correspondingAuthor":false,"prefix":"","firstName":"Huifang","middleName":"","lastName":"Huang","suffix":""},{"id":512856015,"identity":"8bb949ff-e1e0-4426-a02b-753d98049082","order_by":12,"name":"Keng Shen","email":"","orcid":"","institution":"National Clinical Research Center for Obstetric \u0026 Gynecologic Diseases, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)","correspondingAuthor":false,"prefix":"","firstName":"Keng","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2025-08-08 17:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7329250/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7329250/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91085034,"identity":"90032b4a-77de-4ae4-ae30-f15940ec2ca0","added_by":"auto","created_at":"2025-09-11 12:18:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":312225,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier curves for the DFS. (A) DFS according to tumor size. (B) DFS according to surgery approach. (C) DFS according to rupture of cyst. (D) DFS according to FIGO stage.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7329250/v1/63addeaaa6a8c6bb57afa197.png"},{"id":91086615,"identity":"d5a6fd36-864a-4d0c-bbc9-238ede8f2358","added_by":"auto","created_at":"2025-09-11 12:26:52","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":312225,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier curves for the DFS. (A) DFS according to tumor size. (B) DFS according to surgery approach. (C) DFS according to rupture of cyst. (D) DFS according to FIGO stage.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7329250/v1/b8bc427b845c92a3f7e3fefc.png"},{"id":91088562,"identity":"d684d35c-fd81-4164-8edd-c45a4bcf3060","added_by":"auto","created_at":"2025-09-11 12:42:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1714768,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7329250/v1/c9497b73-11ae-457a-ab99-956ab2867aa0.pdf"},{"id":91085031,"identity":"56c402eb-5e51-4b0c-939e-d84af136ecfe","added_by":"auto","created_at":"2025-09-11 12:18:52","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10997,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile1EnglishVersionoftheAGCTPatientsInterviewGuide.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7329250/v1/b7c08740debd59b2dd083b6c.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A 30-year study of 355 cases with adult-type ovarian granulosa cell tumors in a tertiary center: Clinical features and factors predicting recurrence","fulltext":[{"header":"Background","content":"\u003cp\u003eAdult granulosa cell tumors (AGCTs) are rare sex cord-stromal malignancies representing approximately 2\u0026ndash;5% of all ovarian cancers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], demonstrating an indolent growth pattern and unpredictable recurrence potential despite generally favorable survival outcomes.\u003c/p\u003e\u003cp\u003eClinically, AGCTs present with nonspecific symptoms (abdominal distension, pain, or palpable mass), while abnormal uterine bleeding driven by estrogen hypersecretion frequently serve as a diagnostic clue [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Hyperestrogenism may induce endometrial pathology ranging from hyperplasia (26\u0026ndash;38%) to synchronous carcinoma (2\u0026ndash;10%), necessitating comprehensive endometrial evaluation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSurgical resection remains the cornerstone of management, with approach selection depending on disease stage and patient age/fertility status. For early-stage disease, fertility-sparing unilateral salpingo-oophorectomy is often considered in reproductive-aged women [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], while postmenopausal patients typically undergo radical surgery including hysterectomy with bilateral salpingo-oophorectomy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Cytoreductive surgery is the most effective treatment for advanced and recurrent cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Adjuvant therapies, such as chemotherapy (e.g., platinum-based regimens) or radiotherapy, are reserved for high-risk or recurrent cases, though their efficacy remains debated due to the indolent nature and chemoresistance of tumor [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Emerging molecular targets show therapeutic promise, particularly VEGF inhibitors [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and pathognomonic FOXL2 mutation present in most cases [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite favorable initial 5-year survival rates exceeding 90% for stage I disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the indolent nature of AGCTs predisposes to late recurrences, occurring up to 20 years post-diagnosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recurrence rates range from 6 to 48% and 50\u0026ndash;80% of patients have a mortal course [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Factors such as tumor size and disease stage may influence recurrence risk. The key prognostic factors have been extensively studied, but no consensus has been reached [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis retrospective study aims to analyze clinicopathological characteristics, surgical details and treatment outcomes in AGCT patients, defining the risk factors affecting recurrence and providing evidence-based recommendation of clinical management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThe study retrospectively enrolled and evaluated 355 patients with pathologically confirmed AGCT treated at Peking Union Medical College Hospital (PUMCH) from January 1988 to June 2024. Approval was obtained from the ethics committee for the study (No. I-24PJ430). Patients who lost to follow-up after surgery, had concurrent malignancies except endometrial cancer, and had received radiotherapy or chemotherapy previously were excluded from the study. Patients were followed until June 2024 or until death.\u003c/p\u003e\u003cp\u003eClinical features extracted from electronic databases included age, symptoms, serum tumor markers (CA125), tumor size, disease stage, surgical procedures, any adjuvant therapies, disease recurrence, and survival status. Follow-up was conducted via outpatient records supplemented by standardized telephone interviews (Supplementary File 1).\u003c/p\u003e\u003cp\u003ePathological staging was determined according to the International Federation of Gynecology and Obstetrics (FIGO) criteria for ovarian cancers (2014). The FIGO stage was determined through available clinical, radiological and pathological findings. Fertility-sparing surgery (FSS) referred to procedures preserving the uterus and at least partial ovarian tissue, primarily performed in reproductive-age women with FIGO stage I disease. Radical surgery (RS) entailed hysterectomy with bilateral salpingo-oophorectomy as the minimum requirement. Staging surgery was defined as peritoneal washing, omentectomy (or omental biopsy), and biopsy of peritoneal or any suspicious areas. Senior surgeons determined whether to undergo lymphadenectomy simultaneously, and administer postoperative platinum-based chemotherapy in patients exhibiting high/intermediate-risk FIGO stage I disease (large tumor size, tumor rupture, stage IC, poorly differentiated tumor) after surgery. Although chemotherapeutic regimens evolved during the 36-year study period (e.g., increased use of paclitaxel -carboplatin), indications for adjuvant therapy remained consistent. Cytoreductive surgery was conducted in advanced-stage disease. Pathological results for all eligible patients were reviewed and confirmed by two pathologists from the Department of Pathology at PUMCH.\u003c/p\u003e\u003cp\u003eAfter completing primary treatment, patients were monitored every 3 months during the first 2 years, every 6 months for the subsequent 3 years, and annually thereafter. Clinical assessments included physical examination, tumor marker evaluation, and regular abdominopelvic ultrasound or computed tomography (CT) scans. Recurrence was diagnosed when a measurable lesion was captured by imaging during follow-up.\u003c/p\u003e\u003cp\u003eThe time from the first surgical intervention to the first radiologically-confirmed recurrence or the last follow-up was defined as disease-free survival (DFS). Overall survival (OS) was calculated from the date of initial treatment to either the date of death or the last follow-up.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS software (version 25.0; Chicago, IL, USA). Missing data (tumor size: 19.6%; CA125: 15.8%; Capsular status: 1.7%) were addressed via multiple imputation, generating five datasets using regression models with age, FIGO stage, recurrence status, and surgical approach as predictors. Pooled estimates from imputed datasets were utilized in final analyses. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (range), and statistical differences were assessed using the student\u0026rsquo;s t- and Mann\u0026ndash;Whitney U tests. Categorical variables were reported as numbers (percentages), and statistical differences were assessed using the Pearson's chi-squared test. DFS was calculated using the Kaplan-Meier method and compared with the log-rank test. Univariate P-values were corrected for multiplicity within each set of analyses using the Benjamini\u0026ndash;Hochberg false discovery rate (FDR) adjustment. Multivariate analysis was conducted by the Cox proportional hazards model within factors that showed statistical significance in univariate analysis. The results presented as odds ratios (OR) with 95% confidence intervals (CIs). A p-value less than 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 365 cases of AGCT were initially diagnosed between January 1988 and June 2024. Following histopathological reassessment, five cases were reclassified (1 thecoma, 1 fibrothecoma, 3 Sertoli-Leydig cell tumors) and five excluded due to postoperative loss to follow-up, resulting in 355 analyzable cases.\u003c/p\u003e\u003cp\u003eThe cohort demonstrated a mean age of 48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 years (range 17\u0026ndash;81), with 174 patients (49.0%) aged\u0026thinsp;\u0026gt;\u0026thinsp;47 years. One hundred and eleven patients (31.3%) were asymptomatic and were incidentally diagnosed during investigations. Vaginal bleeding (34.9%) and abdominal distention with/without palpable adnexal mass (19.7%) were the most frequently reported symptoms, followed by abdominal or pelvic pain (14.1%). Mean tumor diameter measured 8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 cm (range 1.5\u0026ndash;40) and CA125 level elevated in 15.8% (n\u0026thinsp;=\u0026thinsp;56) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At the time of initial surgery, the tumor capsule remained intact in 241 patients (67.9%), while capsule rupture (including spontaneous and iatrogenic) occurred in 114 patients (32.1%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAll patients received primary surgical intervention, with laparoscopic approaches employed in 186 cases (52.4%). FSS was performed in 152 patients (42.8%), and comprehensive staging surgery was completed for 176 cases (49.6%). Lymphadenectomy was performed in 114 patients (32.1%), comprising combined pelvic and para-aortic lymphadenectomy in 54 cases (47.4% of dissected patients) and isolated pelvic lymphadenectomy in 60 cases (52.6%). Omentectomy was performed in 158 (44.5%) patients. Metastatic involvement was identified in one para-aortic lymph node (0.9%) and six omental specimens (4.0%). One hundred and sixty-six patients (46.8%) were classified as stage IA-B, 167 (47%) as stage IC, 11 (3.1%) as stage II, 10 (2.82%) as stage III, and 1 (0.28%) as stage IV. No residual tumor was observed in any patient during the initial surgery (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eClinical, surgical, and pathological features of primary diagnosis in patients with AGCT\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValues\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eMedian (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e\u003cp\u003e47 (17,81)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e181 (51)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e174 (49)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor size (cm)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003cp\u003eMedian (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003cp\u003e7.4 (1.5\u0026ndash;40.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e188 (53)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e167 (47)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSymptoms at diagnosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbnormal uterine bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e124 (34.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsymptomatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e111 (31.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal distention with or without palpable adnexal mass\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 (19.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (14.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative CA 125 (IU/ml)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal (0\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e299 (84.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (15.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFIGO Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIA-B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e166 (46.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e167 (47)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (3.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (2.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRupture of cyst\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e241 (67.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e114 (32.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgery approach\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaparoscopic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e186 (52.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTransabdominal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e169 (47.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgery type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152 (42.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e203 (57.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStaging surgery\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e179 (50.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e176 (49.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphadenectomy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e241 (67.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e114 (32.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOmentectomy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e197 (55.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e158 (44.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEndometrial pathology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormal endometrium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e203 (57.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAtypia hyperplasia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (6.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndometrial cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot preformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125 (35.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdjuvant chemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e231 (65.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e124 (34.9)\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\u003eValues are presented as number (%) not otherwise specified. FIGO, International Federation of Gynecology and Obstetrics; SD, standard deviation. FSS, fertility-sparing surgery; RS, radical surgery.\u003c/p\u003e\u003cp\u003eAdjuvant chemotherapy was administered to 124 patients (34.9%) with stage IC (n\u0026thinsp;=\u0026thinsp;102) or stage II-IV (n\u0026thinsp;=\u0026thinsp;22). Of these, 70 patients (56.5%) received Cisplatin, Etoposide and Bleomycin (PEB), while 45 patients (36.3%) underwent Taxane and Carboplatin (TC). The regimen remained undocumented for nine patients (7.2%), three of whom received supplemental radiotherapy. It was observed that adjuvant therapy demonstrated comparable 5-year DFS to observation alone (81.8% vs 83.4%) and was not an independent prognostic factor for DFS, no matter which chemotherapy regimen was used (p\u0026thinsp;=\u0026thinsp;0.084) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eFactors related to DFS in patients with AGCT\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eUnivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eMultivariate Analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e5-year DFS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eDFS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep Value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFDR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eOdds Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ep Value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at initial diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;47 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.502\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.5583\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;47 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOvarian tumor size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;9 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;9 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.578\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.240\u0026ndash;5.716\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.689\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.689\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery staging\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery approach\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLaparoscopic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.105\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.313\u0026ndash;3.375\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTransabdominal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e85.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRupture of cyst\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.514\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.295\u0026ndash;4.880\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphadenectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOmentectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFIGO Stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIA-B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIC-IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.343\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.075\u0026ndash;5.110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdjuvant chemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePEB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDFS, disease-free survival; FIGO, International Federation of Gynecology and Obstetrics; FSS, fertility-sparing surgery; RS, radical surgery; PEB, Cisplatin Etoposide Bleomycin; TC, Taxane and Carboplatin;\u003c/p\u003e\u003cp\u003eThe median follow-up period of the patients was 72 months (range 2\u0026ndash;435). During this period, disease recurrence occurred in 101 patients (28.5%), with a median time to first recurrence of 67 months (range 2\u0026ndash;246). Nine patients (2.5%) experienced disease-specific mortality. The calculated DFS rates were 86.2% at 5 years and 75.1% at 10 years, while OS rates reached 100% at 5 years and 97.5% at 10 years.\u003c/p\u003e\u003cp\u003eIn the univariate analysis, ovarian tumor size over 9 cm, laparoscopic approach, rupture of cyst, without staging surgery, lymphadenectomy or omentectomy, advanced FIGO stage, receiving adjuvant chemotherapy were associated with poor DFS. Multivariate analysis demonstrated that tumor size over 9 cm (OR\u0026thinsp;=\u0026thinsp;3.578, 95% CI\u0026thinsp;=\u0026thinsp;2.240\u0026ndash;5.716, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), laparoscopic approach (OR\u0026thinsp;=\u0026thinsp;2.105, 95% CI\u0026thinsp;=\u0026thinsp;1.313\u0026ndash;3.375, p\u0026thinsp;=\u0026thinsp;0.002), rupture of cyst (OR\u0026thinsp;=\u0026thinsp;2.514, 95% CI\u0026thinsp;=\u0026thinsp;1.295\u0026ndash;4.880, p\u0026thinsp;=\u0026thinsp;0.006) and FIGO stage IC-IV (OR\u0026thinsp;=\u0026thinsp;2.343, 95% CI\u0026thinsp;=\u0026thinsp;1.075\u0026ndash;5.110, p\u0026thinsp;=\u0026thinsp;0.032) were found to be independently poor prognostic factors for recurrence (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAGCTs have a low malignant potential with nonspecific symptoms and lack of reliable tumor markers. While demonstrating significantly better prognosis compared to epithelial ovarian carcinomas, these neoplasms exhibit unique recurrence patterns characterized by delayed onset, multifocal presentation, and distant metastases, all of which substantially impact long-term patient quality of life [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Consequently, it is essential to clarify the clinicopathological characteristics and prognostic determinants in AGCT management. In this large-scale single-center retrospective study, we conducted detailed evaluations of 355 histologically confirmed AGCT cases.\u003c/p\u003e\u003cp\u003eThe majority of patient were diagnosed at early stages of the disease, with a mean tumor size of 8.9 cm at initial presentation. Sun HD et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] proposed tumors larger than 13.5 cm correlated with increased recurrence. Similarly, our multivariate analysis revealed tumor size exceeding 9 cm had negative effect on the DFS. Larger tumors likely exhibit a prolonged indolent growth period and have existed for an extended duration before detection and diagnosis, which might be the primary reason for the poor prognosis.\u003c/p\u003e\u003cp\u003eFSS remains a crucial consideration for patients desiring fertility preservation. Current evidence regarding its oncological safety presents conflicting perspectives. Earlier studies associated conservative approaches with elevated recurrence rates and compromised survival [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], whereas recent investigations, including our findings, demonstrated comparable 5-year DFS rates between FSS and RS cohorts for early-stage disease [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our survival analysis revealed no significant difference in recurrence risk between surgical approaches, thereby supporting the feasibility and safety of FSS.\u003c/p\u003e\u003cp\u003eThe role of surgical staging in presumed early-stage AGCTs remains a subject of intense debate. Current evidence suggests incomplete surgical staging correlates with diminished DFS and elevated recurrence rates [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], potentially due to undetected occult metastases and inadequate adjuvant treatment. However, our clinicopathological analysis of 176 cases with staging surgery revealed only one instance of occult metastasis detected incidentally without macroscopic lesions. Besides, staging surgery had no significant effect on the recurrence in the multivariate analysis. This observation aligned with the conclusion of a prior published research, which emphasized complete tumor resection rather than staging surgery as the critical determinant of recurrence prevention [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similar findings have been widely reported in other studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], reinforcing the hypothesis that microscopic tumor burden in AGCT might be rare in early-stage and staging was unnecessary during the initial surgery. Our analysis further identified transabdominal surgical approach as an independent predictor of improved DFS, likely attributable to enhanced operative field visualization that facilitates clear tumor evaluation, achievement of complete resection margins, and minimization of intraoperative tumor dissemination. Gu Y et al.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] also proposed that transabdominal surgery could optimize R0 resection and reduce recurrence rates.\u003c/p\u003e\u003cp\u003eIn AGCT, staging is a definitive prognostic factor associated with recurrence. Karalok et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] documented 5-year DFS rates of 96% for stage I, 70% for stage III, and 50% for stage IV. Şahin M et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] reported that the 5-year DFS was 91% for stage I but declined to 13% in stages II\u0026ndash;IV. Oktar O et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] showed a 3.755-fold recurrence risk increase for stage II-IV disease, and Brink GJ et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] identified stage IC as particularly high-risk. Our cohort showed a 5-year DFS of 80.42% in stage I patients and 54.73% in stage II-IV patients, however, no significant difference in DFS was observed between the two groups (P\u0026thinsp;=\u0026thinsp;0.209). Notably, when we grouped stage IC into stage II-IV and re-analyzed the impact of staging on DFS, significant differences were observed. Furthermore, our analysis identified tumor rupture as an independent risk factor for diminished DFS. Previous studies had also demonstrated that cyst rupture [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and positive peritoneal cytology [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] were associated with worse clinical outcomes and reduced DFS, further reinforcing the clinical evidence for categorizing FIGO stage IC as a high-risk entity despite its early-stage classification. Adjuvant therapy and close clinical surveillance might be considered in patients with FIGO stage IC.\u003c/p\u003e\u003cp\u003eLymph node involvement in primary surgery for AGCT remains exceedingly rare. Existing literature documents a metastasis rate of approximately 3% in regional lymph nodes [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], while our study demonstrated an even lower incidence of 0.87% (1/115). Specifically, systematic lymphadenectomy failed to demonstrate therapeutic value in our cohort, showing no significant improvement in DFS or OS while increasing surgical morbidity rates in reported literature as well [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Multivariate analysis further confirmed that neither lymphadenectomy nor omentectomy significantly impacted recurrence. The lymph node recurrence rate was reported between 0\u0026ndash;15% [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], which was 2% in our study (2/101), enhancing current recommendations for targeted resection of suspicious nodes rather than routine lymph node dissection.\u003c/p\u003e\u003cp\u003eIn the NCCN guidelines, observation or platinum-based adjuvant chemotherapy is recommended for early-stage patients with intermediate-risk factors (heterologous elements) or high-risk factors (ruptured stage IC or poorly differentiated stage I), while adjuvant chemotherapy is particularly suggested for advanced-stage and macroscopically visible residual disease [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Nevertheless, the value of postoperative adjuvant chemotherapy remains unclear. In patients receiving adjuvant chemotherapy, neither improvement of DFS in FIGO stage IC cases [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] nor survival advantages across all stages was reported according to recent meta-analyses and retrospective studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Our data similarly revealed no association between adjuvant chemotherapy and enhanced DFS. The BEP regimen remains the preferred protocol for advanced/recurrent cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and the TC regimen serves as a less toxic alternative to BEP. Our experience and existing literatures suggested the two chemotherapy regimens exhibited comparable efficacy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe retrospective nature of this analysis introduces potential selected bias, however, our investigation represents one of the largest AGCT cohorts (n\u0026thinsp;=\u0026thinsp;355) with extended follow-up (median 72 months), enhancing our capacity to identify recurrence patterns and prognostic determinants. These results contribute substantially to the evolving understanding of this rare low-grade malignant.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn AGCT, larger tumor size, laparoscopic approach, advanced FIGO stages (IC-IV), and tumor rupture had emerged as significant predictors of adverse DFS. FSS represented a safe therapeutic alternative for reproductive-aged patients with early-stage disease, while RS and staging surgery failed to improve DFS. Lymphadenectomy is not mandatory during the initial surgery. Whether to administer chemotherapy and selection of specific chemotherapeutic protocols did not influence DFS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor affiliations\u003c/strong\u003e Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026amp; Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e Gan JW have substantially contributed to the design and writing of the manuscript and data collection. Gan JW, Ma X and Cao Y were responsible for data processing and analysis. Cao DY accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish as a guarantor.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCao DY, Zhou HM, Yu M, Wang T, Zhang Y, Cheng NH, Peng P, Yang JX, Huang HF and Shen K provided cases and confirmed the completeness and accuracy of the data and analyses, and the final approval of the version to be published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis work was supported by the National Key Technology Research and Developmental Program of China (Program Nos. 2022YFC2704400 and 2022YFC2704405).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e This study involves human participants and was approved by the Institutional Review Board of Peking Union Medical College Hospital (No. I-24PJ430). The requirement for written informed consent was waived because (a) The Declaration of Helsinki guidelines for retrospective studies using anonymized data, and (b) Chinese national regulations (Regulations on the Management of Human Genetic Resources, Article 24; Ethical Review Measures for Life Science and Medical Research, Article 39).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProvenance and peer review\u003c/strong\u003e Not commissioned; externally peer reviewed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e The datasets are not publicly available due to privacy reasons but are available from the corresponding author ([email protected]) on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchumer ST, Cannistra SA. Granulosa cell tumor of the ovary. J Clin Oncol. 2003;21:1180-9. 10.1200/jco.2003.10.019.\u003c/li\u003e\n\u003cli\u003eGusberg SB, Kardon P. 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BMC cancer. 2024;24:1318. 10.1186/s12885-024-13069-w.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adult granulosa cell tumors, Disease-Free Survival, Prognostic Factors","lastPublishedDoi":"10.21203/rs.3.rs-7329250/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7329250/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThis retrospective study aims to evaluate the clinicopathological features of adult granulosa cell tumors (AGCT) and identify prognostic factors influencing disease recurrence.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e We reviewed patients with pathologically confirmed AGCT treated at a tertiary center between January 1988 and June 2024. Comprehensive data on disease-free survival (DFS), overall survival (OS), recurrence rates, and prognostic factors were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 355 patients were analyzed. With a median follow-up time of 72 months (range 2\u0026ndash;435), recurrence occurred in 101 cases (28.4%), with a median time to first recurrence of 67 months (range 2\u0026ndash;246). Survival analysis demonstrated 5- and 10-year DFS rates of 86.2% and 75.1%, respectively, and 5- and 10-year OS rates of 100% and 97.5%. Multivariate analysis identified tumor size\u0026thinsp;\u0026gt;\u0026thinsp;9 cm (odds ratio (OR)\u0026thinsp;=\u0026thinsp;3.6, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), laparoscopic approach (OR\u0026thinsp;=\u0026thinsp;2.1, p\u0026thinsp;=\u0026thinsp;0.002), FIGO stages IC\u0026ndash;IV (OR\u0026thinsp;=\u0026thinsp;2.3, p\u0026thinsp;=\u0026thinsp;0.032), and tumor rupture (OR\u0026thinsp;=\u0026thinsp;2.5, p\u0026thinsp;=\u0026thinsp;0.006) as independent predictors of reduced DFS.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eAGCT demonstrates favorable long-term survival, though recurrence remains a significant concern. Poorer DFS is associated with tumor size (\u0026gt;\u0026thinsp;9 cm), laparoscopic surgery, tumor rupture, and advanced FIGO stage. FIGO stage IC warrant intensified surveillance due to higher recurrence risk. Fertility-sparing surgery might be feasible and safe in early-stage cases, while complete staging surgery and adjuvant chemotherapy fail to affect DFS.\u003c/p\u003e","manuscriptTitle":"A 30-year study of 355 cases with adult-type ovarian granulosa cell tumors in a tertiary center: Clinical features and factors predicting recurrence","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 12:18:48","doi":"10.21203/rs.3.rs-7329250/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-09-18T14:39:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117466429954298512908086322864569050306","date":"2025-09-12T10:00:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-04T15:17:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-03T06:35:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-18T10:21:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-17T16:11:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-08-17T16:08:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"33c7c478-59ee-4f22-b845-a8c8129b3b6d","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-11T12:18:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 12:18:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7329250","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7329250","identity":"rs-7329250","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}