Purpose: Considering the current lack of consensus on post–poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment. Materials and Methods: This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence. Results: Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8, and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine+carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.019). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities. Conclusion In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine+carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

Objective: To evaluate upstaging, lymph node (LN) metastasis, and recurrence in patients with presumed stage I endometrial cancer using preoperative magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT). Methods: Retrospective review of 422 patients with presumed clinical stage I endometrial cancer diagnosed via MRI and PET-CT (July 2014–June 2023). Surgical staging included pelvic lymph nodes (PLNs) and para-aortic lymph nodes (PALNs), classifying patients as low/ intermediate- or high-risk groups. Results: Post-operative upstaging rate was 14.5% (8.8% low/intermediate-risk vs. 22.8% high-risk, p<0.001). LN metastasis occurred in 5.5% of patients (2.0% low/intermediaterisk vs. 10.5% high-risk, p<0.001), with a dual imaging negative predictive value of 0.945.PLN metastasis was 4.5% (2.0% low/intermediate vs. 8.2% high-risk, p=0.003), and PALN metastasis was 2.6% (0.4% low/intermediate-risk vs. 5.8% high-risk, p=0.001). In low/ intermediate-risk group: tumors ≤2cm had 1.1% LN metastasis rate, endometrium-limited 0.8%, and ≤2cm with endometrium-limited 0.9%. Deep myometrial invasion (odds ratio [OR]=4.4; 95% confidence intervals [CIs]=1.6–12.4) and tumor size >2 cm on MRI (OR=2.9;95% CI=0.8–9.9) increased LN metastasis risk. Median 48.5-month follow-up showed an 8.1% overall recurrence rate (4.0% low/intermediate-risk vs. 14.0% high-risk, p<0.001), with 2.4% nodal recurrences (1.2% low/intermediate-risk vs. 4.1% high-risk). Conclusion High-risk patients had significant upstaging, LN metastasis, and recurrence rates. Even in low/intermediate-risk groups, some patients exhibited LN metastasis and nodal recurrence, underscoring the importance of comprehensive surgical staging, including PALN evaluation, for precise diagnosis and treatment.

Objective: This study aimed to explore differences in disease extent based on the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) classification and to establish personalized staging surgery strategies in patients with preoperatively presumed uterusconfined endometrial cancer. Methods: In this retrospective, single-center study, we reviewed the medical records of patients with endometrial cancer. These patients were classified according to the ProMisE classification based on tissue samples obtained from dilation and curettage or staging surgeries, and the disease extent was analyzed based on pathologic reports. Results: A total of 345 patients were clinically estimated to be in stage 1/2 before staging surgery, with immunohistochemistry (IHC) results available. This cohort included 332 patients (96.2%) with clinical stage 1 and 13 patients (3.8%) with stage 2 based on the 2009 FIGO staging system. Among these, 81 patients (23.5%) were assigned to an mismatch repair deficient group (MMRd), 33 (9.6%) to an abnormal p53 group, and 123 (71.1%) to a no specific molecular profile (NSMP) group. Overall, 13 patients had nodal metastasis, with a higher rate observed in the abnormal p53 group (1.2%, 12.1%, and 2.2% for the MMRd, abnormal p53, and NSMP groups, respectively, p=0.013). One patient (0.3%) had parametrial metastasis and four (1.1%) had peritoneal metastasis. Conclusion Patients with abnormal p53 IHC results exhibited a higher likelihood of lymph node metastasis, even when initially presumed to be at an early stage. For the abnormal p53 group, proactive lymphadenectomy surgery appears beneficial for accurate staging and establishing a subsequent treatment plan.

Objective: Serous tubal intraepithelial carcinoma (STIC), a potential precursor of high-grade serous carcinoma, is associated with subsequent carcinomas development. This study aimed to identify cases of STIC and serous tubal intraepithelial lesions (STIL) and examine clinical outcomes and patterns of care in BRCA1/2 mutations carriers undergoing risk-reducing salpingo-oophorectomy (RRSO), as well as patients with incidental STIC/STIL after benign gynecologic surgery. Methods: This retrospective study was conducted at six institutions to examine patients with isolated STIC/STIL. Demographic, adjuvant treatment, and follow-up data were collected from the date of implementation of Sectioning and Extensively Examining the Fimbriated end protocol, which varied from 2006 to 2015, until December 2022. Results: We analyzed the data of 1,119 women who underwent RRSO and were carriers of BRCA1/2 mutations. The detection rate of isolated STIC/STIL was 1.70%. No patient with STIC/STIL received adjuvant chemotherapy or staging operations. The institutions used different surveillance intervals and methods, with the most common being a 3–6 month interval (11 of 19 patients) and gynecological sonography (17 of 19 patients). All patients remained with no evidence of disease (NED) throughout the follow-up period (2–121 months). Additionally, we analyzed data from five women with incidental STIC/ STIL diagnosed after benign gynecological surgery; one woman underwent staging surgery.During the follow-up period (3–46 months), all patients remained in NED. Conclusion While patient monitoring after STIC/STIL detection may be considered due to the minimal risk of carcinoma, excessive concern may not be necessary. Furthermore, adjuvant chemotherapy should be considered only with caution.

Objective: To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. Methods: Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status.Kaplan–Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. Results: A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS).BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. Conclusion Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Objective: To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. Methods: Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status.Kaplan–Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. Results: A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS).BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. Conclusion Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Objective: To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. Methods: Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status.Kaplan–Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. Results: A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS).BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. Conclusion Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.