Woo Yeon Hwang

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Clinical practice guidelines for uterine corpus cancer: an update to the Korean Society of Gynecologic Oncology guidelines

The Korean Society of Gynecologic Oncology has updated its clinical practice guidelines for endometrial cancer to incorporate advancements in recent high-quality randomized controlled trials. These guidelines address evolving treatment paradigms, and are tailored to the Korean medical context. Key updates include a strong recommendation for doxorubicin/trabectedin combination therapy in metastatic or recurrent unresectable leiomyosarcoma based on the significant survival benefits demonstrated in a randomized controlled trial. For advanced or recurrent endometrial cancer, immune checkpoint inhibitors combined with chemotherapy have received strong recommendations, owing to their proven efficacy and increased accessibility in Korea. Conditional recommendations were made for combination therapies involving durvalumab and olaparib, reflecting their potential benefits, but acknowledging regulatory and accessibility constraints. These guidelines aim to provide evidence-based, practical strategies to optimize care for patients with endometrial cancer while addressing unmet clinical needs and adapting global advancements to Korea's healthcare environment.

Is restaging surgery quintessential in suspected early-stage epithelial ovarian cancer? An ancillary study of the Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3002)

To assess the necessity of restaging surgery for patients with suspected International Federation of Gynecology and Obstetrics (FIGO) stage I-II epithelial ovarian cancer (EOC) following incomplete surgical staging. This multicenter retrospective study evaluated patients with early-stage EOC referred for restaging. These patients were diagnosed with suspected FIGO stage I-II EOC between January 2007 and November 2022 after incomplete surgical staging, and no residual region was confirmed by radiological evaluation. Progression-free survival (PFS) and overall survival (OS) were examined. Among the 173 patients included in the study, 56 were assigned to the no restaging surgery group, and 117 to the restaging surgery group. After restaging, 23 were upstaged to other main stage. However, PFS and OS were not significantly different between the groups, also, dividing the groups into 4 groups who underwent chemotherapy and those who did not also did not show significant differences. In multivariate analysis, histologic grade independently influenced PFS outcomes. While restaging surgery resulted in upstaging in some patients, it was not associated with significant differences in PFS or OS in this retrospective analysis. However, the omission of any additional treatment warrants careful consideration and further discussion. Nevertheless, the observation that patients who did not undergo restaging surgery but received adjuvant chemotherapy did not show significantly different prognoses highlights the need for further research to establish appropriate treatment strategies tailored to diverse patient contexts.

Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study

This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes. In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107-0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group. In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm, lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC. Clinical Research Information Service Identifier: KCT0007309.

Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

The upper limit of optimal tumor size in patients with FIGO 2018 stage IB2 cervical cancer undergoing radical hysterectomy

Patients who undergo radical hysterectomy may require postoperative adjuvant radiotherapy, and all efforts should be made to reduce dual therapy in such patients. The aim of this study was to determine the optimal upper limit of tumor size in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB2 cervical cancer who undergo radical hysterectomy. We retrospectively reviewed the records of 114 patients with FIGO 2018 stage IB2 cervical cancer who underwent primary surgery either with (n=55) or without (n=59) adjuvant radiotherapy from June 2004 to December 2018. The inclusion criteria were as follows: women diagnosed with stage IB2 cervical cancer; primary radical surgery with pelvic lymph node dissection with or without para-aortic lymph node dissection; and patients treated with or without postoperative adjuvant radiation therapy, concurrent chemoradiation therapy, or chemotherapy. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal tumor size cut-off value. The optimal tumor size cut-off value was determined by the maximum sum of sensitivity and specificity. There were 55 and 59 patients treated with or without adjuvant therapy, respectively, after radical hysterectomy. Age, histologic type, and pelvic and para-aortic lymph node sampling/dissection status were similar between each group. The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 and 75, respectively. The decision for adjuvant treatment after radical hysterectomy in patients with stage IB2 cervical cancer was influenced by intermediate risk factors (lymphovascular space invasion, 23.7% vs 76.4%, p<0.001; deep 1/3 of invasion, 16.9% vs 61.8%, p<0.001) and high risk factors (lymph node metastasis, 0% vs 40.0%, p<0.001; involvement of parametrium, 1.7% vs 16.4%, p=0.007). According to the ROC curve results considering the best sensitivity and specificity, the optimal cut-off value of tumor size for predicting adjuvant treatment was 2.7 cm (sensitivity 0.85, specificity 0.52). The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 (34.2%) and 75 (65.8%), respectively. No significant differences were observed in the progression-free survival (p=0.22) and overall survival (p=0.28) rates between tumor size smaller than 2.7 cm and larger than 2.7 cm. A cervical tumor larger than 2.7 cm before radical surgery in stage IB2 may predispose to potential complications from combining radical hysterectomy and concurrent chemoradiation,. We consider that concurrent chemoradiation therapy is a more appropriate choice for tumor size over 2.7 cm per the revised FIGO 2018 criteria for stage IB2 cervical cancer.

Serum Human Epididymis Protein 4 as a Prognostic Marker in Cervical Cancer

Objectives The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer. Methods Sixty-seven patients with cervical cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups. Results The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age &lt;50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I–II: 33.3% vs III–IV: 66.7%; P = .017), large tumor size (&lt;4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma. Conclusions High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.