Journal of Gynecologic Oncology最新文献

Objective: This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women.

Methods: The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry.

Results: USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III-IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma.

Conclusion: USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.

Objective: This systematic review and meta-analysis aimed to assess the impact of postoperative adjuvant chemotherapy on recurrence and mortality in stage IC granulosa cell tumors (GCTs).

Methods: We searched the PubMed, Embase, and Cochrane Library for studies published up to December 1, 2024, comparing the oncological outcomes of adjuvant chemotherapy with observation in stage IC GCTs.

Results: Seventy studies were identified, with 12 included in the meta-analysis. Among 695 patients, 255 (36.7%) received postoperative adjuvant chemotherapy and 440 (63.3%) received observation. The overall recurrence and mortality rates were 18.7% and 7.6%, respectively. No significant differences were observed in survival outcomes between the adjuvant chemotherapy and observation groups, including recurrence rate (odds ratio [OR]=1.32; 95% confidence interval [CI]=0.67-2.58; p=0.424; I²=33%), mortality rate (OR=0.83; 95% CI=0.44-1.57; p=0.560; I²=0%), 5-year disease free survival (OR=0.88; 95% CI=0.18-4.18; p=0.868; I²=54%) and 5-year overall survival (OR=1.28; 95% CI=0.60-2.74; p=0.519; I²=0%). Subgroup analysis revealed no significant difference in recurrence rate between adjuvant chemotherapy and observation for both adult and juvenile GCTs, or between patients who underwent fertility-sparing surgery and those who did not. Additionally, no difference was found in recurrence rate between 'bleomycin, etoposide, and cisplatin' or 'etoposide and cisplatin' and 'paclitaxel combined with carboplatin or cisplatin' regimens.

Conclusion: Postoperative adjuvant chemotherapy did not provide additional benefits in disease recurrence or survival outcomes compared to observation in stage IC GCTs.

Trial registration: PROSPERO Identifier: CRD42024559478.

Objective: Gynecologic oncology is undergoing rapid development with continuous advances in treatment strategies, surgical techniques, and clinical research. Training programs must keep pace by providing future specialists with the necessary surgical skills and a solid understanding of evolving practices. This study aimed to examine the current state of gynecologic oncology training in Asia and to identify key challenges and opportunities for improvement.

Methods: A descriptive survey was conducted in October 2023 under the leadership of the Education Committee of the Asian Society of Gynecologic Oncology (ASGO). Key stakeholders involved in clinical training and policy-making from eight countries and regions (China, Hong Kong SAR, India, Japan, the Philippines, South Korea, Taiwan, and Thailand) responded to an online questionnaire assessing the structure and quality of their national training programs.

Results: Six of the eight countries/regions have official gynecologic oncology societies. Training duration was three years or more in five regions and two years in the remaining three. Seven reported conducting formal assessments of surgical skills. While five programs offered adequate exposure to minimally invasive surgery, three noted limitations. Satisfaction with research opportunities and overall training quality also varied. The most frequently cited concern was the lack of standardized curricula.

Conclusion: This regional overview reveals notable differences in training approaches across Asia. Standardizing educational frameworks and expanding collaborative initiatives - such as virtual tumor boards, elective rotations, and skills-based workshops - may help address current gaps and strengthen gynecologic oncology training in the region.

Objective: To explore the characteristics of pregnancy outcomes in patients with early-stage endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH) after successful fertility-sparing treatment.

Methods: This was a retrospective, single-center analysis of 481 patients with EEC/EAH who desired to conceive after successful fertility-sparing treatment from January 2015 to June 2023. Pregnancy outcomes across reproductive methods were compared.

Results: The pregnancy rate was 58.24% and the live birth rate was 48.65% in patients with EAH/EEC after successful fertility-preserving treatment. An age ≥35 years, BMI ≥25 kg/m², and hypertension were independent risk factors for failure of pregnancy. Higher pregnancy (65.77% and 63.64%) and live birth (53.08% and 48.86%) rates were achieved in the in vitro fertilization and embryo transfer (IVF-ET) and ovulation induction group than in the natural conception group (47.68% and 35.10%, respectively). The incidence of threatened abortion (56.52%), cervical insufficiency (5.58%), and placenta accrete/increta (11.15%) appeared to be numerically higher in patients with EAH/EEC than in epidemiological data. More than 5 times of hysteroscopic evaluation was an independent risk factor for placenta accreta/increta.

Conclusion: Assisted reproductive technology including IVF-ET and ovulation induction might be preferred for patients with EEC/EAH after successful fertility-sparing treatment to achieve a relatively better pregnancy outcome, though IVF-ET has a higher incidence risk of threatened abortion, preterm birth and placenta accreta/increta. Obstetricians should be prepared for the treatment of threatened abortion, cervical insufficiency, and placenta accreta/increta in patients with EEC/EAH once they become pregnant, especially in those receiving more than 5 times of hysteroscopic evaluation.

Objective: This study analyzed the efficacy of add-on atezolizumab to standard first-line bevacizumab-containing therapy in 56 Japanese patients with metastatic and recurrent cervical cancer treated across 8 sites under the Japanese Gynecologic Oncology Group between October 2018 and August 2021 in the BEATcc trial.

Methods: Patients were randomized to standard arm (standard therapy: cisplatin 50 mg/m² or carboplatin area under the curve of 5, paclitaxel 175 mg/m², and bevacizumab 15 mg/kg) or experimental arm (standard therapy with atezolizumab 1,200 mg).

Results: Of 56 patients, 30 were in experimental arm vs. 26, standard arm (age: 53.2±12.9 vs. 54.7±12.2 years). Median progression-free survival was 15.8 months (95% confidence interval [CI]=10.4-26.1) in experimental arm vs. 11.1 months (8.4-16.5) in standard arm (hazard ratio [HR]=0.51; 95% CI=0.26-1.01). Median overall survival was 34.1 months (23.2-38.6) in the experimental arm vs. 31.6 months (16.4-36.5), standard arm (HR=0.53; 95% CI=0.23-1.21). Objective response rate was 86.7% in experimental arm vs. 84.6%, standard arm. Complete response and partial response, respectively, were 23.3% and 63.3% in experimental arm and 26.9% and 57.7% in standard arm. Grade ≥3 adverse events occurred in 80.0%, experimental arm and 88.5%, standard arm. Gastrointestinal/genitourinary fistula incidence was lower in Japanese patients (1 patient receiving atezolizumab), likely due to stricter inclusion criteria.

Conclusion: Overall, add-on atezolizumab enhances the efficacy of bevacizumab and chemotherapy in Japanese patients as those in overall BEATcc population and could be considered a new first-line treatment option for metastatic, persistent, or recurrent cervical cancer in Japan.

Trial registration: ClinicalTrials.gov Identifier: NCT03556839.

Objective: Human papillomavirus (HPV) infection is a global public health concern and associated with cervical cancer. HPV genotype mapping has an essential role in prevention and control strategy in developing more suitable HPV vaccine for Indonesia.

Methods: This was a descriptive retrospective cross-sectional study from 2012 until 2022 at Kalgen Laboratory, Jakarta from all over the metropolitan regions. The total 76,413 samples were collected with consecutive sampling, which 694 excluded, thus final samples used were 75,719. HPV DNA test was performed using the polymerase chain reaction (PCR): SPF10-DEIA-LiPA25 methods. HPV genotyping procedures included DNA extraction, PCR using the HPV XpressMatrix kit, and hybridization.

Results: From 75,719 samples, 93.4% was negative for intraepithelial lesion or malignancy (NILM). Among 6.6% of total 75,719 samples of abnormal cytology groups, 53.8% were atypical squamous cells of undetermined significance (ASCUS), 32.9% were low grade intraepithelial lesion (LSIL), and 13.3% were high grade intraepithelial lesion (HSIL). The most common high risk HPV genotypes among HSIL were 16, 18, 52, 58, 33, 51, and 53. Single HPV infection was more common compared to multiple infections.

Conclusion: This study showed that HR-HPV types among HSIL were 16, 18, 52, 58, 33, 51, and 53. HPV 52 was the most frequent type among NILM, ASCUS, and LSIL. Thus, it could serve as a potential future reference to create a more suitable HPV nonavalent vaccine for Indonesian population based on its different epidemiology.

Objective: We aimed to identify the main oncogenic pathway by histological type of ovarian cancer based on Next-generation sequencing (NGS) test and to determine the correlation with clinical prognosis.

Methods: We conducted a retrospective review of 420 patients with ovarian cancer who underwent NGS testing at Asan Medical Center from June 1, 2017, to May 31, 2021. Identified mutations were categorized into seven oncogenic pathways that are most frequently associated with ovarian cancer.

Results: The average number of oncogenic pathways involved in each cancer patient was 1.76 (range, 0-6). TP53 mutation was the primary oncogenic pathway in patients with high-grade serous carcinoma (HGSC) (92.8%) and carcinosarcoma (87.5%). MAP kinase signaling was the primary oncogenic pathway in low-grade serous carcinoma (58.3%) and mucinous carcinoma (54.5%). The involvement of more diverse oncogenic pathways has been identified in patients with endometrioid carcinoma and clear cell carcinoma and PI3K-AKT-mTOR signaling and SWI/SNF family pathways were the most common in both groups. The involvement of the DNA damage response pathway showed an association with better progression free survival (PFS), but not with overall survival (OS) in patients with HGSC. On the other hand, the involvement of the RTK signaling family pathway showed an association with better OS despite no association with PFS in patients with HGSC.

Conclusion: The clinical prognosis may be improved by implementing targeted treatment tailored to the patient's genetic profile through NGS. Additional research is needed to determine whether the involvement of the RTK signaling family pathway is indeed associated with better OS and to identify the underlying reasons for this association.

Cervical cancer (CC) is a significant cause of cancer-related deaths in women and ranks as the fourth most common malignant tumor worldwide. Cervical histopathology is currently the primary diagnostic method for confirming the presence of CC. Tumor markers and imaging techniques play crucial roles in monitoring treatment effectiveness and prognostic follow-up. Unfortunately, these traditional examination methods are invasive and often lack sensitivity and accuracy. Therefore, there is a need for a less invasive and more sensitive test to facilitate early diagnosis, efficacy evaluation, and prognostic monitoring of CC. In recent years, liquid biopsy has been developed as a new detection method. It involves analyzing tumor components released into the peripheral circulation, such as cell-free RNA, circulating tumor DNA, circulating tumor cells, tumor-educated platelets, and exosomes. Liquid biopsy offers advantages such as being less invasive, highly reproducible, and capable of real-time monitoring. Moreover, liquid biopsy can play a crucial role in the early diagnosis of CC, guiding targeted therapy, assessing prognosis, and evaluating treatment effectiveness. This review focuses on the value of liquid biopsy application in CC, detection markers, and detection methods. It also explores how liquid biopsy can be used in the detection, prognosis, and monitoring the progression of CC. The advantages and limitations of liquid biopsy in CC are analyzed to promote its application and improve the diagnosis and treatment of the disease.

Objective: This study aims to elucidate the role of aryl hydrocarbon receptor nuclear transporter 2 (ARNT2) in cervical cancer (CC) and explore the potential mechanism by which ARNT2 promotes the progression of CC through the protein phosphatase 2A (PP2A)/Akt signaling pathway.

Methods: Bioinformatics tools were used to analyze the expression level of ARNT2 in cancer and its correlation with cancer prognosis. Western Blot and immunohistochemistry staining were used to detect the expression of ARNT2 protein in CC tissues and cells. ARNT2 was knocked down in SiHa and HeLa cells, respectively. Cell Counting Kit-8 assay and colony formation assay were used to detect changes in cell proliferation. Transwell assay and plate scratch assay were used to detect changes in cell migration and invasion. Western Blot assay was used to detect changes in the expression of PP2A/Akt signaling pathway after ARNT2 expression was downregulated. Finally, a CC xenograft tumor model was constructed to evaluate the effect of ARNT2 on SiHa cell tumorigenesis in vivo.

Results: ARNT2 is highly expressed in tumor tissues and cell lines. ARNT2 knockdown can significantly inhibit the proliferation, invasion and migration of SiHa and HeLa cells in vitro and in xenograft models. Further studies have shown that ARNT2 may promote tumor formation by regulating the PP2A/Akt pathway.

Conclusion: ARNT2 promotes the malignant biological behavior of CC cells through the PP2A/Akt signaling pathway, confirming its potential as a prognostic marker for CC.

Objective: Medroxyprogesterone acetate (MPA) is an effective fertility-preserving treatment for early endometrial cancer and atypical endometrial hyperplasia (AEH), and rarely leads to the development of extrauterine lesions (ELs). We aimed to clarify the characteristics of patients who developed ELs post-MPA therapy.

Methods: We analyzed the clinicopathological factors and prognoses of 319 patients with endometrioid carcinoma grade 1 (EMG1) and AEH treated with MPA at our institution. All patients underwent imaging before MPA treatment to rule out ELs.

Results: Seven patients (2.2%) with EMG1 showed EL after MPA treatment. Two patients developed EL during the initial treatment, 2 during repeated treatment, and 3 during follow-up. Two patients had peritoneal dissemination, 3 had regional lymph node metastasis, 1 had distant metastasis at the Virchow lymph node, and 1 had ovarian metastasis. ELs were diagnosed using imaging tests in 6 patients and elevated tumor markers in 3 (overlapping) patients. One patient was diagnosed with ELs pathologically after hysterectomy. Upon EL diagnosis, patients underwent standard treatment, including hysterectomy and chemotherapy, that was followed by a diagnosis of EMG1 for 5, EMG2 for 1, and EMG3 for 1 patient. One patient died 15 months after start of therapy and another died 119 months post-treatment initiation, while the others have been survived.

Conclusion: Only 2.2% of all patients developed ELs post-MPA treatment, but some cases were fatal. It is essential to conduct imaging tests and screen for tumor markers during and after MPA treatment regularly and also when cancer progression is suspected.