Nobuo Yaegashi

Trends and characteristics of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer in Japan: a survey by the Gynecologic Oncology Committee of the Japan Society of Obstetrics and Gynecology

The objective of this study was to examine the current trends in fertility-sparing (FS) treatment for young atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients in Japan. This study was conducted by the Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology (JSOG) in the 2017-2018 fiscal year. A nationwide, retrospective questionnaire-style survey-as performed. We collected the data of 413 patients from 102 JSOG gynecological cancer registered institutions. FS treatment was performed with medroxyprogesterone (MPA) (87.2%) or MPA + metformin (11.6%). Pathological complete remission (CR) after initial treatment was achieved in 78.2% of patients. The significant clinicopathological factors correlated to CR after initial treatment were histology (AEH vs. endometrioid carcinoma grade 1 [ECG1]), body mass index (BMI) (<25 vs. ≥25 kg/m²), and treatment period (<6 vs. ≥6 months). ECG1, time to complete remission (TTCR) ≥6 months, maintenance therapy (-), and pregnancy (-) were associated with a significantly higher risk of recurrence on multivariate analysis. The total pregnancy rate was 47%, and the live birth rate was 40.1%. Patients who received infertility treatments showed a higher live birth rate (50.6%) than those who did not (7.7%). In this survey, we confirmed that FS treatment in Japan is centered on MPA alone and in combination with metformin, and that the treatment efficacy is similar to that reported in previous reports. A multicenter survey study in Japan showed FS treatment for young AEH and EC patients in compliance with the indications is feasible.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013

AbstractTo provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.

Current status of hereditary breast and ovarian cancer practice among gynecologic oncologists in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO)

The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management. A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC. A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities. Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management.

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study

Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined. The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks. Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20-49, 20-50, and 17-26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78-0.88; aHR=0.78, 95% CI=0.75-0.83; and aHR=0.90, 95% CI=0.86-0.95 for endometrial, cervical, and ovarian tumors). Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

Rethinking the significance of surgery for uterine cervical cancer

AbstractBackgroundTreatment strategies based on histological subtypes are unestablished.AimsRethinking the significance of surgery for uterine cervical cancer.MethodsUsing the database of cervical cancer stages IB–IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging. In stage IB (FIGO 2018) cervical cancer patients, there was no significant difference in treatment outcome according to histological type, but in stages IIA, IIB, and IIIC1 (FIGO 2018), the treatment outcome of nonsquamous cell carcinoma was significantly worse than that of squamous cell carcinoma. Considering post‐treatment health care, it is important to consider ovarian preservation in young patients with cervical cancer, up to stage IIA (FIGO 2018) for squamous cell carcinoma and stage IB1 (FIGO 2018) for nonsquamous cell carcinoma, after careful evaluation of clinicopathological factors before surgery.DiscussionLocally advanced adenocarcinoma of the cervix is a rare and refractory cancer that has been shown to have low radiosensitivity, and its treatment outcome is still unsatisfactory. A new therapeutic strategy involving multidisciplinary treatment in combination with perioperative chemotherapy at a facility that can provide highly curative surgical treatment is desired.ConclusionMinimally invasive surgery is being introduced for the treatment of early‐stage cervical cancer. However, the number of eligible cases should be expanded in a phased manner, based on an objective evaluation of surgical outcomes at the facilities. Omics analysis may be useful to develop a new treatment for human papillomavirus nonrelated cervical cancer, represented by gastric mucinous carcinoma.

The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee

The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery. This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model. For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.

Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study

Gastric-type mucinous carcinoma (GAS) is a novel variant of uterine cervix mucinous carcinoma. GAS is a distinct entity that can be distinguished from typical endocervical adenocarcinoma (UEA). In Japan, postoperative adjuvant therapy for cervical cancer includes not only radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) but also chemotherapy in many cases. However, no previous studies have analyzed adjuvant therapy for GAS. In the present study, we investigated the efficacy of adjuvant therapy for GAS. This was a preplanned secondary analysis of a dataset from previous nationwide, retrospective, observational study. The study population comprised women with stage I-II GAS who underwent surgery. Progression-free survival (PFS) and overall survival (OS) were compared among patients who did and did not receive adjuvant therapy using the Kaplan-Meier method. Data were analyzed for a total of 102 enrolled patients, who were classified as low- (17 patients), intermediate- (37 patients), or high risk (48 patients) based on the risk of postoperative cervical cancer recurrence. In the intermediate-risk group, median survival could not be assessed due to a lack of sufficient events, but the no-adjuvant and RT groups tended to exhibit better prognoses. In contrast, within the high-risk group, patients in the RT subgroup exhibited a trend towards better PFS and OS than those in the CCRT and chemotherapy groups. The prognosis of GAS was confirmed to be poor, even in cases of early-stage cancer and following surgical resection. Chemotherapy strategies, including CCRT as postoperative adjuvant therapy, tend to have a poor prognosis.

Cost-effectiveness analysis of hospital treatment volume and survival outcomes in endometrial cancer in Japan

Hospital treatment volume affects survival in patients with endometrial cancer; notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan. A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and high-volume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses. A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000 with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or low-volume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and low-risk groups, respectively. Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer.