Toyomi Satoh

Annual Report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2022 and Annual Treatment Report for 2017

ABSTRACT Aim To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2022 and the Annual Treatment Report for 2017, on the outcomes of patients who started treatment in 2017. Methods 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 2022 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2017 was analyzed by using the Kaplan–Meier, log–rank, and Wilcoxson tests. Results Treatment was initiated in 2022 for 8039 patients with cervical cancer, 14 518 with endometrial cancer, 8524 with ovarian, tubal, and peritoneal cancer, 2360 with ovarian borderline tumors, and with the others (270 vulvar cancer, 179 vaginal cancer, 539 uterine sarcoma, 48 uterine adenosarcoma, 158 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients who initiated treatment in 2017 were as follows. For cervical cancer, the rates were 93.0%, 76.1%, 59.5%, and 28.3% for Stages I, II, III, and IV, respectively. For endometrial cancer, the rates were 94.9%, 88.8%, 72.7%, and 28.9% for Stages I, II, III, and IV, respectively. For ovarian cancer, the rates were 91.7%, 76.6%, 54.4%, and 45.2% for Stages I, II, III, and IV, respectively. Conclusion The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Comparison of MR Imaging of High-grade Serous Carcinomas with and without Homologous Recombination-deficiency

MRI findings of high-grade serous carcinoma (HGSC) with and without homologous recombination deficiency (HRD) were compared to explore the feasibility of using MRI as a genetic predictor. We retrospectively reviewed MRI data from HRD-positive and HRD-negative HGSC and evaluated tumor size, appearance, apparent diffusion coefficient (ADC), time-intensity curve, and several dynamic contrast-enhanced curve descriptors. Age, primary site, tumor stage, bilaterality, presence of lymph node metastasis, presence of peritoneal metastasis, and tumor marker levels were also compared. Forty-eight patients with HRD-positive HGSC (17 patients with BRCA1 variant, 9 patients with BRCA2 variant, and 22 without BRCA variants) and 18 patients with HRD-negative HGSC were included. The HRD-negative patients' mean age was 67 years, which was significantly higher than that of the HRDpositive patients (60 years, P = 0.011). High-risk time-intensity curve (TIC) patterns were more common in HRD-negative tumors (94%) than in HRD-positive tumors (63%; P = 0.047). Tumors without HRD exhibited significantly higher wash-in rates (P = 0.023). Additionally, unresectable lymph node metastases were significantly more frequent in HRD-negative patients (P = 0.013). No significant differences were observed in the other evaluated factors. The comparison between HGSC with and without HRD revealed that HGSC without HRD was significantly associated with older age, a higher likelihood of exhibiting a high-risk TIC pattern, a higher wash-in rate, and a higher frequency of unresectable lymph node metastasis.

Questionnaire-based survey on the extent of lymph node dissection during interval debulking surgery after neoadjuvant chemotherapy for patients with advanced ovarian cancer in the Gynecologic Cancer Study Group of JCOG

The significance of lymph node dissection (LND) in primary debulking surgery (PDS) for advanced ovarian cancer was demonstrated in the LION trial. However, the role and the current practices of LND during interval debulking surgery (IDS) remains unclear. We aimed to conduct a survey of the current LND practices. A questionnaire-based survey regarding the criteria and extent of LND for advanced ovarian cancer was conducted by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (JCOG). We defined enlarged lymph nodes as 10 mm or more in the short axis on imaging. This study included data from 51 institutions. Factors contributing to the decision regarding the extent of LND included performance status, completeness of cytoreductive surgery excluding the lymph nodes, and age. Regarding PDS cases with enlarged lymph nodes, 90% of all institutions opted for systematic LND (SyLND) or removal of only the enlarged lymph nodes (SeLND). In IDS cases with enlarged lymph nodes after neoadjuvant chemotherapy (NACT), 15 (29%) and 35 (69%) institutions opted for SyLND and SeLND, respectively. In contrast, in IDS cases in which enlarged lymph nodes were reduced after NACT, approximately half the institutions opted for no LND. This study found no established standard treatment for LND during IDS in patients with enlarged lymph nodes among the JCOG institutions. Thus, further prospective studies comparing the prognostic outcomes with or without LND are warranted.

Comparison of Benign, Borderline, and Malignant Ovarian Seromucinous Neoplasms on MR Imaging

This study aimed to compare MRI findings among benign, borderline, and malignant ovarian seromucinous neoplasms. We retrospectively analyzed MRI data from 24 patients with ovarian seromucinous neoplasms-seven benign, thirteen borderline, and six malignant. The parameters evaluated included age, tumour size, morphology, number, height, apparent diffusion coefficient (ADC) values, T2 ratios, time-intensity curve (TIC) descriptors, and TIC patterns of the mural nodules. Additionally, we examined the T2 and T1 ratios of the cyst contents, tumour markers, and the presence of endometriosis. We used statistical tests, including the Kruskal-Wallis and Fisher-Freeman-Halton exact tests, to compare these parameters among the three aforementioned groups. The cases showed papillary architecture with internal branching in 57% of benign, 92% of borderline, and 17% of malignant cases. Three or fewer mural nodules were seen in 57% of benign, 8% of borderline, and 17% of malignant cases. Compared to benign and borderline tumours, mural nodules of malignant neoplasms had significantly increased height (P = 0.015 and 0.011, respectively), lower means ADC values (P = 0.003 and 0.035, respectively). The mural nodules in malignant cases also demonstrated significantly lower T2 ratios than those in the benign cases (P = 0.045). Most neoplasms displayed an intermediate-risk TIC pattern, including 80% benign, 83% borderline, and 60% malignant neoplasms, and no significant differences were observed. Most benign and borderline tumours exhibited a papillary architecture with an internal branching pattern, whereas this feature was less common in malignant neoplasms. Additionally, benign tumours had fewer mural nodules compared to borderline tumours. Malignant neoplasms were characterized by mural nodules with increased height and lower ADC values than those in benign and borderline tumours. Interestingly, all three groups predominantly exhibited an intermediate-risk TIC pattern, emphasizing the complexity of diagnosing seromucinous neoplasms using MRI.

Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial

In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. This

Quality of care measurement for patients with ovarian cancer in Japan

Abstract Aim Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high‐quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. Methods A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital‐based cancer registry of patients diagnosed in 2018. All patients receiving first‐line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. Results The adherence rate ranged from 22.6% for “Estrogen replacement within 6 months of operation” to 93.5% for “Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II.” Of 580 hospitals, 184 submitted the reasons for nonadherence. Conclusions The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

The Utility of Apparent Water Diffusion Coefficient Maps for Evaluating the Presence of Myometrial Invasion in Patients with Endometrial Cancer

To assess the utility of apparent diffusion coefficient maps (ADC) for diagnosing myometrial invasion (MI) in endometrial cancer (EC). This retrospective study included 164 patients (mean age, 56 years; range, 25-89 years) who underwent preoperative MRI for EC with <1/2 MI or no MI between April 2016 and July 2023. Five sequences were evaluated: T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), ADC, dynamic contrast-enhanced T1-weighted imaging (DCE-T1WI), and contrast-enhanced T1WI (CE-T1WI). Three experienced radiologists independently assessed the sequences for MI. For ADC, MI was determined if the endometrial-myometrial junction-tumor boundary had disappeared. Additionally, the assessment of MI was performed using the combination of T2WI, DWI, and ADC, as well as T2WI, DCE-T1WI, and CE-T1WI. The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) for the presence of MI were calculated and compared between the sequences and combinations. Inter-reader agreement was assessed using kappa (κ) statistics. The sensitivity of ADC was significantly higher than T2WI (P < 0.001) and DCE-T1WI (P = 0.018) for one reader and significantly higher than CE-T1WI (P = 0.045 and 0.043) for two readers. The specificity of ADC was significantly lower than T2WI (P = 0.015 and < 0.001) and CE-T1WI (P = 0.031 and 0.01) for two readers and significantly lower than DCE-T1WI (P = 0.031) for one reader. The AUC of ADC was significantly higher than T2WI (P = 0.048) and DCE-T1WI (P = 0.049) for one reader. The combination including ADC showed higher positive predictive value for all three readers compared to any sequence or combination including contrast enhancement. Additionally, ADC demonstrated the highest agreement rates. ADC had high sensitivity for MI and the highest agreement rate among all sequences. Thus, this sequence, combined with other sequences, can be crucial for a comprehensive evaluation of MI.

Salvage hysterectomy for persistent residual cervical cancer: assessment of prognostic factors

In this multicenter retrospective cohort study of 99 patients who underwent salvage hysterectomy for residual disease in the uterine cervix following the completion of definitive radiotherapy for cervical cancer across 25 Japan Clinical Oncology Group-affiliated centers from 2005-2014, (i) time duration from the completion of definitive radiotherapy to the diagnosis of residual disease in the uterine cervix, (ii) salvage hysterectomy surgical margin status, and (iii) extent of residual disease, were independently associated with progression-free survival (PFS). Specifically, (i) time duration to identify residual disease of >62 days was associated with decreased PFS compared to ≤62 days (4-year rates 21.8% vs. 55.0%, adjusted-hazard ratio [aHR]=2.69, 95% confidence interval [CI]=1.55-4.67); (ii) presence of tumor in the surgical margin of hysterectomy specimen was associated with 4 times increased risk of disease progression compared to tumor-free surgical margin (4-year PFS rates 0% vs. 45.3%, aHR=4.27, 95% CI=2.20-8.29); and (iii) hazards of disease progression was 4.5-fold increased when the residual disease extended beyond the uterine cervix compared to residual disease within the uterine cervix only (4-year PFS rates 11.1% vs. 50.6%, aHR=4.54, 95% CI=2.60-7.95). In the absence of these 3 prognostic factors, 4-year PFS rate reached nearly 80% (78.6%, SAL-HYS criteria). In sum, these data suggested that early detection of persistent, residual disease following definitive radiotherapy for cervical cancer may be the key to improve survival if salvage hysterectomy is considered as a tailored treatment option. Ideal surgical candidate would be uterine cervix-contained disease and assurance of adequate tumor-free surgical margin.

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis

To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC). We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events. For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70-0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85-1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68-0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49-1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99-1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63-0.86). Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.

Survival and reproductive outcomes after fertility‐sparing surgery performed for borderline epithelial ovarian tumor in Japanese adolescents and young adults: Results of a retrospective nationwide study

AbstractObjectiveEpithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression‐free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility‐sparing surgery (FSS). We conducted a Japan‐wide study to understand post‐FSS prognosis in relation to clinical characteristics and types of FSS performed.MethodsWe analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15–39 years) who underwent FSS for BOT between 2009 and 2013.ResultsMedian (range) age was 30 (15–39) years, and median observation time was 70 (2–120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five‐year overall survival was 99.5% among patients with stage I and 100% among those with stage II–IV. Five‐year progression‐free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post‐FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16–3.00; p = 0.0090).ConclusionPost‐FFS outcomes in terms of overall and progression‐free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II–IV and for those with stage I but a positive peritoneal cytology. A long‐term prospective observation is needed before reproductive outcomes can be fully established.

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.

The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer

The fifth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was published in 2020. The guidelines contain 6 chapters-namely, (1) overview of the guidelines; (2) epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (4) borderline epithelial tumors of the ovary; (5) malignant germ cell tumors of the ovary; and (6) malignant sex cord-stromal tumors. Furthermore, the guidelines comprise 5 algorithms-namely, (1) initial treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (2) treatment for recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) initial treatment for borderline epithelial ovarian tumor; (4) treatment for malignant germ cell tumor; and (5) treatment for sex cord-stromal tumor. Major changes in the new edition include the following: (1) revision of the title to "guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer"; (2) involvement of patients and general (male/female) participants in addition to physicians, pharmacists, and nurses; (3) clinical questions (CQs) in the PICO format; (4) change in the expression of grades of recommendation and level of evidence in accordance with the GRADE system; (5) introduction of the idea of a body of evidence; (6) categorization of references according to research design; (7) performance of systematic reviews and meta-analysis for three CQs; and (8) voting for each CQ/recommendation and description of the consensus.

Diagnostic accuracy and prognostic factors of uterine serous carcinoma in Japanese women: a multi-center study

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. 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. 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. 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.

Exploratory Study on the Correlation Between HRD Score and PARPi Efficacy Based on Chinese Ovarian Cancer Patients

This study plans to retrospectively include 470 initial surgical specimens from 470 patients with epithelial ovarian, fallopian tube or primary peritoneal cancers who were treated with PARPi maintenance therapy in the hospital from 2018.01 to 2024.01. All patients included would be scored by the proprietary HRD ADx-GSS® algorithm with the detecting results of the three genomic statuses including heterozygous omission (LOH), telomere allelic imbalance (TAI), and large-segment translocation (LST). Finally, the correlation between the HRD scores and the prognosis of Chinese ovarian cancer patients and the efficacy of using PARPi as maintenance treatment would be explored.

Platine, Avastin and OLAparib in 1st Line

Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB - IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance.