No abstract available.

OBJECTIVE: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. METHODS: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. RESULTS: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. CONCLUSION: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model.
Cohort Studies ; Cytoreduction Surgical Procedures ; Disease-Free Survival ; Drug Therapy ; Humans ; Methods ; Multivariate Analysis ; Ovarian Neoplasms ; Recurrence ; Retrospective Studies

Objective: To assess the incidence of bevacizumab-associated gastrointestinal (GI) perforation during first-line treatment of patients with ovarian, fallopian tube, or peritoneal cancer receiving neoadjuvant chemotherapy (NAC) in Japanese real-world clinical practice. Methods: A retrospective study was conducted using a healthcare claims database owned by Medical Data Vision Co., Ltd. (study period, 2008–2020). Patients who initiated first-line treatment of ovarian, fallopian tube, or peritoneal cancer were identified and divided into NAC and primary debulking surgery (PDS) groups. The incidence of bevacizumab-associated GI perforation was compared within the NAC group and between the groups. Results: Paclitaxel + carboplatin (TC) was most commonly used as first-line treatment (39.5% and 59.6% in the NAC and PDS groups, respectively). TC + bevacizumab was used in 9.3% and 11.6% of patients in the NAC and PDS groups, respectively. In the NAC group receiving TC, the proportion of patients with risk factors for GI perforation was lower among patients with versus without concomitant bevacizumab. The incidence of GI perforation in the NAC group was 0.38% (1/266 patients) in patients receiving TC + bevacizumab and 0.18% (2/1,131 patients) in patients receiving TC without bevacizumab (risk ratio=2.13; 95% confidence interval [CI]=0.19 to 23.36; risk difference=0.20; 95% CI=−0.58 to 0.97). None of the 319 patients in the PDS group receiving TC + bevacizumab had GI perforation. Conclusion No notable increase was observed in GI perforation associated with NAC containing bevacizumab. We conclude that bevacizumab is prescribed with sufficient care in Japan to avoid GI perforation.

Objective: We have established 4 histopathologic subtyping of high-grade serous ovarian cancer (HGSOC) and reported that the mesenchymal transition (MT) type has a worse prognosis than the other subtypes. In this study, we modified the histopathologic subtyping algorithm to achieve high interobserver agreement in whole slide imaging (WSI) and to characterize the tumor biology of MT type for treatment individualization. Methods: Four observers performed histopathological subtyping using WSI of HGSOC in The Cancer Genome Atlas data. As a validation set, cases from Kindai and Kyoto Universities were independently evaluated by the 4 observers to determine concordance rates. In addition, genes highly expressed in MT type were examined by gene ontology term analysis. Immunohistochemistry was also performed to validate the pathway analysis. Results: After algorithm modification, the kappa coefficient, which indicates interobserver agreement, was greater than 0.5 (moderate agreement) for the 4 classifications and greater than 0.7 (substantial agreement) for the 2 classifications (MT vs. non-MT). Gene expression analysis showed that gene ontology terms related to angiogenesis and immune response were enriched in the genes highly expressed in the MT type. CD31 positive microvessel density was higher in the MT type compared to the non-MT type, and tumor groups with high infiltration of CD8/CD103 positive immune cells were observed in the MT type. Conclusion We developed an algorithm for reproducible histopathologic subtyping classification of HGSOC using WSI. The results of this study may be useful for treatment individualization of HGSOC, including angiogenesis inhibitors and immunotherapy.

OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.
Adult ; Aged ; Aged, 80 and over ; Female ; *Groin ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/pathology ; Magnetic Resonance Imaging ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node/*pathology ; Sentinel Lymph Node Biopsy/*methods ; Vulvar Neoplasms/*pathology/surgery

Objective: 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. Methods: 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. Results: 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). Conclusion 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.

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Objective: 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. Methods: 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. Results: 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. Conclusion 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.

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.

Objective: Owing to the potential benefits of minimally invasive hysterectomy for endometrial cancer, the practice pattern has recently shifted in Japan. This study examined the trends in minimally invasive surgery (MIS) in patients with endometrial cancer in Japan. Methods: This retrospective observational study examined the Japan Society of Obstetrics and Gynecology Tumor Registry database between 2015–2019. This study examined the time-specific proportion change and predictors of MIS use in initial endometrial cancer treatment in Japan, and compared it with the use of abdominal surgery. Additionally, the association between hospital surgical treatment volume and MIS use was examined. Results: A total of 14,059 patients (26.5%) underwent minimally invasive hysterectomy, and 39,070 patients (73.5%) underwent abdominal hysterectomy in the study period. Patients who underwent MIS were more likely to be treated at high-volume centers, younger, central, or western Japan residents, registered in recent years, and had a tumor with stage I disease, type 1 histology, and less myometrial invasion (all adjusted p<0.05). The proportion of MIS treatments increased from 19.1% in 2015 to 34.3% in 2019 (p<0.001). On multivariable analysis, treatment at high-volume centers was a contributing factor for MIS (adjusted odds ratio=3.85; 95% confidence interval=3.44–4.30). MIS at high-volume centers increased significantly from 24.8% to 41.0% (p<0.001) during the study period, whereas MIS at low-volume centers remained at median 8.8%. Conclusion MIS has increased significantly in recent years, accounting for nearly 34% of surgical management of endometrial cancer in Japan. High-volume treatment centers take the lead in performing MIS.