Objective: DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. Methods: Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigatorassessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. Results: In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32–1.12) and durvalumab + olaparib (0.44, 95% CI=0.22–0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. Conclusion Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/ paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.

The Japan Society of Gynecologic Oncology (JSGO) guideline for the treatment of uterine body neoplasm are revised from the 2018 guideline. This guideline aimed to provide standardized care for uterine body neoplasm, indicate appropriate current treatment methods for uterine body neoplasm, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden on patients by promoting the performance of appropriate treatment, and enhance mutual understanding between patients and healthcare professionals. The guidelines were prepared through the consensus of the JSGO guideline committee, based on a careful review of evidence from the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The main features of the 2023 revision are as follows: 1) The Guidelines Formulation Committee members were asked to understand Minds' medical guideline development method in advance. 2) The clinical question (CQ) was changed to Patient, Intervention, Comparison, Outcome format as much as possible. 3) Introduced the "body of evidence," which summarizes the results of research reports collected for the CQs by outcome and study design, and the strength of evidence for each body of evidence was rated from levels A to D. 4) Introduction of systematic reviews in some CQs. 5) The strength of evidence, the balance of benefits and harms, value and hope for patients, and clinical applicability were considered while drafting recommendations. Herein, we present the English version of the JSGO guidelines 2023 for the treatment of uterine body neoplasm.

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/m 2or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , 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.

Laterally extended endopelvic resection (LEER) is a surgical option for patients with laterally recurrent gynecological malignancies to preserve sciatic nerve function [1]. However, when a laterally recurrent tumor involves the sacrum, debulking surgery is generally abandoned because the surgical excision line is outside the standard LEER. Since its technical feasibility and oncological safety have been demonstrated, sacrectomy for recurrent rectal cancer is now considered the treatment of choice [2]. Theoretically, if complete resection is deemed possible, LEER and sacrectomy (beyond-LEER) may be the treatments of choice for recurrent gynecological malignancies. However, the technical feasibility of beyond-LEER has not been reported. In this video, we demonstrate the step-by-step procedure of laparoscopy-assisted beyond-LEER in a patient with platinum-sensitive recurrent ovarian cancer. The patient, with stage IVA ovarian cancer, was in complete remission after debulking surgery and chemotherapy.At the 13-month-platinum-free interval, a solitary recurrent tumor, involving the right internal iliac vessels and infiltrating the right sacral foramen (S3), was detected. Thus, second-line chemotherapy was initially introduced. During 6 months of chemotherapy, the tumor size remained unchanged and no other metastatic lesions were detected. Therefore, surgical resection was planned. Laparoscopy-assisted beyond-LEER was performed, and complete resection without tumor exposure was accomplished. No sign of recurrence 9 months post debulking surgery has been noted. This is the first report to demonstrate the technical feasibility of laparoscopy-assisted beyond-LEER. Table 1 presents a comparison with cases wherein open total pelvic exenteration with low-sacrectomy (TPES) was performed for recurrent rectal cancer. Forty-nine cases of open TPES demonstrated operation time, 11.5 hours; blood loss volume, 2,630 mL; and length of stay, 24.5 days [3]. These results are similar to the findings in our case: operation time, 11 hours; blood loss volume, 1,700 mL; and length of stay, 35 days. We suggest that the benefit of laparoscopy cannot be demonstrated because TPES is a different procedure compared with the beyond LEER.Kimura et al. [4] demonstrated that laparoscopic TPES for recurrent rectal cancer might have a benefit of reduced blood loss. The advantages of laparoscopy during our multidirectional procedure include not only the possibility of reducing blood loss but also the quick closureof abdominal wound and ease of keeping wound clean while changing patient’s position during sacrectomy. However, due to the limited case and follow up periods, further studies are required to determine the efficacy of this novel surgery and real advantage of laparoscopy.The informed consent for use of this video was taken from the patient.

Objective: In advanced ovarian cancer, achieving R0 resection is a critical strategy for improving prognosis. However, even with R0 resection, the prognosis of patients with a high tumor burden remains poor. This study aimed to assess whether the introduction of poly(ADP-ribose) polymerase inhibitors (PARPi) has enhanced outcomes in such cases. Methods: We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (FIGO) stage III–IV ovarian cancer treated between January 2015 and December 2021. Patients were classified into Group A (pre-PARPi introduction) and Group B (post-PARPi introduction). Complete macroscopic resection was defined as R0. Progressionfree survival (PFS), stratified by the Aletti Surgical Complexity Score (Aletti_SCS), was the primary endpoint and was evaluated using Cox regression models. Results: A total of 434 patients were included. In Group A, among those who achieved R0, the median PFS was 23.5 months for patients with high Aletti_SCS (95% confidence interval [CI]=14–30) and not reached for those with low Aletti_SCS (95% CI=30–not reached; adjusted hazard ratio [HR]=0.36, 95% CI=0.20–0.62). In Group B, the median PFS was not reached in both patients with high Aletti_SCS (95% CI=not reached–not reached) and low Aletti_SCS (95% CI=22–not reached; adjusted HR=4.98, 95% CI=1.14–21.78). Conclusion Following the introduction of PARPi, there was a trend toward improved PFS in patients with a higher Aletti_SCS who underwent R0 resection. These findings suggest that R0 resection may improve prognosis even in cases with a high tumor burden in the PARPi era.

Objective: The combination of cancer and hypercoagulable states is often called Trousseau syndrome. In particular, cerebral infarction caused by Trousseau syndrome is reported to have a poor prognosis. In gynecology, there are many reports of ovarian cancer and a few of uterine cancer. Since there has been no comprehensive report of Trousseau syndrome in cervical cancer, we aimed to summarize Trousseau syndrome in cervical cancer. Methods: Cerebral infarction caused by cancer-related arterial thrombosis was defined as Trousseau syndrome. Patients with cervical cancer diagnosed at our hospital between January 2014 and December 2021 were retrospectively reviewed using the hospital’s medical records. Results: A total of 1,432 patients were included in the study. Trousseau syndrome occurred in 6 patients (0.4%). The mean age of patients with Trousseau syndrome was 63 years (range:53–78 years). Of the 6 patients who developed Trousseau’s syndrome, 4 patients had it before or during initial treatment, and 2 during recurrent/relapsed disease treatment. The 4 patients who developed the syndrome before or during initial treatment had advanced disease: 1 in stage IIIC and 3 in stage IVB. In all cases, the disease was associated with progressive distant metastasis. The median survival time from the onset of Trousseau syndrome was 1 month (range: 0–6 months). Conclusion Cervical cancer causes Trousseau syndrome in cases of advanced disease with a short time between the onset of the syndrome and mortality.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: The combination of cancer and hypercoagulable states is often called Trousseau syndrome. In particular, cerebral infarction caused by Trousseau syndrome is reported to have a poor prognosis. In gynecology, there are many reports of ovarian cancer and a few of uterine cancer. Since there has been no comprehensive report of Trousseau syndrome in cervical cancer, we aimed to summarize Trousseau syndrome in cervical cancer. Methods: Cerebral infarction caused by cancer-related arterial thrombosis was defined as Trousseau syndrome. Patients with cervical cancer diagnosed at our hospital between January 2014 and December 2021 were retrospectively reviewed using the hospital’s medical records. Results: A total of 1,432 patients were included in the study. Trousseau syndrome occurred in 6 patients (0.4%). The mean age of patients with Trousseau syndrome was 63 years (range:53–78 years). Of the 6 patients who developed Trousseau’s syndrome, 4 patients had it before or during initial treatment, and 2 during recurrent/relapsed disease treatment. The 4 patients who developed the syndrome before or during initial treatment had advanced disease: 1 in stage IIIC and 3 in stage IVB. In all cases, the disease was associated with progressive distant metastasis. The median survival time from the onset of Trousseau syndrome was 1 month (range: 0–6 months). Conclusion Cervical cancer causes Trousseau syndrome in cases of advanced disease with a short time between the onset of the syndrome and mortality.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.