Nao Suzuki

Surveillance of laparoscopic systemic para‐aortic lymphadenectomy for patients with intermediate‐ and high‐risk endometrial cancer in Japan

Abstract Aim To evaluate the feasibility and safety of laparoscopic systemic para‐aortic lymphadenectomy (PALN) for endometrial cancer in a multicenter setting. Methods Clinical data from 403 patients who underwent laparoscopic PALN for intermediate‐ and high‐risk endometrial cancer under Japan's advanced medical care procedure between July 2017 and March 2020 were prospectively collected. Clinical background, surgical outcome, perioperative complications, and prognosis were analyzed. Results Histological subtype was 219 (54.4%) G1 or G2 endometrioid carcinoma, 64 (15.9%) G3 endometrioid carcinoma, 64 (15.9%) serous carcinoma, 24 (6.0%) carcinosarcoma, 15 (3.7%) clear cell carcinoma, and 17 (4.2%) others. Simple hysterectomy was performed in 180 cases (44.7%) and modified radical hysterectomy (mRH) in 213 cases (52.9%). Median intraoperative blood loss was 110 mL (range: 0–2092), and 7 (1.7%) received blood transfusions. Intraoperative complications occurred in 20 cases (5.0%) including ureteral injuries (1.7%), vascular injuries (1.0%), and bowel injuries (0.5%). High‐volume facilities performing more than 15 PALN procedures harvested significantly more para‐aortic nodes than facilities performing fewer procedures. Four cases (1.0%) converted to laparotomy. Postoperative complications occurred in 53 cases (13.2%), with approximately related to lymphadenectomy. Multivariate analysis identified intraoperative blood loss, number of pelvic lymph node (PLN) removed, and radical hysterectomy (RH) as risk factors for urological complications. The number of PLNs removed and mRH were associated with lymphadenectomy‐related complications. Over a median follow‐up of 14 months (1–39), 20 patients (5.0%) experienced recurrence, and 7 (1.7%) died of the disease. Conclusion Laparoscopic PALN for intermediate‐ and high‐risk endometrial cancer could be performed safely.

Interleukin-34 cancels anti-tumor immunity by PARP inhibitor

Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. We found that These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.

Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016‐A3) of the treatment strength and prognostic outcomes of conventional or dose‐dense chemotherapy

AbstractAimTo evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer.MethodsWe compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy‐seven older patients of 301 who received dose‐dense‐paclitaxel‐carboplatin (dTC) and 93 older patients of 304 who received conventional‐paclitaxel‐carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed.ResultsThe RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25–2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15–2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen.ConclusionsThe RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

Current state of fertility preservation for adolescent and young adult patients with gynecological cancer

Although the incidence of the various gynecological cancers has been increasing in recent years, long-term survival is now possible for many patients thanks to advances in multimodality treatment. When treating gynecological cancer in adolescent and young adult (AYA) patients who desire future pregnancy, it is necessary to preserve the reproductive organs and their function to prevent loss of fertility. However, because treatment targets these organs, in the large majority of cases, patients must have these organs removed. In the subfield of oncofertility, treatment of the underlying disease takes priority, and the main principle is preventing delay in treatment. Close cooperation between obstetricians and gynecologists involved in reproductive medicine and oncologists involved in cancer treatment is necessary. In addition, it is important that clinicians work closely not only with other specialists but also with such medical professionals as nurses and counselors so that cancer patients of the AYA generation can be provided the support they need to fight their cancer with hope. Herein, we describe the current status of fertility-sparing therapy for AYA patients with gynecological cancer (cervical cancer, endometrial cancer, or ovarian cancer). In addition, we explain points to keep in mind during a patient's pregnancy after fertility preservation, the latest findings on assisted reproductive technology, and the challenges and prospects of fertility preservation therapy for patients with gynecologic cancer.

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.

Immunosensitivity and specificity of insulinoma-associated protein 1 (INSM1) for neuroendocrine neoplasms of the uterine cervix

Previously, we reported that insulinoma-associated protein 1 (INSM1) immunohistochemistry (IHC) showed high sensitivity for neuroendocrine carcinoma of the uterine cervix and was an effective method for histopathological diagnosis, but that its specificity remained to be verified. Therefore, the aim was to verify the specificity of INSM1 IHC for a large number of non-neuroendocrine neoplasia (NEN) of the cervix. RNA sequences were performed for cell lines of small cell carcinoma (TCYIK), squamous cell carcinoma (SiHa), and adenocarcinoma (HeLa). A total of 104 cases of formalin-fixed and paraffin-embedded specimens, 16 cases of cervical NEN and 88 cases of cervical non-NEN, were evaluated immunohistochemically for conventional neuroendocrine markers and INSM1. All processes without antigen retrieval were performed by an automated IHC system. The transcripts per million levels of INSM1 in RNA sequences were 1505 in TCYIK, 0 in SiHa, and HeLa. INSM1 immunoreactivity was shown only in the TCYIK. Immunohistochemical results showed that 15 cases of cervical NEN showed positive for INSM1; the positivity score of the tumor cell population and the stain strength for INSM1 were high. Two of the 88 cases of cervical non-NENs were positive for INSM1 in one case each of typical adenocarcinoma and squamous cell carcinoma. The sensitivity of INSM1 for cervical NEN was 94%; specificity, 98%; the positive predictive value, 88%; and the negative predictive value, 99%. INSM1 is an adjunctive diagnostic method with excellent specificity and sensitivity for diagnosing cervical NEN. Higher specificity can be obtained if morphological evaluation is also performed.

Validation of the 2023 FIGO staging system and its concordance with the JSGO guidelines in endometrial cancer: A multi‐institutional retrospective study in Japan

Abstract Aim To validate the prognostic accuracy of the 2023 FIGO staging system and assess its alignment with the Japan Society of Gynecologic Oncology (JSGO) guidelines for endometrial cancer treatment. Methods This retrospective cohort study included 1207 patients with endometrial cancer treated at four academic hospitals in Kanagawa, Japan, between 2018 and 2022. Patients were reclassified according to the FIGO 2023 system and the JSGO recurrence risk categories. Primary endpoints included stage migration, recurrence risk (RR), overall survival (OS), and concordance between the two classification systems. Results Under FIGO 2023, the stage distribution was: I, 741 (61.4%); II, 203 (16.8%); III, 149 (12.3%); and IV, 114 (9.4%), with stage migration observed in 36.3% of cases. The FIGO 2023 system provided clearer stratification of 3‐year RR than FIGO 2009, with the RR gap widening from 80.0% to 90.1%. Sixteen patients (3.5%) with stage IA3 were classified as high risk by JSGO criteria, while 14.4% of patients considered high risk by JSGO were downstaged under FIGO 2023. Additionally, 46 patients (19.6%) with FIGO stage IA were reclassified as intermediate risk owing to focal lymphovascular space invasion (LVSI). Substantial LVSI was significantly associated with recurrence and poor prognosis (3‐year OS rates: none 94.3%, focal 89.9%, and substantial 40.7%; p  < 0.05). Molecular testing was limited: p53 in 30.2%, MSI in 5.9%, and POLE was not available. Conclusions FIGO 2023 improves prognostic precision. Incorporating LVSI extent and molecular data may refine JSGO classifications and support more individualized adjuvant therapy strategies.

Awareness and attitude toward cardio‐oncology among Japanese gynecologic oncologists in managing patients with endometrial cancer: The Japanese Gynecologic Oncology Group (JGOG) questionnaire surveys

AbstractAimThis study aimed to assess the awareness of the concept of “cardio‐oncology” and cardiovascular disease (CVD) in patients with endometrial cancer (EC) among the Japanese Gynecologic Oncology Group members.MethodsAn online anonymous survey, which consisted of questions about respondent attributes and cardio‐oncology, was conducted twice, in 2022 and 2024. During these surveys, guidelines for the treatment of uterine body neoplasm were published in July 2023.ResultsIn 2022, significantly numerous physicians were unaware of cardio‐oncology or the increased risk of developing CVD in patients with EC, and 25.3% of them answered that they had no idea about cardio‐oncology at all. However, in 2024, the percentage significantly dropped to 8.7%. The number of physicians who were aware that CVD is more common as the cause of death in patients with low‐grade EC than the cancer itself was significantly higher in 2024 than in 2022. Similarly, the number of physicians who were aware that the usage of platinum agents could become a risk factor for CVD was significantly higher in 2024. Furthermore, this study reported challenges in the collaboration between oncologists and primary care physicians in the region and in the provision of guidance for preventing metabolic syndrome.ConclusionJapanese Gynecologic Oncology Group members' awareness of cardio‐oncology was inadequate, but it seemed to be improving, especially after publishing the guideline for the treatment of uterine body neoplasm. Thus, raising awareness of cardio‐oncology and managing CVD risk in patients with EC are necessary to improve long‐term survival after cancer diagnosis.