Toru Nakanishi

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180 mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0 years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1 months (95% CI 6.5-11.9), while the median overall survival time was 23.2 months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Prognostic significance of para-aortic node metastasis in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis

This study aimed to assess the prognostic significance of para-aortic lymphadenectomy (PALX) and para-aortic lymph node metastasis in endometrial cancer (EC) patients at risk of post-operative recurrence. Japanese Gynecologic Oncology Group (JGOG) 2043 was a randomized controlled trial assessing the efficacy of adjuvant chemotherapy in EC patients at risk for post-operative recurrence. A retrospective analysis included patients who underwent pelvic lymphadenectomy (PLX) alone or both PLX and PALX in JGOG2043. Data on positive lymph nodes and other clinicopathological risk factors were collected. PLX and PALX were performed on 402 patients, while PLX alone was conducted on 250 patients. Evaluating the effect of PALX on survival was challenging through a comparison of the outcomes of the 2 cohorts since PALX was predominantly administered to higher-risk patients. Patients with 2 or more metastases in para-aortic nodes exhibited significantly poorer overall survival than those with no or 1 metastasis, respectively (p<0.001, p=0.031). Multivariate analysis revealed that 2 or more metastases in para-aortic nodes is independent risk factors for disease-free survival (hazard ratio [HR]=1.72; 95% confidence interval [CI]=1.10-2.72; p=0.019) and are marginally significant for overall survival (HR=1.58; 95% CI=0.92-2.72; p=0.096) compared to no or a single metastasis. The clinical relevance of PALX was challenging to evaluate in the JGOG2043 cohort; however, the presence of 2 or more para-aortic node metastases was identified as an independent unfavorable prognostic factor in EC patients at risk of recurrence.

Prognostic impact of the number of resected pelvic nodes in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis

This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients' backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24-0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.