Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials.

PURPOSE: The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer. METHODS: A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location. RESULTS: Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA. CONCLUSION: Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

Proposal of a concept and design of a randomized phase III trial investigating the survival effect of para-aortic lymphadenectomy in endometrial cancer.

Although prospective studies have failed to show the therapeutic effect of lymphadenectomy in the surgical treatment of endometrial cancer, several retrospective studies including the SEPAL study revealed the survival effect of lymphadenectomy. To prospectively investigate the survival benefit of para-aortic lymphadenectomy shown in the SEPAL study, we are proposing a new concept of a randomized phase III trial. An appropriate study population will be selected according to the preoperative assessments (evaluation of myometrial invasion and cervical invasion with magnetic resonance imaging, extrauterine spread with computed tomography, and histological type and grade by pathological evaluation) to estimate the risk of lymph node metastasis. Patients relevant to potential International Federation of Gynecology and Obstetrics (2008) stage IB, II and III diseases will be eligible, and randomly assigned to two arms: pelvic lymphadenectomy alone (control), or pelvic and para-aortic lymphadenectomy (experimental). After initial surgery, patients with postoperative pathological risk factors for recurrence will receive adjuvant chemotherapy. Because we aim to investigate the therapeutic significance of primary treatments, including surgery and adjuvant chemotherapy, the primary end-point could be recurrence-free survival. One of the most important issues to successfully perform this prospective study is to assure the quality of lymphadenectomy (extent and area), which could be evaluated based on the number of harvested nodes and objective evaluation of dissected area by videos and/or photos.

A low-risk group for lymph node metastasis is accurately identified by Korean gynecologic oncology group criteria in two Japanese cohorts with endometrial cancer.

OBJECTIVE: The Korean Gynecologic Oncology Group (KGOG) recently proposed new pre-operative criteria to identify a low-risk group for lymph node metastasis in endometrial cancer. The aim of this study was to test whether the good performance of the criteria can be reproducible in diverse clinical settings. METHODS: From two Japanese hospitals, 319 patients with endometrial cancer who underwent systemic lymphadenectomy were retrospectively reviewed. In one hospital, para-aortic lymphadenectomy was routinely performed, but it was selectively performed in the other hospital. The performance of the criteria was determined by adjusting the false-negative rate (FNR) at the given prevalence of nodal metastasis of 10% using Bayes' theorem. RESULTS: Nodal metastasis rate of the study population was 12.9%. The KGOG low-risk criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). Despite a significant difference in the nodal metastasis rate (18.2% and 8.8%, P=.012) and the surgical policy for para-aortic lymphadenectomy (100% and 48.9%, P<.001) between the two hospitals, KGOG criteria consistently showed a very low adjusted FNR at the prevalence of 10% in both hospitals (1.8% vs. 1.1%, respectively). Among the entire study population, the adjusted FNR was 1.4% (95% confidence interval, .5% to 4.3%), which was similar to the FNR of 1.3% in our previous study. CONCLUSION: The KGOG low-risk criteria accurately identified a low-risk group for lymph node metastasis with acceptable false negativity regardless of diverse clinical settings.

New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the stage migration and survival of endometrial cancer by the revised FIGO 2008 staging system compared with the 1988 staging system. METHODS: A total of 355 patients with endometrial cancer, who underwent complete surgical staging, were enrolled. We compared the surgical stages and survival by FIGO 1988 staging system with those by FIGO 2008 staging system. RESULTS: 2008 FIGO staging system resulted in an increase of stage I patients and decrease of stage II and IIIa patients. The 5-year overall survival (OS) rates for patients with 2008 FIGO stage IA and IB disease were 98.2% and 91.9%, respectively (P = 0.004). Five-year OS rate of new stage II (82.6%) was significantly worse than that of new stage IA (98.2%, P = 0.003). Patients with positive washing cytology alone revealed a 5-year OS rate similar to that of patients with new stage IIIA disease (96.2% vs. 90.9%, respectively; P = 0.53). The 5-year OS rate for patients with stage IIIC1 disease was improved compared with that for patients with stage IIIC2 disease (85.7% vs. 63.0%, respectively; P = 0.08). CONCLUSION: New revised FIGO 2008 staging system for endometrial cancer produced better discrimination in OS outcomes compared with the 1988 system.

Clinical efficacy of paclitaxel/cisplatin as an adjuvant chemotherapy for patients with cervical cancer who underwent radical hysterectomy and systematic lymphadenectomy.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the clinical efficacy of paclitaxel/cisplatin (TP) as an adjuvant chemotherapy to adjuvant radiotherapy (RT) after radical hysterectomy and systematic lymphadenectomy for patients with cervical cancer. METHODS: A total of 125 patients with early-stage cervical cancer, who underwent radical hysterectomy, and received adjuvant therapy due to recurrent risk factors were retrospectively analyzed. Forty-nine patients were treated with RT, and 32 received paclitaxel/cisplatin (TP) for three to six cycles at 4-week interval. Survival and postoperative complications were compared between two modalities. RESULTS: There was no significant difference of 3-year disease-free survival between two groups (P = 0.23), while significantly better 3-year overall survival in TP group than RT group (P = 0.02). Seven of 32 patients (21.9%) treated with adjuvant TP, 16 of 49 patients (32.7%) treated with RT showed disease recurrence. Median of survival time after recurrence in RT group and TP group was 8.5 months, 12.0 months, respectively. Postoperative bowel obstruction was significantly more frequent in the RT group compared to the TP group (P = 0.01). CONCLUSIONS: Postoperative chemotherapy using TP might be more beneficial for survival than adjuvant RT and can reduce postoperative complications for cervical cancer patients treated with radical hysterectomy.

Multivariate survival analysis of the patients with recurrent endometrial cancer.

OBJECTIVE: Few studies on the prognosticators of the patients with recurrent endometrial cancer after relapse have been reported in the literature. The aim of this study was to determine the prognosticators after relapse in patients with recurrent endometrial cancer who underwent primary complete cytoreductive surgery and adjuvant chemotherapy. METHODS: Thirty-five patients with recurrent endometrial cancer were included in this retrospective analysis. The prognostic significance of several clinicopathological factors including histologic type, risk for recurrence, time to relapse after primary surgery, number of relapse sites, site of relapse, treatment modality, and complete resection of recurrent tumors were evaluated. Survival analyses were performed by Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. RESULTS: Among the clinicopathological factors analyzed, histologic type (p=0.04), time to relapse after primary surgery (p=0.03), and the number of relapse sites (p=0.03) were significantly related to survival after relapse. Multivariate analysis revealed that time to relapse after primary surgery (hazard ratio, 6.8; p=0.004) and the number of relapse sites (hazard ratio, 11.1; p=0.002) were independent prognostic factors for survival after relapse. Survival after relapse could be stratified into three groups by the combination of two independent prognostic factors. CONCLUSION: We conclude that time to relapse after primary surgery, and the number of relapse sites were independent prognostic factors for survival after relapse in patients with recurrent endometrial cancer.

Survival and prognosticators of node-positive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy.

OBJECTIVE: Lymph node metastasis (LNM) is known to be the most important prognostic factor in cervical cancer. We analyzed the number of positive lymph nodes and other clinicopathological factors as prognostic factors for survival in node-positive patients with cervical cancer. METHODS: Node-positive cervical cancer patients (n = 108) who underwent radical hysterectomy and systematic lymphadenectomy in Hokkaido University Hospital from 1982 to 2002 were enrolled. Clinicopathological data including age, stage, histologic subtype, and the number of LNM sites were collected. The main outcome was the overall survival (OS) rate for Stage Ib-IIb patients treated with surgery and postoperative radiotherapy. RESULTS: The 5-year OS rate of patients with 1 positive node was 93.3%, that for 2 nodes was 77.3%, for 3 nodes it was 33.3%, and for 4 or more it was 13.8%. The OS rate of patients with 1 or 2 LNM sites was significantly better than that for patients with more than 2 LNM sites. The OS rate of patients with adenocarcinoma (Ad) (28.6%) was significantly lower than that for patients with other histologic subtypes (squamous cell carcinoma; 66.7%, adenosquamous carcinoma; 75.0%, p = 0.0003). Multivariate analysis revealed that >2 LNM sites and Ad were independent prognostic factors for survival. The 5-year OS rate of patients with 1 or 2 LNM sites was 86.8%, a more favorable prognosis than the OS rates in other reports. CONCLUSION: More than two LNM sites and adenocarcinoma were independent prognostic factors for node-positive patients with cervical cancer.