The role of lymphadenectomy in endometrial cancer

The role of lymphadenectomy in the management of endometrial cancer is rapidly evolving. Although retrospective reports have suggested that lymphadenectomy is associated with a therapeutic benefit, recent prospective trials have questioned the therapeutic effect of lymphadenectomy. Lymphadenectomy remains the gold standard for detecting metastatic disease to the regional nodes. In this review, we discuss the controversies surrounding lymphadenectomy for endometrial cancer.     

Current indications of lymphadenectomy in endometrial cancer

Endometrial cancer is a tumor associated with a good prognosis as it is often diagnosed at an early stage. Up to 20 % of patients with stage I disease have a nodal involvement. Knowledge of nodal status provides important prognostic information. As preoperative assessment yields a poor value, prognostic lymphadenectomy appears to be indicated. However, therapeutic benefit of pelvic and para-aortic lymphadenectomy remains controversial. Recent randomized trials did not find any impact on survival for patients with low risk of nodal involvement. Thus, lymphadenectomy should no more be systematically performed in this low risk group. Nevertheless, pelvic and para-aortic lymphadenectomy seems to have a benefit in the high risk group, as isolated involved para-aortic nodes have been described.     

Pelvic lymphadenectomy in high risk endometrial cancer

Two hundred and thirty-eight out of a total of 1012 patients with 'high risk' endometrial cancer underwent a complete pelvic lymphadenectomy. When the disease was confined to the corpus, the rate of node positivity was 7%, when the cervix was involved it was 22% and with adnexal involvement was 52%. The recurrence rate with negative nodes was 14% compared to 45% with positive nodes. Age, menopausal status, histology and depth of invasion were predictors of survival after stratification by node status. Node status had no significant influence on site of recurrence. Women who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy (TAH-BSO) and pelvic lymphadenectomy followed by vaginal vault brachytherapy had a similar cancer-free survival to those treated by TAH-BSO alone, followed by adjuvant megavoltage therapy and vaginal vault brachytherapy.     

子宫内膜癌淋巴结切除适应证和争议

早期子宫内膜癌有淋巴转移风险,但是否对所有患者均需行区域淋巴结切除仍有争议。可根据术前、术中的评估决定是否行淋巴结切除及何种范围的淋巴结切除。高危病例应该实施系统性淋巴结切除。     

Laparoscopic lymphadenectomy as treatment of endometrial cancer

AIM: This study compares the effects of laparoscopic lymphadenectomy versus those of abdominal lymphadenectomy in patients with endometrial cancer. METHODS: A prospective randomized study was performed among 80 patients randomly assigned to laparoscopic lymphadenectomy and to abdominal lymphadenectomy in the treatment of endometrial cancer. Clinical outcomes and complications were compared for 1 year of follow-up. RESULTS: Forty patients were assigned to laparoscopic lymphadenectomy and 40 patients to abdominal lymphadenectomy. The laparoscopic approach was associated with a longer operative time (234.1 min vs 137.3 min) but was less painful (VAS 5.3 vs 7.9; P<0.000) and resulted in a shorter hospital stay (4.4+/-1 vs 7.9+/-1.2 days; P<0.000). At 6 weeks the quality of life was better in patients who had laparoscopic lymphadenectomy (SF-12). CONCLUSION: Laparoscopic lymphadenectomy was associated with a significantly lower rate of major and minor postoperative complications and a better short term quality of life.     

Role of pelvic lymphadenectomy in the management of stage I endometrial cancer: our experience

OBJECTIVES: To estimate the prognostic value of pelvic-node removal on survival of patients affected by endometrial carcinoma at presurgical FIGO Stage I. METHODS: A retrospective analysis was performed on a total of 111 patients recruited from 1990 to 1996 at the S. Carlo di Nancy Hospital. Thirty-nine (35%) of them underwent a total hysterectomy and bilateral salpingo-oophorectomy with removal of the vaginal cuff (group 1), while 72 (65%) underwent a total hysterectomy combined with pelvic lymphadenectomy (group 2). Prognostic features including tumor grade, depth of myometrial invasion and histologic subtype. Survival rates were calculated with Cox and Kaplan analyses. RESULTS: Overall survival rate at five years was 91.2%. The survival rate of group 1 and group 2 was 89% and 92.8%, respectively which is not statistically significant. Stage, grade, histotype, age at diagnosis, and presence of positive lymph nodes did not show any significant prognostic value on survival probability. CONCLUSIONS: The survival rate for patients submitted to lymphadenectomy (group 2) was the same of patients who did not undergo this treatment (group 1). Nevertheless, pelvic lymphadenectomy in endometrial carcinoma at presurgical FIGO stage I was worthwhile as it allowed correct staging to be performed. The prediction of nodal disease based only on preoperative investigations (such as TC, NMR) is often inaccurate.     

Role of lymphadenectomy in ovarian cancer

The exact role of lymphadenectomy in the management of ovarian cancer has been the object of controversy during recent years. The International Federation of Obstetrics and Gynecology has indicated that pelvic and para-aortic lymph node sampling is an integral part of the staging system of ovarian cancer. On the other hand the advantage of systematic sampling, resection of bulky nodes only, or no lymphadenectomy in terms of recurrence rate and survival of ovarian cancer patients has not yet been clearly defined. Thanks to the analysis of clinical studies on systematic lymphadenectomy, detailed anatomical studies to assess the location of lymph nodes and lymphatic spread have been recently reported.In this chapter we report the available data on clinical anatomy and pathological assessment of lymph node and lymphatic spread of ovarian cancer metastasis; we also review the clinical data on correlation of lymph node metastasis and disease status. Surgical techniques developed during years of dedication to this procedure are also described. Finally, we review and discuss the actual benefits of lymph node dissection in patients with ovarian cancer, analysing previously reported and ongoing trials.     

High throughput silencing identifies novel genes in endometrioid endometrial cancer

Objective

To validate the gene expression profile obtained from the previous microarray analysis and to further study the biological functions of these genes in endometrial cancer. From our previous study, we identified 621 differentially expressed genes in laser-captured microdissected endometrioid endometrial cancer as compared to normal endometrial cells. Among these genes, 146 were significantly up-regulated in endometrial cancer.

Clinical value of immunohistochemically detected lymphovascular invasion in endometrioid endometrial cancer

INTRODUCTION: Lymphovascular Invasion (LVSI) of tumour cells is marked as an important step in the process of tumour metastases and is an important prognostic factor in Endometrial Cancer (EC). Currently, the standard method for assessing LVSI is light microscopic examination of H&E stained sections. Tumour cells within lymphovascular spaces can evade detection on H&E staining if they are present in very small numbers or surrounded by a greater number of circulating cells. Dual immunostaining for epithelial and endothelial cell markers cell markers has been shown to increase detection rate of LVSI significantly. OBJECTIVES: To investigate the clinical significance of LVSI as detected by H&E (LVSI-H&E) and immunohistochemically (LVSI-IHC) in clinically stage I endometrioid EC patients. Methods. Single representative section of 90 patients with stage I endometriod EC were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal pancytokeratin (PCK), clone AE1/AE3 and CD31 endothelial cell marker. The H&E sections and their corresponding immunostained sections were re-examined to identify LVSI. Clinical records were available on 72 patients. The following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes and hypertension), use of Tamoxifen or HRT, menopausal state, recurrence and survival. RESULTS: Overall, LVSI was present in 45 (50%) cases and absent in 45 (50%) cases on IHC, as compared with 17 (19%) and 73 (81%) cases, respectively, on H&E. Statistical analysis revealed significant association between LVSI-H&E and depth of myometrial invasion (P < 0.0001). The median follow-up period was 161 months (range 5-207 months). During the follow-up period, six of 14 cases with evidence of LVSI-H&E presented with recurrence as opposed to six of 58 patients with no evidence (OR = 6.26, 95%: CI = 1.3-30.6). There was a significant association between tumour recurrence rate and LVSI-H&E (P = 0.01). The 5-year recurrence-free survival was 54% for the group with H&E evidence of LVSI (95%: CI = 44-64%) compared with 89% for the group without (95%: CI = 82-97%). There was a significant difference in the recurrence-free survival between the two groups (Chi-square = 6.96, P = 0.008). In contrast, LVSI-IHC was found to be significantly associated only with high-grade tumours (P = 0.01) and survival analysis revealed no statistically significant association with recurrence or survival. CONCLUSIONS: LVSI-H&E in stage I EC remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event, associated with tumour grade and appears to be of no statistically significant clinical value.     

Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer

OBJECTIVE: The aim of this study was to assess the potential therapeutic role of para-aortic lymphadenectomy (PAL) in high-risk patients with endometrial cancer. METHODS: We studied two groups of patients with endometrial cancer who underwent operation at Mayo Clinic (Rochester, MN) during the interval 1984 to 1993: (1) 137 patients at high risk for para-aortic lymph node involvement (myometrial invasion >50%, palpable positive pelvic nodes, or positive adnexae), excluding stage IV disease, and (2) 51 patients with positive nodes (pelvic or para-aortic), excluding stage IV disease. By our definition, PAL required removal of five or more para-aortic nodes. RESULTS: In both groups, no significant difference existed between patients who had PAL (PAL+) and those who did not (PAL-) in regard to clinical or pathologic variables, percentage irradiated, or surgical or radiation complications. Among the 137 high-risk patients, the 5-year progression-free survival was 62% and the 5-year overall survival was 71% for the PAL- group compared with 77 and 85%, respectively, for the PAL+ group (P = 0.12 and 0.06, respectively). For the 51 patients with positive nodes, the 5-year progression-free survival and 5-year overall survival for the PAL- group were 36 and 42% compared with 76 and 77% for the PAL+ group (P = 0.02 and 0.05, respectively). Lymph node recurrences were detected in 37% of the PAL- patients but in none of the PAL+ patients (P = 0.01). Multivariate analysis suggested that submission to PAL was a cogent predictor of progression-free survival (odds ratio = 0.25; P = 0.01) and overall survival (odds ratio = 0.23; P = 0.006). CONCLUSIONS: These results suggest a potential therapeutic role for formal PAL in endometrial cancer.     

Clinical value of pelvic lymphadenectomy in surgical treatment of endometrial cancer

OBJECTIVES: The aim of the study was the clinical analysis of value of pelvic lymphadenectomy in surgical treatment of endometrial carcinoma. MATERIAL AND METHODS: The group of 420 women treated for of endometrial cancer in stage IA-IV by FIGO 1988 was analysed. All these women were operated in 2nd Dept. of Obstetrics and Gynecology Medical University of Gdańsk between 1981-2000. The subgroup of patients with pelvic lymphadenectomy was selected. The data were obtained from case histories. RESULTS: The subgroup of patients on whom pelvic lymphadenectomy was performed was up 32.6% of all treated women (137 women). Neoplastic metastases were found in 27 cases (19.7%). All those patients were in clinical stage II-IV by FIGO 1988, and no earlier stage of endometrial cancer was found in that group. In every case myometrial invasion was more then 1/2 of myometrium. In 59.2% of neoplastic metastases high or medium differential adenocarcinoma were found. CONCLUSION: Pelvic lymphadenectomy has to be part of surgical treatment of endometrial cancer. Lymph nodes metastases are important prognostic factors. Myometrial invasion plays an important role as a risk factor of lymph nodes metastases.     

Prospective evaluation of the morbidity of complete lymphadenectomy in endometrial cancer

Fanning S, Firestein S. Prospective evaluation of the morbidity of complete lymphadenectomy in endometrial cancer. Int J Gynecol Cancer 1998; 8 : 270–273.
The purpose of this study is to prospectively evaluate the morbidity of complete lymphadenectomy in endometrial cancer. Eighty consecutive eligible patients with endometrial cancer underwent surgical staging consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, complete bilateral pelvic lymphadenectomy, and aortic lymphadenectomy. We prospectively evaluated operative time, blood loss, and morbidity of lymphadenectomy.
The median number of pelvic lymph nodes resected was 21 and aortic lymph nodes was 7. Median time of lymphadenectomy was 24 min. Median blood loss from lymphadenectomy was < 25 cc. There was one complication from lymphadenectomy. We conclude that, in this prospective study, complete pelvic and aortic lymphadenectomy in the surgical staging of endometrial cancer was performed quickly, with minimal blood loss and morbidity. In endometrial carcinoma surgical staging, the majority of operative time, blood loss, and morbidity is secondary to hysterectomy/oophorectomy rather than lymphadenectomy.     

Prognostic factors determining survival after extrapelvic recurrence in endometrioid type endometrial cancer

ObjectiveTo define the factors that determine survival after extrapelvic recurrence in patients with endometrioid type endometrial cancer (EC).objectiveMaterials and methodsClinicopathological and survival data of surgically treated endometrioid type EC patients who recurred outside pelvis were reviewed. Patients who had non-endometrioid tumor, sarcomatous component in the final pathology and synchronous tumor were excluded. The period from surgery to recurrence was defined as time to recurrence (TTR) and the period from recurrence to death or last visit was defined as post-recurrence survival (PRS).ResultsSixty-six patients with extrapelvic recurrence were included in the study. No residual disease was achieved in all patients at initial surgery. Median TTR was 18 months (range, 2–84). Recurrence developed within 1 year in 24 (36.4%) patients and between 13 and 24 months in 22 (33.3%) patients. Fifty-three of 66 patients (80.3%) had extraabdominal recurrence. The 2-year PRS of the all cohort with extrapelvic recurrence was 56%. In the univariate analysis, advanced FIGO stage, lymph node metastasis, adnexal metastasis and short TTR were associated with diminished PRS (p < 0.05). The salvage chemotherapy for recurrence had a tendency to be associated with improved PRS in the univariate analysis. Two-year survival was 81% and 37% in the patients who received chemotherapy and radiotherapy, respectively (p = 0.057).ConclusionAlmost half of the patients with extrapelvic recurrence died of disease within 2 years. Chemotherapy seemed to be more effective than radiotherapy as the salvage therapy of extrapelvic recurrences.     

Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients

OBJECTIVE: To assess the efficacy of systematic lymphadenectomy and adjuvant radiotherapy in minimizing pelvic sidewall and para-aortic failures. METHODS: Between January 1984 and December 2001, a total of 146 patients with stage III and IV endometrial cancer and lymph node metastases were treated at our institution. Adequate pelvic lymphadenectomy was defined as the removal of more than 10 pelvic lymph nodes, and adequate para-aortic lymphadenectomy was defined as removal of 5 or more para-aortic lymph nodes. The 24 patients who received adjuvant chemotherapy were excluded. We assessed the ability of adequate pelvic and para-aortic lymphadenectomy, together with radiotherapy, to prevent pelvic and para-aortic recurrences. RESULTS: Of the 122 patients studied, 94 (77%) had adequate pelvic lymphadenectomy and 47 (39%) had adequate para-aortic lymphadenectomy. Pelvic radiotherapy was administered to 78% and para-aortic radiotherapy to 29% of patients. Median follow-up of censored patients was 56 months. Twenty-five percent of patients had pelvic sidewall failure at 5 years. Pelvic sidewall failures at 5 years occurred in 57% of patients who had inadequate node dissection and/or no radiotherapy, compared with 10% for those having both adequate lymphadenectomy and radiotherapy (P < 0.001). After risk factor assessment in a regression model, only treatment with adequate lymphadenectomy and radiotherapy was a significant independent predictor of pelvic control (P = 0.03). The performance of definitive pelvic lymphadenectomy may have increased treatment-related morbidity in the subgroup of patients who had postoperative radiotherapy. For the 41 patients with positive para-aortic lymph nodes, the 5-year para-aortic failure rate was 34% after adequate lymphadenectomy but without adjuvant para-aortic radiotherapy. Likewise, 69% failed in the para-aortic area when adjuvant para-aortic radiotherapy was administered to patients not having adequate para-aortic lymphadenectomy; however, none of the 11 patients failed in the para-aortic area after adequate lymphadenectomy and para-aortic radiotherapy (P = 0.08). CONCLUSIONS: Adequate (pelvic and para-aortic) lymphadenectomy and adjuvant radiotherapy appear complementary in reducing failures in both the pelvis and para-aortic areas in patients with node-positive endometrial cancer.     

Role of diet in endometrial cancer patients

The hypothesis of a correlation between diet and cancer is widely supported by several epidemiological and experimental studies. Certainly the exact mechanism of this intervention is still unknown; nevertheless in the tests of a carcinogenesis the direct action of some food is recognised, whereas the indirect action of others should occur through modifications of immune and endocrine systems. Many studies conclude that a high intake of fats and animal proteins appeared to be associated with the etiology of some endocrine related neoplasms, such as the cancer of prostate breast endometrium and ovary. We studied the dietary practices and some constitutional parameters of women affected by endometrial cancer and control women. We did not find a significant difference between the two groups related to height. Conversely the daily intake of lipids and particularly of proteins, glucides and calories turned out much higher in the group of patients. Moreover we found a significant difference related to weight; obese women were more numerous in the group of patient. The above results confirm the importance of a right diet in the prevention of this neoplasm.