Lymphadenectomy for the management of endometrial cancer
Abstract
Background
Endometrial carcinoma is the most common gynaecological cancer in western Europe and North America. Lymph node metastases can be found in approximately 10% of women who clinically have cancer confined to the womb prior to surgery and removal of all pelvic and para‐aortic lymph nodes (lymphadenectomy) is widely advocated. Pelvic and para‐aortic lymphadenectomy is part of the FIGO staging system for endometrial cancer. This recommendation is based on non‐randomised controlled trials (RCTs) data that suggested improvement in survival following pelvic and para‐aortic lymphadenectomy. However, treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, a systematic review and meta‐analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early‐stage endometrial cancer, did not find a survival advantage. Surgical removal of pelvic and para‐aortic lymph nodes has serious potential short and long‐term sequelae and most women will not have positive lymph nodes. It is therefore important to establish the clinical value of a treatment with known morbidity.
Objectives
To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. Cochrane Gynaecological Cancer Review Group Trials Register, MEDLINE (1966 to June 2009), Embase (1966 to June 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
Selection criteria
RCTs and quasi‐RCTs that compared lymphadenectomy with no lymphadenectomy, in adult women diagnosed with endometrial cancer.
Data collection and analysis
Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression‐free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy or no lymphadenectomy were pooled in random effects meta‐analyses.
Main results
Two RCTs met the inclusion criteria; they randomised 1945 women, and reported HRs for survival, adjusted for prognostic factors, based on 1851 women.
Meta‐analysis indicated no significant difference in overall and recurrence‐free survival between women who received lymphadenectomy and those who received no lymphadenectomy (pooled HR = 1.07, 95% CI: 0.81 to 1.43 and HR = 1.23, 95% CI: 0.96 to 1.58 for overall and recurrence‐free survival respectively).
We found no statistically significant difference in risk of direct surgical morbidity between women who received lymphadenectomy and those who received no lymphadenectomy. However, women who received lymphadenectomy had a significantly higher risk of surgically related systemic morbidity and lymphoedema/lymphocyst formation than those who had no lymphadenectomy (RR = 3.72, 95% CI: 1.04 to 13.27 and RR = 8.39, 95% CI: 4.06, 17.33 for risk of surgically related systemic morbidity and lymphoedema/lymphocyst formation respectively).
Authors' conclusions
We found no evidence that lymphadenectomy decreases the risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. The evidence on serious adverse events suggests that women who receive lymphadenectomy are more likely to experience surgically related systemic morbidity or lymphoedema/lymphocyst formation.
PICOs
Plain language summary
The role of removing lymph nodes as part of standard surgery for endometrial cancer
Cancer arising from the lining of the womb, known as endometrial carcinoma, is now the most common gynaecological cancer in western Europe and North America. Most women (75%) still have their tumour confined to the body of the womb at diagnosis and three‐quarters of women with endometrial cancer will survive for five years after diagnosis. Lymph node metastases can be found in approximately 10% of women, who clinically have cancer confined to the womb at diagnosis, and removal of all pelvic and para‐aortic lymph nodes is widely advocated, even for women with presumed early stage cancer. Lymph node removal is part in the international staging sytem (FIGO) for endometrial cancer. This recommendation is based on non‐randomised studies that suggested improvement in survival following removal of pelvic and para‐aortic lymph nodes. However, treatment of pelvic lymph nodes may not be directly therapeutic and may just indicate that a woman has a more aggressive cancer and therefore a poorer prognosis. Results of a systematic review and meta‐analysis of RCTs of routine radiotherapy to treat possible lymph node metastases in women with early‐stage endometrial cancer, did not improve survival, which was contrary to previously recommended treatment, based on evidence from non‐randomised studies. Hence, more treatment to lymph nodes might not necessarily be better treatment, especially as surgical removal of pelvic and para‐aortic lymph nodes has serious potential short and long‐term harmful effects and most women will not have positive lymph nodes.
We found only two trials that compared lymphadenectomy with no lymphadenectomy in women with endometrial cancer. These two trials enrolled 1945 women. When we combined the findings from these two trials, we found that there was no evidence that women who received lymphadenectomy were less likely or more likely to die or have a relapse of their cancer. There were a considerable number of deaths and disease recurrences in the trials. Kitchener 2009 reported 191 deaths and 173 disease recurrences; Panici 2008 reported 53 deaths and 78 disease recurrences, so the estimates are likely to be accurate. The uncertainty of whether lymphadenectomy or no lymphadenectomy is best probably reflects the fact that there is no benefit in undertaking lymphadenectomy, rather than a lack of statistical power to detect a difference. More women experienced severe adverse events as a consequence of lymphadenectomy than those having no lymphadenectomy. The main limitations of the review were that we did not find any trials that evaluated either pelvic lymph node sampling, pelvic and para‐aortic lymphadenectomy or the removal of bulky pelvic lymph nodes and the fact that quality of life (QOL) was not reported in either trial. The QOL for women following treatment is especially important for a condition that has relatively good survival rates.
