Public Release: 

More complete removal of lymph nodes improves survival in endometrial cancer (SEPAL study)

Lancet

A complete, systematic removal of both pelvic lymph nodes (lymphadenectomy) and para-aortic lymph nodes*, improves survival compared with removal of just the pelvic lymph nodes, in patients at medium to high risk of cancer recurrence. Thus the complete procedure should be recommended to these patients. These are the conclusions of the SEPAL study, published Online First and written by Professor Noriaki Sakuragi and Dr Yukiharu Todo, Department of Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, and colleagues.

Previous studies have shown that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer. In this new study, the authors aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence.

The SEPAL study involved 671 patients with endometrial cancer who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986-June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival.

The researchers showed that risk of death in the complete procedure group was around half that in the pelvic lymphandecotomy only group. This association was also recorded in 407 patients at intermediate or high risk or cancer recurrence, but overall survival was not related to lymphadenectomy type in low-risk patients. In patients with intermediate or high risk of recurrence, the complete procedure reduced the risk of death compared with pelvic lymphadenectomy by 56%. Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that risk of death decreased with the complete procedure by 52%, and with adjuvant chemotherapy by 41%, independently of one another.

The authors say: "Findings from the SEPAL study have shown that para-aortic lymphadenectomy has survival benefits for patients at intermediate or high risk of recurrence, and that pelvic lymphadenectomy alone might be an insufficient surgical procedure for endometrial cancer in patients at risk of lymph node metastasis. The results also suggest that adjuvant chemotherapy could further improve survival of patients at high risk of lymph node metastasis."

They conclude: "Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high-risk of recurrence."

In an accompanying Comment, Dr Sean C Dowdy, and Dr Andrea Mariani, Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA, agree with the authors that the SEPAL results now need validating with a randomised controlled trial.

They conclude: "Such a trial should also examine differences in morbidity, cost, and quality of life, all of which previous studies have failed to address. Disease-specific survival is but one of many important endpoints because patients will often succumb to other comorbidities. Only by consideration of such factors will a standard of care be identified for the surgical treatment of endometrial cancer. Such a standard is long overdue."

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Professor Noriaki Sakuragi, Department of Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. T) +81 117065938 E) sakuragi@med.hokudai.ac.jp

Dr Sean C Dowdy, and Dr Andrea Mariani, Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA. E) dowdy.sean@mayo.edu

For full Article and Comment, see: http://press.thelancet.com/sepal.pdf

Note to editors: *The para-aortic lymph nodes are a group of lymph nodes that lie in front of the lumbar vertebral bodies near the aorta. These lymph nodes receive drainage from the lower gastrointestinal tract and the pelvic organs.

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