The conclusions of the SEPAL study are published Online First. It reports that 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. 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. The findings are relevant for patients at medium to high risk of cancer recurrence. Therefore, the complete procedure should be recommended to these patients. The article is the work of Professor Noriaki Sakuragi and Dr Yukiharu Todo, Department of Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, and colleagues.

Earlier research has shown there is no therapeutic benefit of pelvic lymphadenectomy for endometrial cancer. The authors aimed in this new study, 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.

A total of 671 patients were involved in the SEPAL study. They had 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 centers in Japan (January, 1986 to June, 2004). Adjuvant radiotherapy or chemotherapy was offered to patients at intermediate or high risk of recurrence. The primary outcome measure was overall survival.

Findings indicated 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. However in low-risk patients, overall survival was not linked to lymphadenectomy type. In patients with intermediate or high risk of recurrence, the complete procedure reduced the risk of death compared with pelvic lymphadenectomy by 56 percent. The analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy reported that risk of death decreased with the complete procedure by 52 percent. With adjuvant chemotherapy it decreased by 41 percent, independently of one another.

The authors comment: “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 write in conclusion: “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 associated remark, Dr Sean C Dowdy, and Dr Andrea Mariani, Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA, concur with the authors. The SEPAL results now need validating with a randomized controlled trial.

They say in closing: “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.”

“Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis”
Yukiharu Todo, Hidenori Kato, Masanori Kaneuchi, Hidemichi Watari, Mahito Takeda, Noriaki Sakuragi
DOI: 10.1016/S0140-6736(09)62002-X
The Lancet

Written by Stephanie Brunner (B.A.)