Systematic pelvic and paraaortic lymphadenectomy failed to improve survival among women with advanced ovarian cancer who underwent macroscopically complete resection and had normal lymph nodes before and during surgery, according to results from the randomized LION trial published in The New England Journal of Medicine.
Lymphadenectomy instead appeared associated with a higher rate of postoperative complications than no lymphadenectomy among this patient population.
“Many of the retrospective analyses including large numbers of patients have suggested a benefit of lymphadenectomy and, accordingly, patients have been exposed to this procedure over the decades,” Philipp Harter, MD, PhD, of the department of gynecology and gynecologic oncology at Kliniken Essen-Mitte in Germany, and colleagues wrote. “However, evaluations of lymphadenectomy as compared with no lymphadenectomy in nonrandomized studies are prone to several biases.”
In the prospectively randomized, controlled LION trial, researchers evaluated 647 women aged 21 to 83 years (median age, 60 years) with newly diagnosed, advanced epithelial ovarian cancer who underwent macroscopically complete tumor resection and presented with normal lymph nodes before and after surgery. The researchers randomly assigned women to lymphadenectomy (n = 323) or no lymphadenectomy (n = 324) between December 2008 and January 2012. All participating centers had to meet surgical quality criteria to be included in the trial.
OS served as the primary endpoint. Secondary endpoints included PFS, quality of life and number of resected lymph nodes.
The surgeons removed a median of 57 nodes (35 pelvic and 22 paraaortic) from women who underwent lymphadenectomy.
Results showed median OS of 69.2 months in the no-lymphadenectomy group vs. 65.5 months in the lymphadenectomy group (HR for death in the lymphadenectomy group = 1.06; 95% CI, 0.83-1.34).
Both groups achieved median PFS of 25.5 months (HR for progression or death in the lymphadenectomy group =1.11; 95% CI, 0.92-1.34).
Women in the lymphadenectomy group more frequently incurred serious postoperative complications than those in the non-lymphadenectomy group, including repeat laparotomy (12.4% vs. 6.5%; P = .01) and mortality within 60 days after surgery (3.1% vs. 0.9%; P = .049).
The researchers did not observe clinically meaningful differences in global health status or subdomains of quality of life between the groups.
“The results of this prospectively randomized, adequately powered, international, multicenter trial add level 1 evidence to the long-standing discussion about the role of lymphadenectomy in advanced ovarian cancer and once more underline the importance of the use of proper research methods in generating clinical evidence,” the researchers wrote.
The trial, with its novel design, has provided clarity regarding the use of systematic lymphadenectomy, Eric L. Eisenhauer, MD, chief of oncologic gynecology at Massachusetts General Hospital, and Dennis S. Chi, MD, deputy chief of the gynecology service at Memorial Sloan Kettering Cancer Center, wrote in a related editorial.
“The procedures required to achieve complete cytoreduction already have attendant risks, and eliminating ineffective techniques such as systematic lymphadenectomy is prudent to improve patients’ overall recovery,” they wrote. “Along the way, we may also have learned a bit about how difficult it can be to overcome our assumptions without a properly controlled trial design.” – by Jennifer Byrne
Disclosures: Harter reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Eisenhauer reports nonfinancial and other support from Clovis Oncology, Covidien, Janssen Biotech, Tesaro and Transenterix outside the submitted work. Chi reports personal fees and other support from Bovie Medical Co., CSurgeries and Verthermia Inc., and other support from Intuitive Surgical Inc. outside the submitted work.