By Gene Emery
(Reuters Health) - 27/2/2019
Women with advanced ovarian cancer and normal lymph nodes after complete resection experience no survival benefit from systematic pelvic and paraaortic lymphadenectomy, a randomized study of 647 volunteers has concluded.
Median overall survival was 65.5 months with lymphadenectomy versus 69.2 months in women who didn't undergo the procedure (P=0.65), according to results published online February 27 in The New England Journal of Medicine.
Median rates of progression-free survival in the two groups were identical, at 25.5 months.
Yet the surgery more than tripled the 60-day mortality rate and nearly doubled the odds of serious postoperative complications.
"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," said the authors, led by Dr. Philipp Harter of Kliniken Essen-Mitte in Germany.
"Now there is good evidence that it does not help and that it carries added risk of post-operative problems," said Dr. Steven Waggoner, a professor in the department of reproductive biology at Case Western Reserve University School of Medicine, who was not involved in the research.
He predicted in a telephone interview with Reuters Health that use of the surgery "will be far, far less within the next year in this country based on this report. The surgery doesn't seem to make a difference in cancer-related outcomes."
The new test "effectively shows that systematic removal of these lymph nodes after maximal cytoreduction does not improve survival and may cause additional harm," echoed Drs. Eric Eisenhauer and Dennis Chi in a Journal editorial. They said the design of the study, known as LION, "resolved the criticisms of many previous studies" that have failed to settle the controversy over the wisdom of the surgery.
About 22,530 cases of ovarian cancer will be diagnosed in the United States this year and 13,980 women will die from their tumors, according to estimates from the American Cancer Society.
All of the women in LION had FIGO stage IIB through IV advanced epithelial ovarian cancer. If the tumor had spread beyond the peritoneal cavity, only patients with resectable metastases in the liver, spleen, abdominal wall or pleura were included. All the volunteers had a good Eastern Cooperative Oncology Group performance status of 0 or 1 on the 6-point scale. They were treated at 52 centers in Europe where doctors were screened for proficiency in the surgery.
Eligibility also required macroscopically complete resection. Only 650 of the 1,895 patients screened for the trial met the criteria to be randomized.
Ultimately, 55.7% of the women in the node-removal group were found to have positive nodes.
"What that tells me is that even leaving microscopic disease in the lymph nodes in people you know are going to get additional treatment does not have an adverse effect on their prognosis," said Dr. Waggoner.
The additional surgery added 60 minutes to the operation time and an addition blood loss of 150 ml. All of the lymphadenectomy patients received a transfusion or fresh-frozen plasma, versus 277 of 323 (86%) in the control group.
Serious postoperative complications occurred at a rate of 12.4% with the additional surgery and 6.5% without (P=0.01). The 60-day death rate was 3.1% with lymphadenectomy and 0.9% without (P=0.049).
Infection rates were 25.8% with the extra surgery and 18.6% without.
Dr. Waggoner said the results should be considered in the context that a lot has changed in the treatment of ovarian cancer since the study was initiated.
"There are many women who, instead of going straight to surgery when we suspect that they have a pretty advanced cancer (as these patients did), they will start their treatment with chemotherapy and, after a few chemotherapy treatments, will undergo surgery," he said. "At that point the surgery is often less extensive than if you went straight in to do an operation. And with it being less extensive they should have fewer complications after surgery."
"Women with ovarian cancer in whom complete primary cytoreduction is achieved have the best prognosis and longest survival," said Dr. Eisenhauer of Massachusetts General Hospital in Boston and Dr. Chi of Memorial Sloan Kettering Cancer Center in New York. "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."
"Now the data is more solid that there is no evidence of benefit in removing lymph nodes that do not appear to be abnormally enlarged at a time of surgery when women have obviously metastatic ovary or fallopian tube cancer," said Dr. Waggoner.
Dr. Harter did not respond to requests for a telephone interview.
N Engl J Med 2019.