Roxanne Nelson, BSN, RN

June 13, 2017

CHICAGO — Patients with advanced ovarian cancer who undergo a complete resection need not also undergo systematic lymphadenectomy  because it has no effect on progression-free survival (PFS) or overall survival (OS).

This is the conclusion from a large randomized trial, the Lymphadenectomy In Ovarian Neoplasms (LION) study.

The results showed that the median OS in patients who underwent lymphadenectomy was similar to that in patients who did not (65.5 vs 69.2 months) and that the median PFS was the same  in both groups (25.5 months). But patients who underwent  lymphadenectomy had more complications, including infections and need for transfusions.

The results of the study were presented here at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

In a "Highlights of the Day" discussion, Linda Duska, MD, professor of obstetrics and gynecology at the University of Virginia, Charlottesville, agreed with the investigators that these findings demonstrate that lymphadenectomy can be safely omitted because it did not improve survival outcomes.

There was no effect on survival even though more than half of the patients — 56% — had occult nodal disease, she said.

"This debunks the 'sanctuary' node theory, which many of us learned during our training, that it's important to remove these sanctuary nodes," Dr Duska said.

All patients underwent very aggressive surgeries, with more than 50% having diaphragm stripping as part of the procedure, she noted. "Over half had a GI [gastrointestinal] resection, and about 20% had a splenectomy in each arm," she said. "The number of lymph nodes resected was very high, with a median of 57."

So are the results of this trial practice changing?

"Yes, it is practice changing," said Dr Duska, but she cautioned that "it needs to be in this particular group of patients, who can be completely cytoreduced and who have no bulky lymph nodes."

No Survival Effect, Increased Complications

The LION study, led by Philipp Harter, MD, PhD, from the Kliniken Essen-Mitte in Germany, was conducted in 647 patients with newly diagnosed stage IIB-IV ovarian cancer who had undergone macroscopic complete resection and had pre- and intraoperatively negative lymph nodes. They were randomly assigned to lymphadenectomy (n = 323) or control  (n = 324).

"Upfront surgery aiming at macroscopic complete resection is the goal in patients with primary advanced ovarian cancer," said Dr Harter, who presented the findings at the meeting.

While some previous research has suggested a survival advantage to lymphadenectomy, there is no level 1 evidence regarding the role of systematic pelvic and para-aortic lymphadenectomy in this specific population of patients with ovarian cancer. Thus, the surgical management is very heterogeneous worldwide, he commented.

Dr Harter pointed out that to participate in the LION trial, centers had to meet certain qualifications.

"They had to provide 12 anonymous surgical and pathologic reports of patients and systematic pelvic and para-aortic lymphadenectomy of the preceding 12 months," he said. "Surgery was defined as adequate if at least 20 pelvic and 10 para-aortic lymph nodes were removed, and the surgical report described systematic lymphadenectomy covering all predefined anatomical regions."

The primary endpoint of the study was OS.

The use of postoperative platinum/taxane-based chemotherapy was similar in both groups (85% in the control group and 80% in the lymphadenectomy group).

The median OS for the entire cohort was 67.2 months, with a 5-year OS rate of 55.9%; the median PFS was 25.5 months.

The OS did not differ between groups (hazard ratio [HR], 1.057), nor did median PFS (HR, 1.106).

One difference between the groups was the rate of complications, Dr Hartner noted. Surgery in the lymphadenectomy group took about an hour longer (P < .001) and had significantly more blood loss (+150 mL) during surgery (P < .001); these patients also had a greater need for blood transfusions (63.7% vs 56%; P = .005).

The rate of infections requiring treatment with antibiotics was also significantly higher in the lymphadenectomy group (25.8% vs 18.6%; P = .03), as was the 60-day postoperative mortality rate (3.1% vs 0.9%; P = .049).  

More patients undergoing lymphadenectomy required postoperative care in the intensive care unit (77.6% vs 69.4%; P = .01), and the rate of re-laparotomy for complications was also almost double (12.4% vs 6.5%; P = .01).

"Systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancer with both intra-abdominal complete resection and clinically negative lymph nodes neither improves overall or progression-free survival, despite detecting and removing subclinical retroperitoneal lymph node metastases in 56% of patients," Dr Harter concluded. "Our data indicate that systematic lymphadenectomy of clinical negative lymph nodes in patients with advanced ovarian cancer and complete resection should be omitted."

Questions Remain

Dr Duska noted that even though the study did not look at cost, omitting lymphadenectomy would probably be associated with cost savings based on the lower rate of complications and shorter surgical times observed in this study.

But the study does raise two questions, she emphasized, "the first of which is, Do these findings apply to patients who received neoadjuvant chemotherapy? I don't think we know the answer to that."

The other question was how these results might affect  the current staging system.

"About 5% of patients had only stage I disease, so we can assume that if we don't do a full lymphadenectomy, then some women will be understaged," she said. "And based on this trial, I would suggest that these results be applied to those women who have bulky peritoneal disease that can be completely cytoreduced and have no evidence of bulky peritoneal nodes."

Dr Duska has disclosed relationships with Advance Medical, the British Journal of Obstetrics and Gynecology, ClearView Healthcare Partners, Parexel, UpToDate, AbbVie (institutional), Aduro Biotech (institutional), Advaxis (institutional), Aeterna Zentaris (institutional), Bristol-Myers Squibb (institutional), Cerulean Pharma (institutional), GlaxoSmithKline (institutional), Millennium (institutional), Millennium (institutional), Novartis ( institutional), Syndax (institutional), Tesaro (institutional), and Genentech. Dr Harter has disclosed relationships with AstraZeneca, Roche,  AstraZeneca, Clovis Oncology, PharmaMar, Roche, Sotio, Tesaro, and Medac.

American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.  Abstract 5500. Presented June 3, 2017.

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