No Value for Lymphadenectomy in Advanced Ovarian Cancer

Most patients with ovarian cancer are diagnosed in an advanced stage. The standard of care for these patients is maximal cytoreductive surgical debulking, followed by systemic treatment including platinum-based chemotherapy and targeted therapies (eg, bevacizumab, olaparib maintenance in patients harboring BRCA mutations). The goal of primary surgical cytoreduction is removal of as much of the visible tumor as possible. It is known that the size of postoperative residual tumor after maximal cytoreduction is an important prognostic factor. However, pelvic and paraaortic lymph nodes are often sites of microscopic metastases, and the value of systematic lymphadenectomy during primary surgery has been a controversial issue for decades.

In an attempt to evaluate the efficacy of lymphadenectomy as a treatment for advanced ovarian cancer, the prospectively randomized phase III LION trial (N = 647) compared lymphadenectomy with no lymphadenectomy in patients with newly diagnosed advanced ovarian cancer (FIGO stage IIB-IV) who had undergone macroscopically complete surgical resection and had visibly normal lymph nodes. Of note, patients were assigned intraoperatively and only centers with high-quality surgical skills were able to participate in the trial.

Systematic pelvic and paraaortic lymphadenectomy following macroscopically complete resection in patients with normal lymph nodes before and during surgery did not improve overall survival (OS, primary endpoint) or progression-free survival (PFS) compared to no lymphadenectomy. The OS was 69.2 months in the group that did not receive lymphadenectomy, compared to 65.5 months in patients who received lymphadenectomy (HR 1.06, P = .065), and the median progression-free survival was 25.5 months in both treatment groups (HR 1.11, P = .29). There were no significant differences in postoperative systemic therapy between the two treatment groups.

Surgical procedures were prolonged in patients receiving lymphadenectomy and associated with increased blood loss and infections compared to those who did not receive lymphadenectomy. In addition, more serious postoperative complications occurred in patients who underwent lymphadenectomy, including an increased incidence of repeat laparotomy (12.4% vs 6.5%; P = .01) and higher mortality within 60 days after surgery (3.1% vs 0.9%; P = .049). However, there were no clinically meaningful differences in global health status and quality of life between the two groups.

The investigators concluded that results from the LION trial provide level 1 evidence to the long-standing debate about the role of systematic lymphadenectomy. The results confirmed that patients with advanced ovarian cancer and clinically negative lymph nodes who underwent maximal macroscopic cytoreduction do not benefit from lymphadenectomy and this treatment approach is associated with increased incidence of postoperative complications. In an accompanying commentary, the authors agreed, highlighting that debulking surgery to achieve complete primary cytoreduction is a complex surgical procedure associated with a number of risks for patients, and that the addition of lymphadenectomy is an ineffective approach associated with increased risk of complications and prolonged recovery time.  Based on results from this study, lymphadenectomy should not be performed in patients with advanced ovarian cancer and clinically negative lymph nodes after maximal surgical cytoreduction.

N Engl J Med. 2019;380:822-832.

N Engl J Med. 2019;380:871-873.

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