According to results of the large randomized LION Gynecologic Cancer Intergroup trial, routine pelvic and para-aortic lymphadenectomy offers no benefit to patients with advanced ovarian cancer who underwent macroscopic complete resection and had clinically and radiologic negative lymph nodes compared with observation (Abstract 5500). Not only did lymphadenectomy yield no improvement in overall survival (OS), but patients who underwent the procedure faced greater morbidity in terms of serious postoperative complications and greater early mortality following surgery.
“Patients with complete resection during upfront surgery and treated in quality-assured centers have an excellent prognosis. Our data indicate that systematic lymphadenectomy of clinically negative lymph nodes in patients with advanced ovarian cancer and complete resection should be omitted,” concluded Philipp Harter, MD, PhD, of the German Gynecological Oncology Group (AGO) and Kliniken Essen Mitte in Germany, who presented the LION resultsLymph node dissection in patients with advanced ovarian neoplasms varies substantially worldwide, largely because of a lack of clear level I evidence supporting improved survival with this approach. To clearly define the potential benefits of lymphadenectomy in patients with advanced ovarian cancer, the AGO devised the long-term LION trial focused on OS as the primary outcome. Notably, all centers had to demonstrate adequate surgical skills before being allowed to participate in the study.
From December 2008 to January 2012, 650 women with newly diagnosed FIGO stage IIB-IV advanced ovarian cancer who had undergone macroscopic complete resection and had clinically and radiographic negative lymph nodes underwent random assignment to pelvic and para-aortic lymphadenectomy or no lymphadenectomy. Patients were well balanced at baseline with respect to demographics and disease characteristics, and similar proportions in the lymphadenectomy and no-lymphadenectomy arms went on to receive platinum/taxane-based chemotherapy following surgery (79.6% vs. 84.6%, respectively).
Of the 323 women who underwent lymphadenectomy, a median of 57 lymph nodes were removed (35 pelvic, 22 para-aortic). Of note, 56% of patients had micrometastases in the removed lymph nodes.
Lymphadenectomy offered no efficacy advantages over the lymph node–sparing approach. Median OS reached 65.5 months in the lymphadenectomy arm compared with 69.2 months in the no-lymphadenectomy arm (HR 1.057, 95% CI [0.833, 1.341]; p = 0.65). Moreover, both arms demonstrated a median progression-free survival of 25.5 months (HR 1.106, 95% CI [0.915, 1.338]).
Quality-of-life outcomes were also identical between arms at baseline, discharge, the end of chemotherapy, and 6 months postchemotherapy.
The two arms differed on perioperative and postoperative outcomes. Lymphadenectomy, compared with no lymphadenectomy, required an additional hour of surgery (mean time: 340 vs. 280 min; p < 0.001), resulted in greater blood loss (median volume: 650 vs. 500 mL; p < 0.001), and more frequently necessitated transfusion (63.7% vs. 56.0%; p = 0.005). Following surgery, lymphadenectomy, compared with no lymphadenectomy, was associated with significantly higher rates of relaparotomy for complications (12.4% vs. 6.5%; p = 0.01), infections (25.8% vs. 18.6%; p = 0.03), and mortality within 60 days of surgery (3.1% vs. 0.9%; p = 0.049).
Given these findings, discussant Ritu Salani, MD, MBA, of The Ohio State University Wexner Medical Center, remarked, “I agree with the authors that omitting systemic lymph node dissection in patients who have both radiographic and clinically negative lymph nodes is acceptable.” She added, “Without doing any analysis, you can expect that this will have cost-effective benefits.”
Dr. Salani did, however, emphasize one major pitfall of the study. “Our fellows are getting less exposure to lymph node dissections,” she said. “We need to continue to challenge ourselves to develop intentional surgical curricula to maintain excellent surgical skills.”