Women with advanced ovarian cancer and clinically negative lymph nodes at surgery did not live longer if they underwent pelvic and paraaortic lymphadenectomy, final results of a randomized trial showed.
Patients who underwent lymphadenectomy had median overall survival of 65.5 months versus 69.2 months without the procedure. Progression-free survival (PFS) also did not differ between the groups. Serious postoperative complications occurred twice as often with lymphadenectomy, and the lymphadenectomy group had a significantly higher 60-day mortality.
Published in the New England Journal of Medicine, the results confirmed a 2017 presentation at the American Society of Clinical Oncology (ASCO) meeting.
“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,” Phillipp Harter, MD, of Kliniken Essen-Mitte in Germany, and coauthors said of their findings.
“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.”
The results were consistent with one prior randomized trial, which had a number of limitations related to design and inclusion criteria, they added.
Authors of an accompanying editorial cited medical dogma for a persistent belief that regional lymph nodes are a “pharmacologic sanctuary” containing a tumor not eliminated by chemotherapy. Multiple retrospective analysis supported that view.
“Women with ovarian cancer in whom complete primary cytoreduction is achieved have the best prognosis and longest survival,” wrote Eric L. Eisenhauer, MD, of Massachusetts General Hospital in Boston, and Dennis S. Chi, MD, of Memorial Sloan Kettering Cancer Center in New York City. “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.”
In the absence of data from a well-designed, randomized trial, the necessity for systematic lymphadenectomy remained an open question. Harter and colleagues sought to accumulate high-quality data by means of “more precise and homogeneous selection of both the trial population … and the procedure … and inclusion of a quality-of-life evaluation … to balance the potential additional treatment burden of this surgical procedure with its potential benefits.”
The Lymphadenectomy in Ovarian Neoplasms (LION) trial involved 647 patients enrolled at multiple centers in Germany. Participating centers qualified for the trial by providing anonymous cases that were evaluated for quality. Eligible patients had FIGO stage IIB through IV advanced ovarian cancer, good performance status, and cancers that surgeons deemed feasible for complete macroscopic resection. The primary endpoint was overall survival.
The results showed no significant difference in overall survival between the two treatment groups, as lymphadenectomy was associated with a hazard ratio of 1.06 (95% CI 0.83-1.34). Both groups had a median PFS of 25.5 months.
Serious postoperative complications occurred in 12.4% of the lymphadenectomy arm and 6.5% of the patients who did not have lymphadenectomy (P=0.01). The 60-day mortality was 3.1% with lymphadenectomy and 0.9% without (P=0.049).
The results made a compelling case for skipping lymphadenectomy in appropriately selected patients, said Ritu Salani, MD, of Ohio State University Comprehensive Cancer Center in Columbus. As the invited discussant for the study’s presentation at ASCO, she called it the most impactful gynecologic oncology data reported at the meeting. Almost 2 years later, she’s heeding the message that came from the trial.
“Since that presentation, I have actually changed my practice pattern, and I think many of my colleagues also have changed their practice patterns,” she told MedPage Today this week. “This study kind of confirmed that omitting lymph nodes in appropriate patients with ovarian cancer not only does not affect oncologic outcomes but also is safer.”
Jason Wright, MD, of New York-Presbyterian/Columbia University Medical Center in New York City, echoed that sentiment, adding that the results suggest that lymphadenectomy “should be avoided if the lymph nodes are not enlarged. This will help guide surgical management of women with ovarian cancer and hopefully reduce complication rates.”
The trial was sponsored by Philipps University Marburg Medical Center in collaboration with the German Research Foundation.
Harter disclosed relationships with AstraZeneca, Roche, Tesaro, Clovis, Pharmamar, Lilly, Medac, Stryker, and Immunogen. One or more coauthors disclosed relationships with AstraZeneca, Roche, Tesaro, Clovis, BioCad, Genmab, Pfizer, MedConcept, Celgene GmbH, Pierre Fabre GmbH, Intuitive Surgical, Medtronic, ProStrakan, Riemser, Teva, Cambridge Medical Robotics, Merck, GlaxoSmithKline, and Sensor Kinesis.
Eisenhauer disclosed relationships with TransEnterix, Covidien, Janssen Biotech, Clovis Oncology, and Tesaro. Chi disclosed relationships with Bovie Medical, Verthermia, CSurgeries, and Intuitive Surgical.