CHICAGO -- Omitting lymphadenectomy in patients with advanced epithelial ovarian cancer treated with primary or interval cytoreductive surgery after neoadjuvant chemotherapy did not compromise outcomes and resulted in less severe morbidity, the phase III randomized CARACO trial showed.
Median progression-free survival was 14.8 months among patients who did not undergo retroperitoneal lymphadenectomy compared with 18.6 months for those who did (HR 0.96, 95% CI 0.77-1.20, P=0.712), reported Jean-Marc Classe, MD, of Nantes Université in France, during the American Society of Clinical Oncology (ASCO) annual meeting.
Likewise, median overall survival (OS) was not significantly different between the two groups -- 48.9 months in the no-lymphadenectomy arm versus 58.8 months in the lymphadenectomy arm (HR 0.92, 95% CI 0.72-1.17, P=0.489).
"CARACO is the only prospectively randomized trial asking the question of the impact of systematic lymphadenectomy at the time of interval surgery after neoadjuvant chemotherapy," Classe noted.
The mainstay of treatment for advanced ovarian cancer is primary surgery with a goal of macroscopically complete resection of all visible tumor, followed by platinum-based chemotherapy. More recent regimens have incorporated systemic therapy with bevacizumab (Avastin) combined with chemotherapy. An abdominal retroperitoneal lymphadenectomy is performed in the case of bulky suspicious lymph nodes.
Although lymphatic spread is an important prognostic factor, the therapeutic role of systematic lymphadenectomy in the treatment of advanced epithelial ovarian cancer is still controversial.
In the case of no suspicious bulky lymph nodes, retroperitoneal lymphadenectomy showed lymph node involvement in almost 50% of CARACO patients, said Classe, "and yet, adding a retroperitoneal lymphadenectomy in these patients during primary surgery does not improve survival," as evidenced by the results from the Lymphadenectomy in Ovarian Neoplasms (LION) trial, which were first presented at the ASCO meeting in 2017.
Invited discussant Shitanshu Uppal, MBBS, of the University of Michigan in Ann Arbor, said that the study showed that "retroperitoneal lymph node dissection of normal-appearing nodes during ovarian debulking is futile," while morbidity of lymph node dissection is high.
The results are consistent with prior data not only in ovarian cancer but other cancers as well, he added.
"As the utilization of neoadjuvant chemotherapy goes up, these results are really helpful in consolidating the results of the prior study, LION, that lymph node dissection has no role in interval complete surgery," he said.
After presentation of the LION results in 2017, the inclusion rate stagnated, leading to the premature closing of the trial, said Classe, and resulted in 22 missing events and a power analysis of only 78%.
A maximal bias analysis in which the missing 22 events were added to the no-lymphadenectomy group to virtually increase the difference between groups did not change the conclusion -- there was still no statistical difference in median PFS between the two arms (P=0.161).
was a multicenter trial that included 379 patients with epithelial ovarian cancer. Inclusion criteria included International Federation of Gynecology and Obstetrics (FIGO) stage III-IVa cancer (pleural effusion); no suspicious retroperitoneal lymph nodes >2 cm on pelvic CT or MRI, and no nodes palpated during surgery; optimal surgery achievable (primary surgery, or if not, feasible interval complete surgery after neoadjuvant chemotherapy); and residual tumor <1 cm.
Patients were randomized 1:1 to surgery with or without systematic lymphadenectomy. All patients received standard-of-care chemotherapy and maintenance therapy after surgery.
Baseline characteristics were similar between the two groups. Median patient age was 64-65, and 86% to 87.6% had serous or endometrioid carcinoma. The surgical strategy was primary surgery in 26% of the patients randomized to no lymphadenectomy and 21% in those randomized to lymphadenectomy. In the lymphadenectomy group, the median number of nodes resected was 28, and 43% had involvement of ≥1 lymph nodes. Bevacizumab maintenance was used in 24% of patients in each arm.
The difference in PFS and OS remained nonsignificant (P=0.208 and P=0.224, respectively) in the subgroup of patients with high-grade serous or endometrioid disease, said Classe. The results were also consistent in the subgroup of patients undergoing interval surgery (P=0.374 for PFS and P=0.280 for OS differences).
Patients who underwent lymphadenectomy compared with those who did not were more likely to need transfusion or had blood loss (39.3% vs 29.7%; P=0.049) and need reintervention (8.3% vs 3.1%; P=0.031), and were more likely to have urinary injury (3.8% vs 0%; P=0.006).
Disclosures
The CARACO study was funded by a national grant from the National Institute of Cancer in France.
Classe reported consulting relationships with GSK, Myriad Genetics, and Roche, and receiving support for travel expenses from MSD Oncology.
Primary Source
American Society of Clinical Oncology
Classe JM, et al "Omission of lymphadenectomy in patients with advanced epithelial ovarian cancer treated with primary or interval cytoreductive surgery after neoadjuvant chemotherapy: the CARACO phase III randomized trial" ASCO 2024; Abstract LBA5505.