Adding retroperitoneal lymphadenectomy to cytoreductive surgery during primary debulking surgery or interval cytoreductive surgery after neoadjuvant chemotherapy failed to improve progression-free or overall survival in patients with advanced ovarian cancer who have no suspicious nodes, according to the results of the phase III CARACO trial presented at the 2024 ASCO Annual Meeting.1 Moreover, patients who underwent retroperitoneal lymphadenectomy experienced increased morbidity. With a lack of survival benefit and an increased risk of complications, the CARACO study supports de-escalation of therapy with less aggressive surgery for advanced ovarian cancer, omitting retroperitoneal lymphadenectomy in patients with advanced ovarian cancer who have no suspicious nodes.
“The CARACO trial is the only prospectively randomized trial that asks the question of the impact of systematic lymphadenectomy in the setting of neoadjuvant therapy,” said Jean-Marc Classe, MD, PhD, Head of the Oncological Surgery Department at the Institut de Cancérologie de l’Ouest, Nantes University, France.
Jean-Marc Classe, MD, PhD
“Avoiding abdominal retroperitoneal lymphadenectomy with no negative impact on survival reduces the duration of surgery, reduces the duration of hospital stay, and reduces pain and the risk of postoperative complications such as abdominal seroma and bleeding,” Dr. Classe continued. “However, abdominal retroperitoneal lymphadenectomy must be performed in cases of bulky suspicious lymph nodes. CARACO shows that patients with no suspicious lymph nodes should not have abdominal retroperitoneal lymphadenectomy.”
Study Details
The multicenter, phase III CARACO trial focused on 379 patients with FIGO (International Federation of Gynecology and Obstetrics) stage III to IVA epithelial ovarian cancer and no suspicious retroperitoneal lymph nodes who had surgery with primary surgery or interval cytoreductive surgery after neoadjuvant chemotherapy (residual disease < 1 cm). Patients were randomly assigned 1:1 to have surgery with or without retroperitoneal lymphadenectomy. The data cutoff was January 2023. Of note, 22 events were missing from the final analysis.
At baseline, median patient age was approximately 65. About 86% had serous or endometrioid carcinoma, and about 86% had no residual disease. In the arm that had no radical lymphadenectomy vs the arm that had radical lymphadenectomy, surgery was performed with no residual tumor in 85.6% vs 88.3%; the median duration of surgery was 240 minutes vs 300 minutes; 26% vs 21% had primary surgery; and 74% vs 79% had interval surgery.
Among patients who underwent retroperitoneal lymphadenectomy, the median number of resected lymph nodes was 28, including 12 para-aortic lymph nodes and 13 pelvic lymph nodes. A total of 43% of patients had one or more involved lymph nodes.
Key Results
The median progression-free survival for patients who did not undergo retroperitoneal lymphadenectomy was 14.8 months vs 18.5 months for those who did—a difference that was not statistically significant (hazard ratio [HR] =0.96; 95% confidence interval [CI] = 0.77–1.20; P = .712). The median overall survival was 48.9 months for those who omitted retroperitoneal lymphadenectomy vs 58.0 months for those who underwent the more extensive surgery—again a nonsignificant difference (HR = 0.92; 95% CI = 0.72–1.17; P = .489).
“There was more morbidity and mortality in the group that underwent retroperitoneal lymphadenectomy,” Dr. Classe stated.
Within 30 days of surgery, 29.7% of patients in the arm that did not have retroperitoneal lymphadenectomy had a transfusion or blood loss compared with 39.3% of patients who had retroperitoneal lymphadenectomy. Reintervention was needed in 3.1% vs 8.3% of patients, respectively, and urinary injury was reported in 0.0% vs 3.8%, respectively. The 30-day mortality rate was 0.5% and 1.1%, respectively.
Study Limitations and Next Steps
The study had some limitations, Dr. Classe acknowledged. There were fewer events than expected, and when 22 missing events were added to the worst-performing group, there was still no difference in progression-free survival. Also, the study did not include information on mutational status. Although two different populations were included—primary surgery or interval surgery—“this mimics the real life of surgical patients and showed no difference in outcomes,” he said.
The next step will be to determine whether abdominal retroperitoneal lymphadenectomy can be safely omitted in patients with suspicious nodes.
Expert Point of View
Shitanshu Uppal, MD
Discussant of this trial in ovarian cancer, Shitanshu Uppal, MD, of the University of Michigan, stated: “The CARACO trial shows that retroperitoneal lymphadenectomy is futile and carries a high rate of morbidity.”
Dr. Uppal continued: “Congratulations on including a surgical trial in this session. This research is trying to solve whether routine lymph node dissection is needed in advanced high-grade serous ovarian cancer. This is a very important study, because it is the only trial to investigate this question in the neoadjuvant chemotherapy setting. The results are consistent with prior data in ovarian and other cancers.”
In addition, Dr. Uppal noted that the higher rate of complications with abdominal retroperitoneal lymphadenectomy “makes it imperative that quality improvement programs focus on disseminating these data and make it a priority.”
Additional Comments
ASCO expert Michael Lowe, MD, MA, of Emory University Winship Cancer Institute, Atlanta, agreed that the findings of the CARACO study are consistent with studies in breast cancer and melanoma where patients did not undergo removal of clinically normal lymph nodes. “The focus of research should be on more effective therapies,” he said.
Michael Lowe, MD, MA
Julie R. Gralow, MD, FACP, FASCO
ASCO Chief Medical Officer Julie R. Gralow, MD, FACP, FASCO, shared these thoughts: “Based on this study, optimizing surgery for advanced ovarian cancer will include omission of lymphadenectomy. Neither group did very well in this study, and systemic therapy will have the most impact.”
DISCLOSURE: Dr. Classe has served as a consultant or advisor to GlaxoSmithKline, Myriad Genetics, and Roche; and has received reimbursement for travel, accommodations, and expenses from MSD Oncology. Dr. Uppal and Dr. Gralow reported no conflicts of interest. Dr. Lowe has served as a consultant or advisor to Bristol Myers Squibb/Pfizer and Merck; and has received institutional research funding from Bristol Myers Squibb, Castle Biosciences, Delcath Systems, and Regeneron.
REFERENCE
1. Classe JM, Campion L, Lecuru F, 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. 2024 ASCO Annual Meeting. Abstract LBA5505. Presented June 1, 2024.
