Results from the phase 3 CARACO trial found that omitting retroperitoneal pelvic and paraaortic lymphadenectomy (RPPL) during surgery did not improve survival, while RPPL resulted in more frequent serious post-operative complications among patients with newly diagnosed advanced epithelial ovarian cancer.

These data were first presented by Jean-Marc Classe, MD, PhD, Nantes University, Nantes, France, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

While patients in this population, who do not have suspicious bulky lymph nodes, end up having lymph node involvement in almost 50% of cases, the lion trial revealed that adding RPPL during primary surgery does not improve survival. Dr Classe explained, “CARACO trial addresses the question of systemic lymphadenectomy in patients with no suspicious lymph nodes, notably during interval surgery after neoadjuvant chemotherapy.”

In this multi-center, phase 3 trial, 379 patients with newly diagnosed advanced epithelial ovarian cancer and no pre- and intra-operative suspicious lymph nodes were randomized, intra-operatively, to either receive RPPL (n = 181) or not (n = 187). Patients were stratified by surgical strategy (primary surgery or surgery following neoadjuvant chemotherapy). The target sample size of 450 was not reached, as results from the LION trial stopped inclusion. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), safety (morbidity and mortality within 30 days of surgery, and surgical outcome.”

In the “no RPPL” arm, the rate of no residual disease following surgery was 85.6% vs 88.3% in the RPPL arm. In the RPL arm, the rate of lymph node involvement was 43%. After a median follow-up duration of 9 years, the median PFS in the “no RPPL” arm was 14.8 months and 18.5 months in the RPPL arm (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78 to 1.22; P = .86). The median OS was 48.9 months and 58.0 months respectively, which does not represent a statistically significant difference (HR, 0.96; 95% CI, 0.75 to 1.22; P = .72). PFS and OS measures were similar between subgroups of patients with a complete surgery vs surgery following neoadjuvant chemotherapy. The rate of serious post-operative complications was higher in the RPPL arm including re-laparotomies (8.3% in the RPPL arm vs 3.2% in the “no RPPL” arm; P = .03) and transfusion rate (34% vs 25%; P = .05). Mortality within 60 days of surgery was similar between the 2 arms (1.1% vs 0.5%; P = .54).

Dr Classe and coauthors concluded this trial “is the first randomized trial showing that systemic lymphadenectomy should be omitted in [advanced epithelial ovarian cancer] with clinically negative lymph nodes also in patients undergoing neoadjuvant chemotherapy and interval complete surgery.” He added, “This surgical de-escalation allows to significantly reduce serious post-operative morbidity.

Source:

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. Presented at the 2024 ASCO Annual Meeting. March 31-June 4, 2024; Chicago, IL. Abstract #LBA5505