Incidence and impact of low-volume lymph node metastasis in apparent early-stage ovarian cancer: MICR-OVARY study

Objective: Sentinel lymph node (SLN) biopsy is an emerging technique in apparent early-stage ovarian cancer, with the potential to detect low-volume lymph node metastases. However, the prognostic value of low-volume metastases is still unknown. This study aimed to assess the incidence and the prognosis of low-volume metastases detected in patients with apparent early-stage ovarian cancer undergoing SLN biopsy as part of a clinical trial. Methods: Retrospective, multi-center, international study. Inclusion criteria were apparent International Federation of Gynecology and Obstetrics 2014 stage I to II epithelial ovarian cancer, undergoing SLN biopsy with systematic bilateral pelvic and para-aortic lymphadenectomy, and complete peritoneal surgical staging, from October 2012 to December 2023. In the absence of lymph-node macro-metastasis, at least 4-level ultra-staging at the SLN was performed. Fertility-sparing surgery or no SLN detection were exclusion criteria. Low-volume metastases were defined as any tumor deposit ≤2 mm (isolated tumor cells as <0.2mm, micro-metastasis as 0.2-2 mm). Descriptive statistics and survival analyses, including multi-variable Cox regression, were performed. Results: SLN mapping was attempted in 260 patients. At least 1 SLN was detected in 199 (76.5%) patients, and low-volume metastases were found in 14/199 (7.0%), including 7 (3.5%) isolated tumor cells and 7 (3.5%) micro-metastases. Macro-metastases were identified in 18/199 (9.0%) patients. Among patients with lymph node metastases, 29/32 (90.6%) received adjuvant chemotherapy, including 11/14 (78.6%) with low-volume metastases. Median follow-up was 37 months (95% confidence interval [CI] 34.5 to 39.5). Three-year disease-free survival was 89.9% in node-negative patients, 100.0% in patients with low-volume metastasis, and 64.2% in patients with macro-metastasis (p < .001). Three-year overall survival was 98.2%, 100.0%, and 87.8%, respectively (p < .001). Lymph node macro-metastasis was the only factor independently associated with worse disease-free survival (hazard ratio 1.532, 95% CI 1.111 to 2.112, p = .009) and overall survival (hazard ratio 1.894, 95% CI 1.091 to 3.286, p = .001). Conclusions: Lymph node low-volume metastases in apparent early-stage ovarian cancer were present in 7% of patients, and none of these patients experienced recurrence or death. Lymph node macro-metastasis independently impaired disease-free and overall survival.