Classification of metastases to MAC, MIC and ITC is of no clinical value in cervical cancer.

DFS did not differ between patients with MAC or MIC and was shorter than in N0.

DFS was significantly shorter in patients with metastases ≥0.4 mm compared to N0.

No subcohort with better prognosis than the rest of the N1 cohort was identified.

LN metastases have a significant negative impact on DFS regardless of the size.

In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis.

We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01–1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges.

LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group.

In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication.

Cervical cancer

Low volume metastasis

Disease-free survival

Histopathological ultrastaging

Isolated tumor cells

Sentinel lymph node

Macrometastasis

Micrometastasis

Classification

Prognosis

© 2022 Published by Elsevier Inc.