TY - JOUR
T1 - Stratification of lymph node metastases as macrometastases, micrometastases, or isolated tumor cells has no clinical implication in patients with cervical cancer
T2 - Subgroup analysis of the SCCAN project
AU - Dostálek, Lukáš
AU - Benešová, Klára
AU - Klát, Jaroslav
AU - Kim, Sarah H.
AU - Falconer, Henrik
AU - Kostun, Jan
AU - dos Reis, Ricardo
AU - Zapardiel, Ignacio
AU - Landoni, Fabio
AU - Ortiz, David Isla
AU - van Lonkhuijzen, Luc R. C. W.
AU - Lopez, Aldo
AU - Odetto, Diego
AU - Borčinová, Martina
AU - Jarkovsky, Jiri
AU - Salehi, Sahar
AU - Němejcová, Kristýna
AU - Bajsová, Sylva
AU - Park, Kay J.
AU - Javůrková, Veronika
AU - Abu-Rustum, Nadeem R.
AU - Dundr, Pavel
AU - Cibula, David
N1 - Funding Information: This work was supported by grants from Charles University in Prague (COOPERATIO, UNCE 204065 ), Ministry of Health of the Czech Republic ( MH CZ – DRO-VFN64165 ), the Czech Health Research Council ( NV19-03-00023 ), and the National Institutes of Health / National Cancer Institute Cancer Center ( P30 CA008748 ). The funding sources were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Publisher Copyright: © 2022
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Cervical cancer
KW - Classification
KW - Disease-free survival
KW - Histopathological ultrastaging
KW - Isolated tumor cells
KW - Low volume metastasis
KW - Macrometastasis
KW - Micrometastasis
KW - Prognosis
KW - Sentinel lymph node
UR - http://www.scopus.com/inward/record.url?scp=85142735042&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ygyno.2022.11.017
DO - https://doi.org/10.1016/j.ygyno.2022.11.017
M3 - Article
C2 - 36442426
SN - 0090-8258
VL - 168
SP - 151
EP - 156
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -