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. 2022 May 12;14(10):2389.
doi: 10.3390/cancers14102389.

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry

Lynn E Nooijen  1   2 , Jesus M Banales  3   4   5   6 , Marieke T de Boer  7 , Chiara Braconi  8 , Trine Folseraas  9 , Alejandro Forner  10 , Waclaw Holowko  11 , Frederik J H Hoogwater  7 , Heinz-Josef Klümpen  2   12 , Bas Groot Koerkamp  13 , Angela Lamarca  14 , Adelaida La Casta  15 , Flora López-López  16 , Laura Izquierdo-Sánchez  3 , Alexander Scheiter  17 , Kirsten Utpatel  17 , Rutger-Jan Swijnenburg  2   18 , Geert Kazemier  1   2 , Joris I Erdmann  2   18 ; ENSCCA Group
Affiliations

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry

Lynn E Nooijen et al. Cancers (Basel). .

Abstract

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.

Keywords: lymph nodes; overall survival; perihilar cholangiocarcinoma; recurrence-free survival; resection margin.

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Conflict of interest statement

Angela Lamarca received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, and Delcath; speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA, QED, Servier, Astra Zeneca and EISAI; advisory and consultancy honoraria from EISAI, Nutricia Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, and AstraZeneca; and she is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Alejandro Forner received lecture fees from Bayer, Boston Science, Gilead, and MSD; and consultancy fees from Bayer, AstraZeneca, Roche, SIRTEX, AB Exact Science and Guerbert. Braconi (or spouse) received honoraria from Incyte and Servier, Roche, Eli-Lilly, Pfizer, and Merck-Serono. Kirsten Utpatel received advisory honoraria and lecture fees from BMS and Roche.

Figures

Figure 1
Figure 1
Flow diagram of included patients.
Figure 2
Figure 2
(a): Kaplan–Meier curve for overall survival and lymph node-negative (N0) and lymph node-positive (N+) patients. Only the first 5 years are displayed. Median OS was 34 months (95% CI 27.9–40.1) for the N0 versus 15 months (95% CI 10.6–19.4) for the N1 patients (p < 0.001). (b): Kaplan–Meier curve for overall survival of resection margin-negative (R0) and resection margin-positive (R1) patients. Only the first 5 years are displayed. Median OS was 31 months (95% CI 23.0–39.0) for R0 versus 21 months (95% CI 14.9–27.2) for R1 patients (p = 0.037). (c): Kaplan–Meier curve for overall survival of N0R0, N0R1, N+R0, and N+R1 patients. Only the first 5 years are displayed. Median OS was 38 months (95% CI 28.0–48.0) for N0R0, 30 months (95% CI 19.8–40.2) for N0R1, 18 months (95% CI 10.7–25.3) for N+R0, and 12 months (95% CI 7.7–16.3) for the N+R1 patients (p < 0.001). N0R0 vs. N+R0: p = 0.064, N0R1 vs. N+R1: p < 0.001, N+R0 vs. N+R1: p = 0.061, N0R0 vs. N0R1: p = 0.61.
Figure 3
Figure 3
Estimated cumulative recurrence probability of N0R0, N0R1, N+R0, and N+R1 patients. Only the first 5 years are displayed. The median recurrence-free survival was 27 months (95% CI 20.4–33.6) for N0R0, 33 months (95% CI 19.5–46.5) for N0R1, 14 months (95% CI 7.4–20.6) for N+R0, and 11 months (95% CI 5.7–16.3) for the N+R1 patients (p < 0.001). N0R0 vs. N+R0: p = 0.151, N0R1 vs. N+R1: p < 0.001, N+R0 vs. N+R1: p = 0.109, N0R0 vs. N0R1: p = 0.331.
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