open access publication

Article, 2024

The prognostic value of tumor budding in a thoroughly characterized stage II colon cancer population in the context of a national screening program

Human Pathology, ISSN 0046-8177, 1532-8392, Volume 146, Pages 15-22, 10.1016/j.humpath.2024.02.010

Contributors

Pihlmann Kristensen, Maria (Corresponding author) [1] [2] Korsgaard, Ulrik 0000-0002-1730-388X [1] [2] Timm, Signe 0000-0002-5862-7784 [1] [2] Hansen, Torben Frøstrup 0000-0001-7476-671X [1] [2] Zlobec, Inti 0000-0001-6741-3000 [3] Hager, Henrik 0000-0002-3164-9190 [1] [2] [4] Kjær-Frifeldt, Sanne [1] [2]

Affiliations

  1. [1] University of Southern Denmark
    2. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Vejle Sygehus
    3. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  3. [3] University of Bern
    4. [NORA names: Switzerland; Europe, Non-EU; OECD];
  4. [4] Aarhus University Hospital
    5. [NORA names: Central Denmark Region; Hospital; Denmark; Europe, EU; Nordic; OECD]

Abstract

Tumor budding as a prognostic marker in colorectal cancer has not previously been investigated in a cohort of screened stage II colon cancer patients. We assessed the prognostic significance of tumor budding in a thoroughly characterized stage II colon cancer population comprising surgically resected patients in the Region of Southern Denmark from 2014 to 2016. Tumors were re-staged according to the 8th edition of UICC TNM Classification, undergoing detailed histopathological evaluation and tumor budding assessment following guidelines from the International Tumor Budding Consensus Conference. Prognostic evaluation utilized Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for time to recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). Out of 497 patients, 20% were diagnosed through the national colorectal cancer screening program. High-grade tumor budding (Bd3) was found in 19% of tumors and was associated with glandular subtype, perineural invasion, mismatch repair proficient tumors, and tumor recurrence (p < 0.001, p < 0.001, p = 0.045, and p = 0.007 respectively). In multivariable Cox regression, high-grade budding was a significant prognostic factor for TTR compared to low-grade (Bd3 HR 2.617; p = 0.007). An association between tumor budding groups and RFS was observed, and the difference was significant in univariable analysis for high-grade compared to low-grade tumor budding (Bd3 HR 1.461; p = 0.041). No significant differences were observed between tumor budding groups and OS. High-grade tumor budding is a predictor of recurrence in a screened population of patients with stage II colon cancer and should be considered a high-risk factor in a shared decision-making process when stratifying patients to adjuvant chemotherapy.

Keywords

BD3, BUD group, Cox, Cox proportional hazards models, Cox regression, Denmark, II colon cancer, International, International Tumor Budding Consensus Conference, Kaplan-Meier curves, Region of Southern Denmark, Southern Denmark, TNM classification, TTR, UICC, UICC TNM classification, adjuvant chemotherapy, analysis, assessment, association, buds, cancer, cancer population, cancer screening program, chemotherapy, classification, cohort, colon cancer, colon cancer population, colorectal cancer, colorectal cancer screening program, conference, consensus conference, context, curves, decision-making process, differences, evaluation, factors, glandular subtype, group, guidelines, hazards model, high-grade, high-grade budding, high-grade tumor budding, high-risk factors, histopathological evaluation, invasion, log-rank test, low-grade, low-grade tumor budding, markers, mismatch, mismatch repair-proficient tumors, model, multivariate Cox regression, national colorectal cancer screening program, national screening program, no significant difference, overall survival, patients, perineural invasion, population, population of patients, predictors, predictors of recurrence, process, proficient tumors, prognostic evaluation, prognostic factors, prognostic marker, prognostic significance, prognostic significance of tumor budding, prognostic value, prognostic value of tumor budding, program, proportional hazards model, re-staging, recurrence, recurrence-free survival, region, regression, resected patients, screening population, screening population of patients, screening program, significance of tumor budding, significant difference, stage, stage II colon cancer, subtypes, surgically, surgically resected patients, survival, test, tumor, tumor budding, tumor budding assessment, tumor recurrence, univariate analysis

Funders

  • A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond

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