The prognostic influence of tumour budding in Western patients with stage II colorectal cancer.

Augusto Leite Canguçu,Rachel Riechelmann,Tiago Cordeiro Felismino,Celso Abdon Lopes De Mello,Tatiane Neotti,Roberto Bonfim Pimenta Peixoto,Ediel Valério,Vinicius Fernando Calsavara,Mariana Petaccia De Macedo,Samuel Aguiar Júnior

doi:10.3332/ecancer.2020.1130

Abstract

Background:Tumour budding (TB) refers to loss of tumour cohesiveness and is defined as isolated cells or a cell cluster of up to four tumour cells at the microscopic analysis. The International Tumour Budding Consensus Conference (ITBCC) in 2016 proposed a scoring system to standardise the pathology evaluation of TB in colorectal cancer (CRC) as high (H), intermediate (I) and low (L) TB.Objective:To evaluate the recurrence-free survival (RFS) of stage II CRC patients as per the ITBCC 2016 classification and associations between TB and clinical pathological features.Methods:Cases of stage II CRC undergoing surgery with available tumour tissue underwent central pathology review for TB. Prognostic factors, retrospectively retrieved from electronic medical charts, were evaluated in univariate and multivariate Cox regression analyses for RFS (primary end point).Results:Among 137 patients included, L-TB was observed in 107 (78.1%), I-TB in 21 (15.3%) and H-TB in 9 (6.6%). In a median follow-up of 69 months, the median RFS was 134 months, with 14 patients (10.2%) presenting with tumour recurrence: 10 (9.3%) with L-TB, 2 (9.5%) with I-TB and 2 (22.2%) with H-TB. Perineural invasion was more commonly seen in the H-TB group. In multivariate analysis, TB (H and I versus L; HR = 2.6; p = 0.059) and not receiving adjuvant chemotherapy (HR 3.7; p = 0.020) were independently associated with RFS. Adjuvant chemotherapy was associated longer RFS (HR = 3.7; p = 0.022).Conclusion:In this series of Western patients, TB grade was associated with perineural invasion and increased risk of disease relapse.

Highlights

The main treatment for patients with stage II colorectal cancer (CRC) is surgery with adjuvant chemotherapy, which is still debatable in this setting
In this series of Western patients, Tumour budding (TB) grade was associated with perineural invasion and increased risk of disease relapse
The American Society of Clinical Oncology guidelines published in 2019 added tumour budding (TB) as a prognostic factor for pathological stage II CRC [4], but does not formally recommend to consider it alone to administer adjuvant chemotherapy

Summary

Introduction

The main treatment for patients with stage II colorectal cancer (CRC) is surgery with adjuvant chemotherapy, which is still debatable in this setting. The widely accepted high-risk characteristics used to recommend adjuvant treatment for microsatellite stable tumours are extramural vascular invasion, grade 3 or poorly differentiated histology, pathological T4 stage, perforation and/or obstructive tumours, and less than 12 lymph nodes harvested [4,5,6]. The American Society of Clinical Oncology guidelines published in 2019 added tumour budding (TB) as a prognostic factor for pathological stage II CRC [4], but does not formally recommend to consider it alone to administer adjuvant chemotherapy. In the early 1990s, investigators showed associations between TB and poor tumour cell differentiation, positive lymphatic invasion, greater staging and distant metastasis among Japanese patients with CRC [14,15,16]. The International Tumour Budding Consensus Conference (ITBCC) in 2016 proposed a scoring system to standardise the pathology evaluation of TB in colorectal cancer (CRC) as high (H), intermediate (I) and low (L) TB

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Conclusion