Tumour budding predicts increased recurrence after curative resection for T2N0 colorectal cancer

Tumour budding predicts increased recurrence after curative resection for T2N0 colorectal cancer

Can J Surg 2019;62(5):334-339 | PDF

Richard Garfinkle, MD; Lawrence Lee, MD, PhD; Marylise Boutros, MD; Marie-Josee Cardin, MD; Alan Spatz, MD; Nancy Morin, MD

Abstract

Background: Tumour budding is defined as the presence of a cluster of fewer than 5 cells along the invasive margin. It may confer a worse prognosis in colorectal cancer, but its importance in pT2N0 colorectal cancer is unknown. This study aimed to determine the prognostic value of tumour budding in pT2N0 colorectal cancer.

Methods: This was a retrospective cohort study with prospective assessment of tumour budding by 2 pathologists. We included all patients who underwent elective curative resection for pT2N0 colorectal cancer except those with hereditary colorectal cancer syndromes, inflammatory bowel disease or positive resection margins, those who received neoadjuvant or adjuvant therapy and those who died within 90 days of operation. Patients were classified as having high-grade tumour budding (≥ 10 budding foci per high-power field) or low-grade tumour budding (< 9 budding foci per high-power field). The main outcome measure was locoregional or distant recurrence.

Results: Of 85 patients, 36 had high-grade tumour budding and 49 had low-grade tumour budding. The overall recurrence rate was 11% (9/85) and median follow-up was 41.0 months (interquartile range 22.0–68.0). Interrater reliability for tumour budding assessment was excellent (κ = 0.86, 95% confidence interval [CI] 0.76–0.96). There were more recurrences in patients with high-grade tumour budding (7/36, 19.4% v. 2/49, 4.1%; p = 0.020). On multivariate analysis, after we adjusted for confounders, the presence of high-grade tumour budding was independently associated with recurrence (hazard ratio 5.11, 95% CI 1.01–25.9).

Conclusion: Tumour budding was independently associated with increased recurrence after pT2N0 colorectal cancer resection. It offers additional prognostic information that may affect treatment strategy.

Résumé

Contexte : Le bourgeonnement tumoral se définit par la présence d’un amas de 5 cellules ou moins le long de la marge invasive. Il pourrait conférer un pronostic plus sombre dans le cancer colorectal, mais on ignore sa portée dans le cancer colorectal de stade pT2N0. Cette étude visait à déterminer la valeur pronostique du bourgeonnement tumoral dans un cancer colorectal de stade pT2N0.

Méthodes : Il s’agit d’une étude de cohorte rétrospective avec évaluation prospective du bourgeonnement tumoral par 2 pathologistes. Nous avons inclus tous les patients ayant subi une résection curative non urgente pour un cancer colorectal de stade pT2N0, sauf ceux qui présentaient un syndrome de cancer colorectal héréditaire, une maladie inflammatoire de l’intestin ou des marges de résection positives ceux qui avaient reçu des traitements néoadjuvants ou adjuvants et ceux qui étaient décédés dans les 90 jours suivant l’intervention. Les patients ont été classés selon qu’ils avaient un bourgeonnement tumoral de haut grade (≥ 10 foyers bourgeonnants par champ à fort grossissement) ou bourgeonnement tumoral de bas grade (< 9 foyers bourgeonnants par champ à fort grossissement). Le principal paramètre était la récurrence locorégionale ou distante.

Résultats : Sur 85 patients, 36 présentaient un bourgeonnement tumoral de haut grade, et 49, de bas grade. Le taux de récurrence global a été de 11 % (9/85) et le suivi médian a été de 41,0 mois (intervalle interquartile 22,0–68,0). La fiabilité interévaluateur de l’évaluation du bourgeonnement tumoral a été excellente (κ = 0,86, intervalle de confiance [IC] de 95 % 0,76–0,96). Les récurrences ont été plus nombreuses chez les patients qui avaient un bourgeonnement tumoral de haut grade (7/36, 19,4 % c. 2/49, 4,1 %; p = 0,020). À l’analyse multivariée, après ajustement pour tenir compte des variables de confusion, la présence de bourgeonnement tumoral de haut grade s’est révélée indépendamment liée à la récurrence (risque relatif 5,11, IC de 95 % 1,01–25,9).

Conclusion : Le bourgeonnement tumoral s’est révélé indépendamment lié à l’augmentation des récurrences après la résection pour cancer colorectal de stade pT2N0. Il offre une information pronostique additionnelle qui pourrait influer sur la stratégie thérapeutique.


Presented at the American Society of Colon and Rectal Surgeons 2013 Annual Scientific Meeting, Apr. 27 – May 1, 2013, Phoenix, Ariz.

Accepted Jan. 3, 2019

Acknowledgements: The authors thank Elektra McDermott for her editorial assistance and preparation of the manuscript.

Affiliations: From the Division of Colon and Rectal Surgery (Garfinkle, Lee, Boutros, Morin) and the Department of Pathology (Spatz, Cardin), Sir Mortimer B. Davis Jewish General Hospital, Montreal, Que.

Competing interests: None declared.

Funding: R. Garfinkle was supported by a Canadian Institutes of Health Research Summer Research Bursary from the McGill University Faculty of Medicine. L. Lee was supported by the Quebec Health Science Research Fund (FRQ-S). The funders had no role in the conduct of this study.

Contributors: All authors designed the study and acquired and analyzed the data. R. Garfinkle wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper. All authors agreed to be accountable for all aspects of the work.

DOI: 10.1503/cjs.019017

Correspondence to: N. Morin, 3755 Cote-Sainte-Catherine Road, G-304, Montreal QC H3T 1E2, nancy.morin@mcgill.ca