Carcinoembryonic antigen levels and survival in stage III colon cancer: Post hoc analysis of the MOSAIC and PETACC-8 trials

Edouard Auclin, Julien Taieb, Come Lepage, Thomas Aparicio, Roger Faroux, Enrico Mini, Gunnar Folprecht, Ramon Salazar, Magdalena Benetkiewicz, Maria Banzi, Christophe Louvet, Jean Luc Van Laethem, Josep Tabernero, Tamas Hickish, Aimery De Gramont, Thierry Andre, Dewi Vernerey

Research output: Contribution to journalArticle

Abstract

Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level 5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level 5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n ¼ 630), 1.30–5 ng/mL (n ¼ 613), and >5 ng/mL (n ¼ 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of 5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.

Original languageEnglish
Pages (from-to)1153-1161
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number7
DOIs
Publication statusPublished - Jan 1 2019

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Carcinoembryonic Antigen
Colonic Neoplasms
Survival
Disease-Free Survival
Proportional Hazards Models
Survival Rate
Clinical Trials

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Carcinoembryonic antigen levels and survival in stage III colon cancer : Post hoc analysis of the MOSAIC and PETACC-8 trials. / Auclin, Edouard; Taieb, Julien; Lepage, Come; Aparicio, Thomas; Faroux, Roger; Mini, Enrico; Folprecht, Gunnar; Salazar, Ramon; Benetkiewicz, Magdalena; Banzi, Maria; Louvet, Christophe; Van Laethem, Jean Luc; Tabernero, Josep; Hickish, Tamas; De Gramont, Aimery; Andre, Thierry; Vernerey, Dewi.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 28, No. 7, 01.01.2019, p. 1153-1161.

Research output: Contribution to journalArticle

Auclin, E, Taieb, J, Lepage, C, Aparicio, T, Faroux, R, Mini, E, Folprecht, G, Salazar, R, Benetkiewicz, M, Banzi, M, Louvet, C, Van Laethem, JL, Tabernero, J, Hickish, T, De Gramont, A, Andre, T & Vernerey, D 2019, 'Carcinoembryonic antigen levels and survival in stage III colon cancer: Post hoc analysis of the MOSAIC and PETACC-8 trials', Cancer Epidemiology Biomarkers and Prevention, vol. 28, no. 7, pp. 1153-1161. https://doi.org/10.1158/1055-9965.EPI-18-0867
Auclin, Edouard ; Taieb, Julien ; Lepage, Come ; Aparicio, Thomas ; Faroux, Roger ; Mini, Enrico ; Folprecht, Gunnar ; Salazar, Ramon ; Benetkiewicz, Magdalena ; Banzi, Maria ; Louvet, Christophe ; Van Laethem, Jean Luc ; Tabernero, Josep ; Hickish, Tamas ; De Gramont, Aimery ; Andre, Thierry ; Vernerey, Dewi. / Carcinoembryonic antigen levels and survival in stage III colon cancer : Post hoc analysis of the MOSAIC and PETACC-8 trials. In: Cancer Epidemiology Biomarkers and Prevention. 2019 ; Vol. 28, No. 7. pp. 1153-1161.
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title = "Carcinoembryonic antigen levels and survival in stage III colon cancer: Post hoc analysis of the MOSAIC and PETACC-8 trials",
abstract = "Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level 5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96{\%}) and 2,477 (97{\%}) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level 5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75{\%}, 65{\%}, and 45{\%} in a group of patients with CEA level of 0–1.30 ng/mL (n ¼ 630), 1.30–5 ng/mL (n ¼ 613), and >5 ng/mL (n ¼ 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of 5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.",
author = "Edouard Auclin and Julien Taieb and Come Lepage and Thomas Aparicio and Roger Faroux and Enrico Mini and Gunnar Folprecht and Ramon Salazar and Magdalena Benetkiewicz and Maria Banzi and Christophe Louvet and {Van Laethem}, {Jean Luc} and Josep Tabernero and Tamas Hickish and {De Gramont}, Aimery and Thierry Andre and Dewi Vernerey",
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T1 - Carcinoembryonic antigen levels and survival in stage III colon cancer

T2 - Post hoc analysis of the MOSAIC and PETACC-8 trials

AU - Auclin, Edouard

AU - Taieb, Julien

AU - Lepage, Come

AU - Aparicio, Thomas

AU - Faroux, Roger

AU - Mini, Enrico

AU - Folprecht, Gunnar

AU - Salazar, Ramon

AU - Benetkiewicz, Magdalena

AU - Banzi, Maria

AU - Louvet, Christophe

AU - Van Laethem, Jean Luc

AU - Tabernero, Josep

AU - Hickish, Tamas

AU - De Gramont, Aimery

AU - Andre, Thierry

AU - Vernerey, Dewi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level 5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level 5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n ¼ 630), 1.30–5 ng/mL (n ¼ 613), and >5 ng/mL (n ¼ 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of 5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.

AB - Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level 5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level 5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n ¼ 630), 1.30–5 ng/mL (n ¼ 613), and >5 ng/mL (n ¼ 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of 5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.

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