Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer

Cosimo Rasola; Pierre Laurent-Puig; Thierry André; Antoine Falcoz; Come Lepage; Thomas Aparicio; Olivier Bouché; Astrid Lievre; Laurent Mineur; Jaafar Bennouna; Christophe Louvet; Jean Baptiste Bachet; Christophe Borg; Dewi Vernerey; Sara Lonardi; Julien Taieb

doi:10.1016/j.ejca.2023.113321

Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer

Eur J Cancer. 2023 Nov:194:113321. doi: 10.1016/j.ejca.2023.113321. Epub 2023 Sep 9.

Authors

Cosimo Rasola¹, Pierre Laurent-Puig², Thierry André³, Antoine Falcoz⁴, Come Lepage⁵, Thomas Aparicio⁶, Olivier Bouché⁷, Astrid Lievre⁸, Laurent Mineur⁹, Jaafar Bennouna¹⁰, Christophe Louvet¹¹, Jean Baptiste Bachet¹², Christophe Borg¹³, Dewi Vernerey⁴, Sara Lonardi¹⁴, Julien Taieb¹⁵

Affiliations

¹ Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, SIRIC CARPEM, Université Paris-Cité, Paris, France; Department of Oncology, Veneto Institute of Oncology IRCCS, Padua, Italy; Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
² Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, AP-HP,Centre Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
³ Sorbonne Université and Medical Oncology Department, Hôpital Saint-Antoine, Paris, France.
⁴ University Hospital of Besançon, Methodology and Quality of Life Unit in Oncology, Besançon, France; INSERM, Établissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.
⁵ Gastroenterology and Digestive Oncology, Hôpital Universitaire Le Bocage, Dijon, France.
⁶ Université Paris-Cité, Gastroenterology Department, Hôpital Saint Louis, APHP, Paris, France.
⁷ Dept of Digestive Oncology, CHU Reims, Reims, France.
⁸ Digestive Unit, Hôpital Universitaire de Pontchaillou, Rennes, France.
⁹ Oncology Department, Clinique Sainte-Catherine, Avignon, France.
¹⁰ Department of Medical Oncology, Hôpital Foch, Suresnes, France.
¹¹ Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France.
¹² Sorbonne University, Hepatogastroenterology and Digestive Oncology Department, Pitié Salpêtrière hospital, APHP, Paris, France.
¹³ Department of Medical Oncology, University Hospital of Besançon, France.
¹⁴ Department of Oncology, Veneto Institute of Oncology IRCCS, Padua, Italy; Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
¹⁵ Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, SIRIC CARPEM, Université Paris-Cité, Paris, France. Electronic address: jtaieb75@gmail.com.

PMID: 37797388
DOI: 10.1016/j.ejca.2023.113321

Abstract

Background: It is intuitively thought that early relapse is associated with poor survival after recurrence (SAR) in resected colon cancer (CC) patients, but this has never been formally studied.

Methods: We pooled data from stage III patients treated with oxaliplatin-based adjuvant therapy in two phase III trials, to analyse time to recurrence (TTR) and its relationship with SAR. TTR and SAR were also studied according to molecular status (mismatch repair (MMR), RAS, and BRAF^V600E). Early relapsing patients were defined as patients having a TTR event within 12 months after starting adjuvant chemotherapy.

Results: 4548 stage III CC patients were included in the present analysis. Deficient MMR (dMMR) CC patients experienced fewer recurrences than proficient (p)MMR CC patients (18.8% versus 27.6%) but had a significantly shorter median TTR (mTTR; 0.74 versus 1.40 years, p < 0.0001). In pMMR patients, BRAF and RAS mutations were also associated with earlier mTTR as compared to double wild-type (WT) patients (0.99 versus 1.38 versus 1.54 years, respectively, p < 0.0001). Early recurrence occurred in 397 patients and was associated with a median SAR (2.2 versus 3.3 years, p = 0.0007). However, this association was mainly due to pMMR/RAS and BRAF^V600E mutated tumours and was not confirmed in dMMR and pMMR/double WT subgroups.

Conclusion: In resected stage III CC treated with standard oxaliplatin-based adjuvant therapy, TTR varies between dMMR, pMMR/RAS, or BRAF^V600E mutated and pMMR/double WT tumours. In addition, early relapse is associated with poor survival, mainly due to patients resected for a pMMR/RAS or BRAF^V600E mutated tumour.

Keywords: Adjuvant; BRAF(V600E) mutation; MSI/dMMR; RAS mutation; Stage III colon cancer; Survival after relapse; Time to recurrence.

MeSH terms

Adenocarcinoma* / pathology
Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / genetics
Colonic Neoplasms* / surgery
DNA Mismatch Repair
Humans
Mutation
Neoplasm Staging
Oxaliplatin / therapeutic use
Prognosis
Proto-Oncogene Proteins B-raf / genetics
Recurrence

Substances

Proto-Oncogene Proteins B-raf
Oxaliplatin

Supplementary concepts

Turcot syndrome