Prognostic value of ctDNA in stage III colon cancer

Circulating tumour (ct)DNA was found to be the most significant prognostic factor for disease recurrence and death in stage III colon cancer patients eligible for adjuvant therapy in multivariable analyses across 2 trials. ctDNA's prognostic value was independent of disease stage and treatment duration. Immunoscore® was not prognostic in ctDNA-positive patients but remains discriminant in ctDNA-negative patients.

Prof. Julien Taieb (Paris Descartes University, France) presented a combined analysis of 2 trials, IDEA-France (GERCOR; NCT00958737) and IDEA-Greece (HORG; NCT01308086), to investigate ctDNA and assess its prognostic value in terms of time to recurrence (TTR) and overall survival (OS) in patients with stage III colon cancer [1–3]. The rationale is to enhance personalised treatment approaches by leveraging ctDNA to track minimal residual disease, which could significantly improve prognostication. Both Immunoscore® (image analysis of CD3+ and CD8+ cells in the tumour centre and invasion margin) and ctDNA detection (using a clinically validated 16-plex PCR next-generation sequencing assay) were assessed.

Out of 554 participants with available ctDNA results, 445 were ctDNA-negative (80.3%) and 109 were ctDNA-positive (19.7%). Baseline characteristics revealed more T4/N2 cases among ctDNA-positive participants (58% vs 38%; P<0.01). With a median follow-up of over 80 months, ctDNA emerged as an independent prognostic marker for both TTR (adjusted HR 5.75; 95% CI 4.2–7.9; P<0.0001; see Figure) and OS (adjusted HR 5.31; 95% CI 3.8–7.5; P<0.0001). ctDNA's prognostic significance remained robust across various disease stages, treatment durations, and Immunoscore® categories. Immunoscore® showed prognostic value in ctDNA-negative participants but not in ctDNA-positive ones. For ctDNA-negative participants, those with a high Immunoscore® had a 5-year TTR of 92%, compared with 78–82% for those with low/intermediate Immunoscores.

Figure: ctDNA status predicts time to recurrence of stage III colon cancer [1]



In conclusion, this combined analysis of 2 adjuvant trials confirms that post-surgery ctDNA, present in 19.7% of the participants, is a major independent prognostic marker in stage III colon cancer. Immunoscore® also served as an independent prognostic tool in ctDNA-negative participants, comprising 80.3% of the cohort. Key findings include that ctDNA, assessed with a tumour-informed commercial test, significantly correlates with TTR and OS, outperforming previous methylation tests.

1. Taieb J, et al. Combined analyses of ctDNA and Immunoscore in stage III colon cancer patients: a post hoc analysis of the IDEA-France and -Greece trials. Abstract 7MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.
2. Souglakos J, et al. Ann Oncol. 2019;30(8):1304-1310.
3. Gallois C, et al. J Clin Oncol. 2023;41(4):803-815.

Copyright ©2024 Medicom Medical Publishers



Posted on 21 August 202421 August 2024