Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II-III colon cancer

Abstract

In cancer patients, only a small fraction of circulating cell-free DNA (cfDNA) consists of circulating tumor DNA (ctDNA), which contains tumor-specific features. Detecting ctDNA in peripheral blood through liquid biopsy offers a safe, noninvasive alternative to traditional tissue biopsy, with the added benefit of enabling repeated testing over time. This study investigates the potential of liquid biopsy as an innovative and noninvasive prognostic tool for patients with stage II-III colon cancer. Specifically, we analyzed the presence of cfDNA harboring tumor-specific mutations, previously identified in tumor tissue via next-generation sequencing (NGS), both before and after therapeutic surgery. Our aim was to assess its predictive value for relapse, ultimately guiding therapeutic decisions and improving patient outcomes. Our results demonstrate that the presence of ctDNA before surgery was significantly associated with disease relapse, indicating its potential as a predictive biomarker. In this cohort, ctDNA detection after surgery, during adjuvant chemotherapy, did not maintain the same predictive value. This suggests that preoperative ctDNA analysis may provide critical prognostic information, while post-surgical ctDNA monitoring, in this specific setting, may be influenced by treatment dynamics. In conclusion, we found that combining NGS profiling of the primary tumor tissue with droplet digital PCR (ddPCR)-based analysis of cfDNA provides a comprehensive approach to therapy monitoring in stage II-III colon cancer patients. Liquid biopsy offers valuable insights into treatment response and disease progression while serving as a noninvasive and repeatable method for routine clinical care.

Keywords: Colorectal cancer; Droplet digital PCR; Liquid biopsy; Tumoral cell-free DNA.

Fig. 1

A Summary of trunk/driver mutations identified in patients’ tumor tissues. B Disease-free survival (DFS) of patients stratified according to the presence of cfDNA harboring the same variants identified in tumor tissue, detected in pre-surgical blood samples. C DFS of patients stratified based on the presence of cfDNA harboring the same variants identified in tumor tissue, detected in post-surgical blood samples collected before the initiation of adjuvant therapy. D DFS of patients stratified according to the presence of cfDNA harboring the same tumor-identified variants, detected in post-surgical blood samples collected during adjuvant chemotherapy