Published online Sep 27, 2026. doi: 10.4240/wjgs.120399
Revised: May 22, 2026
Accepted: July 28, 2026
Published online: September 27, 2026
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Colorectal cancer (CRC) patients with high-risk stage III disease (T4 or N2) face a significant risk of postoperative recurrence despite radical surgery and adjuvant chemotherapy. The optimal duration of capecitabine plus oxaliplatin chemo
To ascertain if postoperative ctDNA status (measured 4 weeks after surgery) predicts recurrence and guides decisions about the duration of adjuvant chemo
This is a retrospective cohort study of 50 patients with high-risk stage III CRC who received radical surgery from January 2022 to September 2025 in Foshan First People’s Hospital. All patients received adjuvant capecitabine plus oxaliplatin chemotherapy for 3 months or 6 months postoperatively. ctDNA status was assessed by next-generation sequencing 4 weeks after surgery (prior to chemotherapy administration). Patients were subsequently divided into the ctDNA-negative group (n = 29) and ctDNA-positive group (n = 21). Survival outcomes were compared to evaluate the predictive significance of ctDNA status for prognosis and its role in guiding chemotherapy across these groups.
The median follow-up was 18 months (1-43 months). The recurrence rate in the ctDNA-positive group (47.62%, 10/21) was higher than that in the ctDNA-negative group (17.24%, 5/29; P = 0.021) by November 2025. Kaplan-Meier analysis showed a significant difference in recurrence-free survival (RFS) between the two groups (Log-rank P = 0.026). Univariate Cox regression analysis revealed that tumor stage [hazard ratio (HR) = 0.172, 95% confidence interval (CI): 0.035-0.860, P = 0.032], T stage (HR = 0.212, 95%CI: 0.044-1.015, P = 0.028) and postoperative ctDNA status (HR = 6.001; 95%CI: 1.203-29.927; P = 0.029) were independent risk factors for RFS. Multivariate analysis revealed tumor stage (HR = 0.241, 95%CI: 0.079-0.739, P = 0.013) and ctDNA positivity (HR = 4.304, 95%CI: 1.412-13.115, P = 0.010) as independent predictors of disease progression in this cohort. In ctDNA-positive (P > 0.05) or ctDNA-negative (P > 0.05) individuals, stratified analysis found no significant differences between 3-month and 6-month delivery of chemotherapy in recurrence rates or RFS. The recurrence rate of ctDNA-positive patients with 3-month chemotherapy was significantly higher than that of ctDNA-negative patients with 6-month chemotherapy (50.00%, 6/12 vs 13.33%, 2/15, Log-rank P = 0.038). KRAS, TP53 and APC were the most frequently detected variants among mutation spectrum analysis across all patients.
Postoperative ctDNA status is a potent independent predictor of recurrence in high-risk stage III CRC. Notably, ctDNA status constitutes additional reference information in regard to chemotherapy duration: Based on the residual risk of recurrence, ctDNA-positive patients should be treated for 6 months to decrease this risk; conversely, amongst those with undetectable ctDNA status post-therapy, these patients could consider de-escalating treatment at 3 month without compromising outcome or safety.
Core Tip: Postoperative circulating tumor DNA (ctDNA) provides early risk stratification in high-risk stage III colorectal cancer. In this retrospective cohort of 50 patients with T4 or N2 disease, ctDNA positivity 4 weeks after surgery was independently associated with poorer recurrence-free survival and earlier recurrence, with an approximately fourfold higher adjusted recurrence risk. Exploratory analyses suggested that ctDNA status may help inform adjuvant capecitabine plus oxaliplatin duration, although no significant within-group differences were observed between 3 months and 6 months of treatment. These findings support ctDNA as a promising biomarker requiring prospective validation.