Assessing circulating tumour DNA (ctDNA) as a prognostic biomarker in locally advanced rectal cancer: a systematic review and meta-analysis

Abstract Introduction Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC. Methods PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS). Results Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91–16.03) and 15.15 (95% CI 8.21–27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively. Conclusion Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.