Circulating DNA in Rectal Cancer to Unravel the Prognostic Potential for Radiation Oncologist: A Meta-analysis.

Objectives: Liquid biopsy, with its noninvasive nature and ability to detect tumor-specific genetic alterations, emerges as an ideal biomarker for monitoring recurrences for locally advanced rectal cancer (LARC). Completed studies have small sample sizes and different experimental methods. To consolidate and assess the collective evidence regarding the prognostic role of circulating DNA (ctDNA) detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT).

Methods: Computerized bibliographic searches of MEDLINE and CANCERLIT (2000 to 2023) were supplemented with hand searches of reference lists. Study selection: studies evaluating oncological outcomes of patients with LARC treated with a nCRT comparing patients with positive and negative liquid biopsy at baseline and after nCRT. Data extraction: data on population, intervention, and outcomes were extracted from each study, in accordance with the intention to treat method, by 2 independent observers, and combined using the DerSimonian method and Laird method.

Results: Nine studies follow inclusion criteria including 678 patients treated with nCRT. The pooled RD rate of ctDNA negative between measure at baseline and after nCRT is statistically significant 61% (95% CI: 53-70, P=0.0002). The hazard ratio (HR) of progression-free survival between ct-DNA negative and positive is significant 7.41 (95% CI: 4.87-11.289, P<0.00001).

Conclusions: ctDNA can identify patients with different recurrence risks following nCRT and assess prognosis in patients with LARC. Further prospective study is necessary to determine the utility of ctDNA in personalised therapy for patients with LARC.