Wang Y, Yang L, Bao H, et al. - Improved prediction of pathological complete response (pCR)/non-pCR after neoadjuvant chemoradiotherapy (nCRT) is afforded by the model combining circulating tumor DNA (ctDNA) and magnetic resonance imaging (MRI) for locally advanced rectal cancer (LARC) patients receiving nCRT followed by total mesorectal excision (TME). ctDNA affords a tool that can supplement MRI to better predict nCRT response, as well as can potentially aid selection of candidates for nonoperative treatment and guide the management approach for those with different recurrence risks.

• A prospective cohort study of 119 LARC patients receiving nCRT followed by TME.

• At baseline, during nCRT, and post-surgery, a total of 531 serial plasma samples were obtained.

• Next-generation sequencing was conducted using a panel comprising 422 cancer-related genes.

• A significant correlation of baseline ctDNA features, as well as of the clearance of ctDNA during nCRT, with pCR status was evident.

• Predictive models based on ctDNA alone, MRI alone, and combination of ctDNA and MRI were developed, and it was revealed that the combining model showed significantly better performance in predicting pCR/non-pCR vs ctDNA alone or MRI alone.

• Identification of potential colorectal cancer driver genes in ctDNA post-nCRT suggested a significantly worse recurrence-free survival (hazard ratio = 9.29).

• Cases with a high risk of recurrence can be stratified by combining ctDNA with HR_feature (high-risk feature).