Circulating Tumor DNA Predicts Conversion Therapy Response and Prognosis in Initially Unresectable Colorectal Liver-Limited Metastases: A Retrospective Study

<b>Aims/Background</b> Effective molecular biomarkers for predicting prognosis and guiding treatment in patients with initially unresectable colorectal liver metastases (CRLMs) undergoing conversion therapy are currently lacking. This study investigated the predictive value of circulating tumor DNA (ctDNA) conversion therapy outcomes in initially unresectable CRLMs. <b>Methods</b> A retrospective analysis was conducted on 81 patients with CRLMs treated at the Sixth Affiliated Hospital, Sun Yat-sen University from January 2017 to April 2021. The relationships between baseline and treatment ctDNA levels and clinical responses were evaluated using group comparisons based on data type. The impact of ctDNA on survival outcomes was analyzed through Cox regression survival analysis. <b>Results</b> Analysis of 81 patients with ctDNA-positive at baseline showed that patients in the ctDNA low-level group had a significantly longer median progression-free survival (mPFS) (<i>p</i> = 0.039). Among 45 patients who underwent ctDNA testing during systemic therapy, the proportion of patients in the ctDNA-negative group receiving local ablative treatment (LAT) was significantly higher (70.0% <i>vs</i> 26.7%, <i>p</i> = 0.006). Furthermore, 50% of patients in the ctDNA-negative group achieved no evidence of disease (NED) status, compared to 6.7% in the ctDNA-positive group (<i>p</i> = 0.004). Both mPFS and median overall survival (mOS) were significantly longer in ctDNA-negative patients compared to ctDNA-positive patients (<i>p</i> < 0.05). Of the 61 patients who underwent LAT, 37 received ctDNA testing at the same time as imaging assessment for NED. The proportion of patients with ctDNA clearance who achieved NED status was markedly higher than that of patients with ctDNA non-clearance (78.6% <i>vs</i> 33.3%, <i>p</i> = 0.036). Patients with ctDNA clearance demonstrated significantly improved mOS compared to those with ctDNA non-clearance (not reached <i>vs</i> 30.1 months, <i>p</i> = 0.036). <b>Conclusion</b> Dynamic changes in ctDNA levels can predict both long-term survival and the effectiveness of conversion therapy in patients with initially unresectable CRLMs.