ctDNA Predicts Early Multiorgan Recurrence in CRLM : BJS | May 2026

Introduction

Colorectal Liver Metastases frequently recur despite curative-intent surgery, with nearly half of patients developing relapse within the first postoperative year. Early identification of biologically aggressive disease remains a major unmet need in surgical oncology.

Problem Statement

Reliable preoperative biomarkers capable of identifying patients with resectable colorectal liver metastases at high risk for rapid multiorgan recurrence and poor survival are lacking.

Summary

This MIRACLE cohort study evaluated pretreatment circulating tumour DNA using the modified fast aneuploidy screening test-sequencing system (mFast-SeqS) in chemotherapy-naïve patients undergoing curative-intent treatment for colorectal liver metastases.

Patients with high pretreatment ctDNA aneuploidy scores experienced markedly worse oncologic outcomes compared with ctDNA-low patients. Recurrence-free survival and overall survival were both significantly reduced, with ctDNA-high patients demonstrating substantially higher rates of rapid relapse.

Most notably, elevated ctDNA was strongly associated with early multiorgan recurrence within the first postoperative year. This finding is clinically important because multiorgan relapse often reflects occult systemic dissemination not fully captured by conventional imaging or clinicopathologic risk models.

The prognostic value of ctDNA remained independently significant on multivariable analysis for recurrence-free survival, multiorgan recurrence and overall survival, reinforcing its role as a robust biologic marker of aggressive metastatic disease.

Importantly, the study focused specifically on chemotherapy-naïve patients, reducing confounding effects from perioperative systemic treatment and providing a clearer assessment of baseline tumour biology.

A major practical strength of the work is the use of mFast-SeqS, an affordable and minimally invasive sequencing platform based on genome-wide aneuploidy detection rather than individualized mutation tracking. This may improve scalability and real-world implementation compared with more complex personalized ctDNA assays.

The findings support the growing concept that ctDNA reflects minimal residual systemic disease burden even before surgery. Elevated pretreatment ctDNA likely identifies patients with biologically disseminated micrometastatic disease despite technically resectable liver metastases.

Clinically, these results may eventually influence perioperative decision-making. Patients with high ctDNA burden could potentially benefit from intensified systemic therapy, closer surveillance or alternative multimodal treatment strategies rather than surgery alone.

The association with multiorgan recurrence is particularly relevant because current surgical selection criteria rely heavily on anatomical resectability and radiologic disease burden, which incompletely capture tumour biology.

This study therefore contributes to the ongoing transition from anatomy-based toward biology-driven management of metastatic colorectal cancer.

The findings also align with broader precision oncology trends where liquid biopsy technologies increasingly guide risk stratification, treatment escalation and postoperative surveillance strategies across solid tumors.

Future studies will need to determine whether ctDNA-guided perioperative treatment adaptation can improve outcomes and whether serial postoperative monitoring further refines recurrence prediction.

Importantly, prospective validation and integration with molecular, radiologic and clinicopathologic risk models will be essential before widespread implementation into routine surgical oncology practice.

Overall, this MIRACLE cohort study demonstrates that elevated pretreatment ctDNA measured by mFast-SeqS independently predicts rapid multiorgan recurrence and inferior survival in resectable colorectal liver metastases, supporting ctDNA as a promising biomarker for biologic risk stratification before curative-intent surgery.