Presurgical levels of circulating tumour DNA in patients with resectable chemotherapy-naïve colorectal liver metastases: association with multiorgan recurrence and survival in the MIRACLE cohort.

BACKGROUND

Almost half of patients with colorectal liver metastases (CRLM) experience disease recurrence within one year after treatment with curative intent. To improve treatment, upfront identification of patients with CRLM at high risk of rapid disease recurrence is crucial.

METHODS

In this retrospective cohort-study, pretreatment ctDNA levels were determined by the modified fast aneuploidy screening test-sequencing system (mFast-SeqS) in 182 patients with resectable CRLM who did not receive perioperative chemotherapy. Resulting aneuploidy scores were dichotomized using a predefined threshold and associated with clinical outcome.

RESULTS

Of 182 analysed patients, 34 (19%) were classified as ctDNA high and 156 (81%) as ctDNA low. Recurrence-free (RFS) and overall survival (OS) were shorter in the ctDNA high versus low group, with 1-year RFS of 29% versus 52%, and 3-year OS of 48% versus 78% respectively (log-rank P = 0.029 and < 0.001 respectively). The cumulative incidence of multiorgan recurrence within the first year after local treatment was significantly higher in ctDNA-high patients (Gray's test P < 0.001). Multivariable Cox regression analysis revealed that the aneuploidy score is independently associated with RFS (HR = 1.94; 95% c.i. 1.19 to 3.18) and multiorgan RFS up to 1 year (HR = 2.56; 95% c.i. 1.41 to 4.65) and OS up to 3 years (HR = 3.28; 95% c.i. 1.79 to 6.01).

CONCLUSIONS

This study shows that mFast-SeqS provides an affordable and minimally invasive test for the upfront recognition of patients with CRLM at increased risk of rapid (multiorgan) disease recurrence.