Postoperative ctDNA Predicts Recurrence After Colorectal Cancer Liver Metastasis Resection
In 23 patients with RAS-mutant colorectal liver metastases from a phase III trial, postoperative ctDNA detected by droplet digital PCR was strongly associated with pathologic non-response and shorter recurrence-free survival. All patients with undetectable postoperative ctDNA had pathologic response, versus only 17% of ctDNA-positive patients. Despite the small cohort, the 0.88 correlation between ctDNA and pathologic response supports ctDNA as a promising non-invasive surrogate for treatment effect monitoring.
The original study
Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases.
- Authors
- Bolhuis K, van 't Erve I, Mijnals C, Delis-Van Diemen PM, Huiskens J, Komurcu A, et al.
- Journal
- EBioMedicine
- Type
- Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial
- PMID
- 34333237
Original abstract
BACKGROUND: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). METHODS: Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. FINDINGS: With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1-9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4-15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS. INTERPRETATION: The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response. FUNDING: None.