Typically, most patients with mCRC are incurable. However, a minority of patients who undergo complete metastasectomy attain cure. In particular, up to 75% of oligometastatic CRC patients develop recurrence post-resection. Existing data in the oligometastatic setting has shown that the efficacy of postoperative adjuvant treatment is limited and is largely extrapolated from earlier stages. Establishing prognosis after oligometastatic resection is difficult and thus a need exists for a better prognostic marker. Circulating tumour DNA (ctDNA) has been shown to identify minimal residual disease (MRD) and the risk of recurrence in early-stage disease. In this study, we present the largest clinical experience of MRD testing in the oligometastatic setting.
Tumour tissue and serial plasma samples were collected from CRC patients undergoing resection of metastases with curative intent as part of the PREDATOR study. A personalized and tumour-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA for post-resection MRD assessment. The study evaluated the prognostic value of ctDNA correlating MRD status with clinical outcomes.
A total of 100 patients were analysed. Post-oligometastatic resection, adjuvant therapy was given to 38% of the patients at the discretion of the treating physician. Post-surgery, MRD-positivity was observed in 52% (52/100) of patients, of which 86.5% (45/52) eventually relapsed (HR: 4.6; 95%CI: 2.6-8.1; P<0.001). MRD-positive status was also associated with an inferior overall survival (HR: 22.0; 95%CI: 3.0-166.0, P=0.002). At the time of the analyses, in the MRD-negative arm, 98% of patients were alive compared to 57.7% in the MRD-positive arm. In the multivariate analysis, ctDNA status was the most significant prognostic factor associated with PFS (HR: 4.59, 95% CI: 2.51-8.4; P<0.001).
This study validates personalized ctDNA-based MRD status as the most significant biomarker for prognosis in patients with oligometastatic CRC. This biomarker may offer the clinical utility of guiding adjuvant treatment decisions in the oligometastatic setting and of informing future trial design.
Clinical trial identification
Legal entity responsible for the study
F. Loupakis: Advisory/Consultancy: Amal. S. Sharma, D. Renner, S. Shchegrova, H. Sethi, B. Zimmermann, A. Aleshin: Full/Part-time employment: Natera. All other authors have declared no conflicts of interest.