Nature medicine 2024 Sep 16
ctDNA-based molecular residual disease and survival in resectable colorectal cancer.
Abstract
The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.
Related Questions
Why does NCCN still not recommend using circulating tumor DNA to guide adjuvant chemotherapy in stage II colon cancer when colon cancer experts are currently embracing the practice?
While I cannot speak to that panel itself, I can support the very rigorous process that all NCCN guidelines undergo, and I surmise that the reason why ctDNA is not yet recommended is because there is no consensus that: It is better than CEA and good quality cross-sectional imaging (see, for example,...
Are there any adverse risk factors in stage I colon cancer that would warrant ctDNA testing?
I would not check ctDNA in this setting. If there is an adverse feature of the tumor and the patient is a candidate for further treatment, I would do close surveillance imaging and CEA at the most. A recent publication of a larger cohort study of stage II to IV resected colorectal cancer suggests th...
Would you offer chemotherapy to an elderly patient with MSI-H stage 3 colon cancer who cannot tolerate oxaliplatin?
The current NCCN guidelines already incorporated the ATOMIC study data and added CAPOX or FOLFOX with atezolimumab in addition to CAPOX or FOLFOX as preferred regimens for resected dMMR stage III colon cancer, while still listing single-agent fluoropyrimidine as an option.The interesting part to me ...