EP2013 - Serial ctDNA Analysis in Stage IV Colorectal Cancer

Purpose/Background: Circulating tumor DNA (ctDNA) has shown promise in predicting cancer recurrence earlier than conventional imaging and monitoring patient prognosis in colorectal cancer (CRC). The primary objective of this study is to evaluate the clinical utility of serial ctDNA monitoring for predicting treatment response and disease progression in stage IV colorectal cancer patients. As a secondary objective, we compared oncologic outcomes between surgery-first and chemotherapy-first approaches.

Methods/Interventions: Thirty-eight patients (chemotherapy-first: 29, surgery-first: 9) with stage IV CRC were enrolled. Serial ctDNA measurements were performed at diagnosis, after treatment initiation, and every three cycles of chemotherapy until progression.

Results/Outcomes: In this descriptive interim analysis of serial ctDNA monitoring (n=20), patients with liver-only metastases demonstrated longer progression-free periods. Initial ctDNA positivity was observed in 95% of patients, with negative conversion predominantly occurring in patients with limited metastatic burden (≤2 sites). Primary tumor resection alone did not achieve immediate ctDNA negative conversion, while metastasectomy showed more favorable ctDNA responses. All patients who never achieved negative ctDNA conversion from initial positive status experienced disease progression within three months. As a secondary outcome, survival analysis revealed that the surgery-first group demonstrated better overall survival (median survival 16mo vs no death, p=0.006) and progression-free survival (p=0.049) compared to the chemotherapy-first group.

Conclusion/Discussion: Although these are interim results, our findings suggest that ctDNA positivity serves as a promising indicator of cancer progression in stage IV CRC. Complete data analysis will be available at presentation, potentially providing stronger evidence for the role of ctDNA monitoring in treatment strategy selection.