ctDNA-guided adjuvant immunotherapy in colorectal cancer

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Circulating tumor DNA (ctDNA) is a key biomarker for minimal residual disease (MRD) in colorectal cancer (CRC).
• Immunotherapy is standard for metastatic mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) CRC, but its role in earlier stages is emerging.
• Adjuvant fluoropyrimidine is not recommended for resected dMMR/MSI-H stage II CRC, and neoadjuvant therapies show diminished benefit in localized dMMR/MSI-H CRC.

Observation:

• Two cases of dMMR/MSI-H stage III colon cancer after surgery are presented.
• Adjuvant oxaliplatin-based chemotherapy failed to reduce postoperative plasma ctDNA levels in both cases.
• Switching to pembrolizumab (immune checkpoint blockade) resulted in ctDNA clearance.

Findings:

• Chemotherapy may provide suboptimal disease control for localized dMMR/MSI-H colon cancer.
• Plasma ctDNA monitoring can assess the effectiveness of adjuvant chemotherapy in clearing microscopic disease.
• Failure to clear MRD postoperatively in stage I-III CRC is associated with inevitable relapse.

Implications:

• These findings highlight the potential limitations of chemotherapy in dMMR/MSI-H colon cancer.
• Plasma ctDNA offers a dynamic tool to guide adjuvant therapy selection and monitor treatment response.
• Immune checkpoint blockade may be a viable alternative for patients with persistent ctDNA after surgery.