Curative Intent, Local Therapy, and ctDNA in MSI-H Metastatic Colorectal Cancer

This segment explores how durable responses to immunotherapy are reshaping the role of surgery and local therapies in patients with MSI-H/dMMR mCRC who have limited disease burden. The discussion begins with a practical and philosophical question: in the era of highly effective checkpoint inhibition, how should clinicians contextualize curative intent, and are some patients achieving outcomes consistent with cure?

Panelists reflect on long-term follow-up data from immunotherapy trials, noting that radiographic assessment alone can be misleading in MSI-H disease. Residual lesions may persist on CT imaging despite deep and durable responses, often representing fibrosis rather than active tumor. PET imaging can add value but remains imperfect, prompting growing interest in ctDNA as an adjunctive decision-making tool.

The group highlights real-world experience using ctDNA to help determine whether ongoing immunotherapy is necessary or whether treatment can safely be stopped after prolonged disease control, particularly in patients receiving nivolumab-based therapy. ctDNA negativity has been increasingly used to support treatment de-escalation and avoid unnecessary surgery or prolonged systemic therapy in patients without symptoms or metabolic activity on imaging.

The conversation also touches on emerging strategies such as nonoperative management and organ-sparing approaches, which were previously uncommon in mCRC. Faculty emphasize that increasing institutional experience and published data are making these approaches more acceptable, with anticipation that they may eventually be reflected in NCCN guidelines.

Finally, the panel references early data suggesting that ctDNA assessment as early as 30 days after initiation of immunotherapy may help predict long-term outcomes, including complete response. This evolving integration of molecular monitoring underscores a shift toward more personalized, biology-driven decisions regarding surgery, local therapy, and curative intent in MSI-H mCRC.