Treatment of Non-Metastatic Resectable Colon Cancer with dMMR/MSI-H Status or POLE/POLD1 Ultra-Hypermutated Phenotype
This protocol addresses a molecularly distinct subgroup of colon cancer defined by its mismatch repair and mutational characteristics. Understanding the appropriate post-surgical management in this setting requires careful stage-by-stage evaluation guided by current evidence.
Clinical Scenario
Patients with colon cancer that is MMR deficient (dMMR) or MSI-high (MSI-H), or that harbours a POLE/POLD1 mutation conferring an ultra-hypermutated phenotype (e.g., TMB >50 mut/Mb). The tumour is non-metastatic and resectable, without obstruction.
Adjuvant Management — Partial Overview
Following surgical resection, adjuvant management in this molecularly defined population is determined by pathologic stage. Earlier-stage disease may be managed with observation alone, while higher-risk stages may involve adjuvant systemic therapy — including, in certain scenarios, regimens that incorporate an immunotherapy agent alongside chemotherapy. Additional pathway-specific findings at staging may also inform treatment decisions beyond the core regimen.
The complete stage-stratified regimen options, selection criteria, and all applicable considerations are available in the full structured protocol.
References
- dMMR/MSI-H or POLE/POLD1 mutation with ultra-hypermutated phenotype (eg, TMB >50 mut/Mb) colon cancer (non-metastatic)
- Resectable, non-obstructing
- Observation
- Consider adjuvant systemic therapy as for low-risk stage III disease
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