Treatment of Colon Cancer with dMMR/MSI-H or POLE/POLD1 Ultra-Hypermutation — Resectable, Non-Metastatic
This protocol covers non-metastatic colon cancer that is amenable to surgical resection in patients whose tumours are mismatch-repair deficient (dMMR) or microsatellite instability-high (MSI-H), or carry a POLE or POLD1 mutation producing an ultra-hypermutated phenotype (e.g., tumour mutational burden >50 mut/Mb). This molecular profile is central to treatment planning.
Clinical Scenario
The patient has colon cancer confirmed to be:
dMMR / MSI-H
POLE/POLD1 mutation
Ultra-hypermutated (TMB >50 mut/Mb)
Non-metastatic
Resectable
The tumour is resectable and non-obstructing. Depending on local tumour extent, the therapeutic approach prior to surgery may differ.
Treatment Approach (overview only)
The cornerstone of management is surgical resection — colectomy with en bloc removal of regional lymph nodes. For tumours with greater local extent, a course of therapy given before surgery may be considered; in this molecularly defined subgroup, checkpoint inhibitor immunotherapy plays a prominent role among the neoadjuvant options evaluated. The full regimen, complete decision algorithm, and tumour-extent-specific pathways are available in the structured protocol below.
References
- dMMR/MSI-H or POLE/POLD1 mutation with ultra-hypermutated phenotype (eg, TMB >50 mut/Mb) colon cancer (non-metastatic)
- Resectable, non-obstructing
- Colectomy with en bloc removal of regional lymph nodes
- Consider neoadjuvant checkpoint inhibitor immunotherapy (for T4 or bulky primary) (COL-D 5 of 17)
- Consider neoadjuvant therapy: Checkpoint inhibitor immunotherapy (preferred) (COL-D 5 of 17)
View source ↗