Biology or Technical Error? Association Between Microsatellite Instability and Positive Margins in Stage I-III Colon...

Recent Danish literature examining stage III colorectal cancer patients identified microsatellite instability (MSI) as associated with an increased risk of positive surgical margins, suggesting positive margins may reflect tumor biology rather than suboptimal technique. We sought to validate these observations using a US-based national registry.

Adults with pathologic stage I-III colon adenocarcinoma were identified in the National Cancer Database (2010-2020).

Of 105 228 patients, 21% were stage I (24% MSI), 39% II (28% MSI), and 40% III (21% MSI). MSI status was independently associated with positive margins for stage III cancers (OR 1.10, 95% CI 1.00-1.20), but not stage I and II. Positive margins were associated with worse prognosis for stage II and III cancer (HR 1.26, 95% CI 1.17-1.36; HR 1.40, 95% CI 1.33-1.48; respectively), while MSI conferred lower risk of death for stage III cancer (HR 0.87, 95% CI 0.82-0.91), but not stage I (HR 1.02, 95% CI 0.93-1.12) or II (HR 0.96, 95% CI 0.91-1.01).

This US cohort study confirmed prior European work suggesting MSI is associated with higher odds of positive margins in stage III colon cancer. Notwithstanding the limitations of a retrospective database, these findings suggest the need for quality improvement initiatives, including the evaluation of neoadjuvant treatments to mitigate this risk.