Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for...

Area of Science:

• Oncology
• Gastroenterology
• Genetics

Background:

• Colon cancers exhibit distinct clinical and pathological features based on microsatellite instability (MSI) status.
• High-frequency MSI (MSI-H) tumors differ significantly from microsatellite-stable (MSS) tumors.
• Understanding MSI's role is crucial for optimizing adjuvant chemotherapy in stage II and III colon cancer.

Purpose of the Study:

• To evaluate the utility of MSI status as a predictive biomarker for adjuvant chemotherapy response.
• To determine if fluorouracil-based adjuvant chemotherapy benefits stage II and III colon cancer patients with MSI-H tumors.
• To compare treatment outcomes between MSI-H and MSS/low-frequency MSI (MSI-L) colon cancer patients receiving adjuvant chemotherapy.

Main Methods:

• Tumor specimens were analyzed from patients with stage II/III colon cancer enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy.
• Microsatellite instability was assessed using both mononucleotide and dinucleotide markers.
• Overall survival rates were compared between patients with different MSI statuses, with and without adjuvant chemotherapy.

Main Results:

• Of 570 specimens, 16.7% showed high-frequency MSI (MSI-H).
• In patients not receiving adjuvant therapy, MSI-H tumors were associated with better five-year overall survival (HR, 0.31; P=0.004).
• Adjuvant chemotherapy did not improve survival in MSI-H patients (HR, 1.07; P=0.80), but significantly benefited MSS/MSI-L patients (HR, 0.72; P=0.04).

Conclusions:

• Fluorouracil-based adjuvant chemotherapy is beneficial for stage II/III colon cancer patients with MSS or MSI-L tumors.
• Patients with MSI-H tumors do not benefit from fluorouracil-based adjuvant chemotherapy.
• MSI status is a critical predictive biomarker for guiding adjuvant chemotherapy decisions in colon cancer.