EP712 - Impact of Chemotherapy on Survival Outcomes in Microsatellite Unstable Stage II and III Colon Cancer

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Purpose/Background: The prognostic impact of adjuvant chemotherapy (adjCT) on microsatellite instability (MSI) status in stage II and III colon cancer remains controversial. In this study, we aimed to evaluate and compare overall survival rates in patients with microsatellite unstable (MSI-U) stage II and III colon cancer based on their adjuvant adjCT status.

Methods/Interventions: Patients diagnosed with histopathological stage II and III colon cancer who underwent colectomy between 2013 and 2019 were identified from the National Cancer Database (NCDB) using ICD-O-3 codes (8140-47, 8210-11, 8220-21, 8255, 8260-63, 8480-81, 8490, C18.0, C18.2-18.7). The MSI-U colon cancer group encompasses cases classified as MSI-high; positive, MSI-low; positive, and MSI-Not otherwise specified; positive in the NCDB variables. Stage II patients were classified as high risk if they met any of the following criteria: pathological stage T4, lymphovascular invasion, perineural invasion, high grade, fewer than 12 regional lymph nodes examined, or residual tumor at surgical margins. Other patients without these criteria were classified as low risk. Demographic and pathological characteristics were compared between the patients with high-risk and low-risk stage II MSI-U and stage III MSI-U colon cancer, categorized by adjCT status. Propensity score matching was used to adjust for confounding variables between the groups, ensuring a more accurate comparison of survival outcomes. Kaplan-Meier analyses were then performed to assess 3- and 5-year overall survival rates between those who received adjCT and those who did not.

Results/Outcomes: In this study, we identified 56,913 MSI-stable (MSI-S) patients and 19,506 patients with MSI-U stage II and III colon cancer . Of the MSI-U cohort, 11,426 (58.6%) were stage II and 8,080 (41.4%) were stage III patients who met the final analysis inclusion criteria. The MSI-U cohort demonstrated a significant female predominance (57.9%, n=13,302; p< 0.01) and was predominantly Caucasian (86.3%, n=16,829; p< 0.01). Histologically, MSI-U tumors showed a higher proportion of mucinous adenocarcinoma (16.0%, n=3,113) compared to MSI-S tumors (7.2%, n=4,105; p< 0.01).

adjCT administration varied by risk stratification: 16% (n=813) of high-risk stage II MSI-U patients (n=5,030) received adjCT, compared to 5% (n=347) of low-risk stage II MSI-U patients (n=6,396). In stage III MSI-U patients (n=8,080), 67% (n=5,385) of them received adjCT . In high-risk MSI-U stage II patients, significant differences were found between those who received adjCT (n=813) and those who did not (n=4,217) in tumor grade (G1-G2: 37.0% vs. 54.6%; G3-G4: 63.0% vs. 45.4%), pT stage (T4: 24.7% vs. 54.1%), and surgical margin status (residual tumor: 3.5% vs. 10.7%), along with additional diffevrences in age and Charlson-Deyo score.

Five-year overall survival (OS) analysis showed that high-risk stage II patients had significantly improved survival with adjCT (82% vs. 69%; p< 0.001). The most significant survival benefit was observed in stage III MSI-U patients receiving adjCT (67% vs. 38%; p< 0.001). Low-risk stage II MSI-U patients indicated a non-significant survival advantage with adjCT (87% vs. 83%; p=0.055).

Conclusion/Discussion: This large-scale analysis of the NCDB data revealed a survival benefit of adjCT in patients with stage II MSI-U colon cancer with high risk factors and in patients with stage III MSI-U colon cancer. These findings support a risk-stratified approach to adjuvant therapy in MSI-U colon cancer.