(1) Background: The duration of adjuvant chemotherapy recommended by the NCCN guidelines is 6 months. However, patients are not compliant with intravenous chemotherapy for many reasons; therefore, one approach is to obtain a survival benefit by prolonging the duration of capecitabine monotherapy. (2) Methods: A total of 355 qualified colorectal cancer (CRC) patients from January 2010 to December 2020 at West China Hospital of Sichuan University were selected to receive capecitabine monotherapy for 6–9 months and >12 months. The main endpoints were overall survival (OS) and disease-free survival (DFS). (3) Results: Among stage III patients, in the >12 months (12M) and 6–9 months (6M) groups, the 5-year DFS rates were 80.7%% and 66.8%, respectively, and the 5-year OS rates were 94.7%% and 88.8%, respectively. Among high-risk stage II patients, in the >12 months (12M) and 6–9 months (6M) groups, the 5-year DFS rates were 81.5% and 78.6%, respectively, and the 5-year OS rates were 93.1% and 84.2%, respectively. (4) Conclusions: Twelve months of chemotherapy demonstrated superior OS and DFS to that of six months in the stage III group but showed no difference in the high-risk stage II group. The better OS and DFS observed in the 12-month treatment period could be of value in selected cases.
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