Yamadera M, et al. - Researchers conducted a retrospective study of 2 cohorts of patients with microsatellite-stable stage III colorectal cancer with curatively intended surgery (R0) from 1999 to 2005 (first cohort; n = 203) and 2006 to 2012 (second cohort; n = 346) in order to assess the clinical benefits of adjuvant chemotherapy according to the tumor budding status in these patients. In the two cohorts, 5-fluorouracil–based adjuvant chemotherapy was administered to 128 and 203 patients and but not to 75 and 143 patients, respectively. In low-budding tumors, they observed better cancer-specific survival in the chemotherapy group vs the surgery-alone group (first cohort, 93.1% vs 65.5%; second cohort, 94.0% vs 76.0%). Conversely, in high-budding tumors, the statistically insignificant prognostic difference was observed between the chemotherapy and surgery-alone groups (first cohort, 59.7% vs 52.4%; second cohort, 83.1% vs 75.6%). Findings here suggest resistance to 5-fluorouracil–based chemotherapy in the high-budding group, whereas significant survival benefits from adjuvant chemotherapy in the low-budding group in stage III colorectal cancer.