Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201)

Abstract

Background: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes.

Methods: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery.

Results: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS.

Conclusion: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC.

Trial registration: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Keywords: Adjuvant chemotherapy; Colon cancer; High-risk stage II; Inverse probability of treatment-weighting; Leucovorin; Propensity score; Risk factor; Tegafur; Uracil.

Fig. 1

Disease-free and overall survival in patients with resected high-risk stage II colon cancer. a Disease-free and b overall survival in the propensity score-matched groups. c Disease-free and d overall survival in the inverse probability of treatment weighting groups. Group A (blue): surgery alone; Group B (green): surgery followed by UFT/LV treatment. CI confidence interval, DFS disease-free survival, HR hazard ratio, OS overall survival, UFT/LV uracil, and tegafur plus leucovorin. P values were obtained using the log-rank test

Fig. 2

Hazard ratios and 95% CIs for DFS events in patients treated with surgery followed by UFT/LV treatment compared with those in patients treated with surgery alone according to baseline prognostic factors (inverse probability of treatment-weighting groups). Analyses were conducted using a Cox regression model. CI confidence interval, DFS disease-free survival, UFT/LV uracil and tegafur plus leucovorin

Fig. 3

Hazard ratios and 95% CIs for death in patients treated with surgery followed by UFT/LV treatment compared with those in patients treated with surgery alone according to baseline prognostic factors (inverse probability of treatment weighting groups). Analyses were conducted using a Cox regression model. CI confidence interval, OS overall survival, UFT/LV uracil and tegafur plus leucovorin