Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
BMC Cancer. 2022 Feb 15;22(1):170. doi: 10.1186/s12885-022-09267-z.
The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors.
We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm.
Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW.
Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes.
Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).
辅助化疗对于高危 II 期结肠癌（CC）的疗效尚未得到充分证实。我们比较了手术联合和不联合口服替加氟尿嘧啶（UFT/LV）治疗高危 II 期 CC 患者的效果，并对潜在的风险因素进行了调整。
我们纳入了组织学证实的 II 期结肠腺癌患者，这些患者至少有以下一种情况：T4 疾病、穿孔/穿透、低分化腺癌/黏液腺癌或<12 个淋巴结解剖。患者选择非随机或随机接受单纯手术（NR-Group S 或 R-Group S）或手术加 6 个月 UFT/LV（NR-Group U 或 R-Group U）治疗。主要终点是使用倾向评分匹配（1:2）和逆概率治疗加权（IPTW）在非随机臂中调整先前报告的风险因素后的无病生存（DFS）。
总体而言，非随机臂和随机臂分别纳入了 1902（98%）和 36（2%）例患者。随机臂患者数量太少，因此未纳入分析。在 1902 例患者中，NR-Group S 中有 402 例和 NR-Group U 中有 804 例进行了倾向评分匹配。NR-Group U 的 3 年 DFS 率（95%置信区间）显著高于 NR-Group S（80.9%[77.9%-83.4%]比 74.0%[69.3%-78.0%]）（风险比，0.64[0.50-0.83]；P=0.0006）。NR-Group S 和 NR-Group U 的 3 年总生存率无显著差异。使用 IPTW，NR-Group U 的 3 年 DFS（P=0.0013）和总生存率（P=0.0315）显著高于 NR-Group S。
对于 T4 疾病、穿孔/穿透、低分化腺癌/黏液腺癌或<12 个淋巴结解剖等至少有一项特征的高危 II 期 CC 患者，替加氟尿嘧啶辅助化疗与单纯手术相比具有显著的生存获益。
日本临床试验注册中心：jRCTs031180155（注册日期：2019 年 2 月 25 日）（UMIN 临床研究注册：UMIN000007783，注册日期：2012 年 4 月 18 日）。
