Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial
Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial
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DOI：
10.1200/jco.18.02059
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发表时间：
2019-08-01
影响因子：
45.3
通讯作者：
Sugihara, Kenichi
中科院分区：
文献类型：
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作者：
Ueno, Hideki;Ishiguro, Megumi;Sugihara, Kenichi
国际抗癌联盟强调肿瘤出芽是肿瘤相关的预后因素。肿瘤出芽的国际评估标准最近由2016年国际肿瘤出芽共识会议（ITBCC 2016）定义。本研究旨在阐明肿瘤出芽的预后和预测价值，在一项随机对照试验中，评价口服替加氟尿嘧啶辅助化疗优于单独手术治疗II期结肠癌（SACURA试验; ClinicalTrials.gov标识符：NCT 00392899）。根据ITBCC 2016中采用的标准，通过中心审查诊断肿瘤出芽。我们前瞻性地记录了所有的临床和病理数据，包括萌芽级别，并在完成患者登记5年后进行预后分析。5年无复发生存率（RFS）分别为90.9%、85.1%和74.4%（P <0.001），T4肿瘤的范围很广（86.6%~ 53.3%）。芽殖分级与肝、肺、淋巴结和腹膜的复发显著相关（P <0.001至0.01）。多变量分析表明，芽期和T期对RFS有独立影响，根据Harrell一致性指数，这两个因素对预测RFS的考克斯模型的改进有显著贡献。BD 2和BD 3组的5年复发率在辅助化疗组比单纯手术组提高了约5%，但差异无统计学意义。CONCLUSION根据ITBCC 2016标准进行的肿瘤出芽分级应在病理实践中进行常规评估，并可提高II期结肠癌辅助化疗的获益。
PURPOSEThe International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899).PATIENTS AND METHODSBetween 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients' registration.RESULTSOf 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively (P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum (P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant.CONCLUSIONTumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.