Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.
Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.
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DOI：
10.1200/jco.2011.29.15_suppl.3516
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
R. Sauer;T. Liersch;S. Merkel;H. Becker;W. Hohenberger;H. Witzigmann;C. Hess;R. Fietkau;C. Wittekind;C. Roedel
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文献类型：
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作者：
R. Sauer;T. Liersch;S. Merkel;H. Becker;W. Hohenberger;H. Witzigmann;C. Hess;R. Fietkau;C. Wittekind;C. Roedel
3516背景：CAO/ARO/AIO-94于2004年发表，中位随访时间为46个月（Sauer et al., N Engl J Med 2004）。该试验基于5年局部控制率的改善，确立了术前CRT作为直肠癌的标准治疗方法，然而，没有显示出生存获益。我们在此报告中位随访时间为134个月的结果。方法：我们将823例II期或III期直肠癌患者随机分配到术前CRT (50.4 Gy) + 5-FU （1 g/msq/天1-5、29-33）、手术和辅助5-FU （500 mg/msq/天1-5、4个周期），或术后应用相同的方案。该研究的主要终点是5年总生存期（5年总生存期）差异为10%，其检测能力为80%。次要终点包括局部和远处复发的累积发生率以及无病生存期。结果823例患者中，404例和395例随机分为术前和术后CRT组；24人不符合条件，38人要求改变治疗组。406例患者术前接受CRT治疗，393例患者术后接受CRT治疗。截至2010年12月，799名符合条件的患者中分别有791名和783名患者的生命和肿瘤状态更新数据。术前组10年总生存率为59.9年（95% CI, 55.0-64.8%），术后组为59.5% (95% CI, 54.6-64.4%)（根据治疗意向，log-rank检验p=0.86）。宏观完全切除后10年累积局部复发发生率在术前和术后组分别为5.7% （95% CI, 3.2-8.2%）和10.4% (95% CI, 7.1-13.4%) （p=0.009， log-rank检验，根据实际治疗情况）。10年累积远处转移发生率（均为25.5%,p=0.88）和DFS无显著差异。结论：与术后相比，术前CRT对局部控制有持续的显著改善，但对总生存没有影响。在CAO/ARO/AIO-04试验中，将更有效的全身治疗整合到联合治疗中，可能会减少远处转移并提高生存率。
3516 Background: CAO/ARO/AIO-94 was published in 2004 with a median follow-up of 46 months (Sauer et al., N Engl J Med 2004). This trial established preoperative CRT as standard treatment for rectal cancer based on an improved local control rate at 5 years, however, no survival benefit could be shown. We here report results with a median follow-up of 134 months. METHODS We randomly assigned 823 patients with stage II or III rectal cancer to preoperative CRT (50.4 Gy) with 5-FU (1 g/msq/days 1-5, 29-33), surgery, and adjuvant 5-FU (500 mg/msq/days 1-5, 4 cycles), or the same schedule applied postoperatively. The study was designed to have 80% power to detect a difference of 10% in the 5-year overall survival as primary endpoint. Secondary endpoints included the cumulative incidence of local and distant relapses and disease-free survival. RESULTS Of 823 patients, 404 and 395 were randomized to preoperative and postoperative CRT, respectively; 24 were ineligible, and 38 requested a change in treatment group. Thus, 406 patients received preoperative CRT, 393 were treated in the postoperative arm. As of 12/2010, updated data for life and tumor status were available for 791 and 783 of 799 eligible patients, respectively. Overall survival at 10 years was 59.9 years (95% CI, 55.0-64.8%) in the preoperative arm, and 59.5% (95% CI, 54.6-64.4%) in the postoperative arm (p=0.86, log-rank test, according to intention to treat). The 10-year cumulative incidence of local relapse after macroscopically complete resection was 5.7% (95% CI, 3.2-8.2%) and 10.4% (95% CI, 7.1-13.4%) in the pre- and postoperative arms, respectively (p=0.009, log-rank test, according to actual treatment). No significant differences were detected for 10-year cumulative incidence of distant metastases (25.5% both, p=0.88) and DFS. CONCLUSIONS There is a persisting significant improvement of pre- vs. postoperative CRT on local control, however, no effect on overall survival. Integrating more effective systemic treatment into the combined modality treatment has been adopted in trial CAO/ARO/AIO-04 to possibly reduce distant metastases and improve survival.