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.2011.40.1836
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发表时间：
2012-06-01
影响因子：
45.3
通讯作者：
Roedel, Claus
中科院分区：
文献类型：
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作者：
Sauer, Rolf;Liersch, Torsten;Roedel, Claus
目的在2004年发表的CAO/ARO/AIO-94[外科肿瘤学工作组/放射肿瘤学工作组/内科肿瘤学工作组]试验的初步结果显示，局部控制率提高后，术前放化疗(CRT)已被确立为局部晚期直肠癌的标准治疗方法。然而，在中位数46个月的随访后，没有显示出生存益处。823例II~III期直肠癌患者随机分为术前CRT联合氟尿嘧啶(FU)组、全直肠系膜切除组和辅助性FU组，或术后CRT组。这项研究被设计为有80%的力量来检测作为主要终点的5年总存活率10%的差异。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率。结果在799名符合条件的患者中，404名患者被随机分配到术前，395名患者被随机分配到术后CRT。按意向处理分析，手术前和术后10年生存率分别为59.6%和59.9%(P=.85)。10年累计局部复发率分别为7.1%和10.1%(P=0.048)。两组患者10年累积远处转移率(29.8%和29.6%；P=0.9)和无瘤生存率无显著差异。结论CRT治疗前后局部控制率持续显著提高，但对总体生存率无明显影响。在CAO/ARO/AIO-04试验中，将更有效的系统治疗整合到多模式治疗中，以可能减少远处转移和提高存活率。
PurposePreoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months.Patients and MethodsA total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival.ResultsOf 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival.ConclusionThere is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.