Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Xuhui District, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Xuhui District, Shanghai, 200032, China.
BMC Cancer. 2019 Nov 15;19(1):1117. doi: 10.1186/s12885-019-6289-6.
The CAO/ARO/AIO-94 demonstrated that neoadjuvant chemoradiotherapy (CRT) could decrease the rate of local recurrence rather than distal metastases in advanced rectal cancer. Adjuvant chemotherapy (ACT) can eliminate micrometastasis, and render a better prognosis to rectal cancer. However, adoption of ACT mainly depends on the evidence from colon cancer. Neoadjuvant CRT can lead to tumor shrinkage in a number of patients with advanced rectal cancer. The administration of adjuvant therapy depending on pretreatment clinical stage or postoperative yield pathological (yp) stage remains controversial. At present, the clinical guidelines recommend ACT for patients with stage II/III (ypT3-4 N0 or ypTanyN1-2) rectal cancer following neoadjuvant CRT and surgery. However, the yp stage may influence the guidance of ACT.
According to the postoperative pathological stage, the present study was divided into two parts with different study design procedures. Patients will undergo different therapeutic strategies after collecting data related to postoperative pathological stage. For patients with pathologic complete response or yp stage I, the study was designed as a non-inferiority trial to compare the patients' long-term outcomes in observational group and those in treatment group with 5-fluorouracil. For patients at yp stage II or III, the study was designed as a superiority trial to compare the oncological effect of oxaliplatin combined with 5-fluorouracil, in addition to 5-fluorouracil alone in ACT. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints are 3-year, 5-year overall survival, 5-year DFS, and the rate of local recurrence and adverse events resulted from chemotherapy and the patients' quality of life postoperatively.
The ACRNaCT trial aims to investigate whether observation is not inferior than 5-fluorouracil for pathologic complete response or yp stage I, and indicate whether combined chemotherapy contains superior outcomes than 5-fluorouracil alone for yp stage II or III in patients receiving neoadjuvant CRT and surgery for locally advanced rectal cancer (LARC). This trial is expected to provide individualized adjuvant treatment strategies for LARC patients following neoadjuvant CRT and surgery.
The trial has been registered in ClinicalTrials.gov on January 30, 2018 (Registration No. NCT03415763), and also, that was registered in Chinese Clinical Trial Registry on November 12, 2018 (Registration No. ChiCTR1800019445).
CAO/ARO/AIO-94 研究表明，新辅助放化疗（CRT）可降低局部复发率，而不是晚期直肠癌的远处转移率。辅助化疗（ACT）可以消除微转移，从而改善直肠癌的预后。然而，ACT 的采用主要取决于结肠癌的证据。新辅助 CRT 可使许多晚期直肠癌患者的肿瘤缩小。根据术前临床分期或术后病理（yp）分期给予辅助治疗的方法仍存在争议。目前，临床指南建议对接受新辅助 CRT 和手术的 II/III 期（ypT3-4N0 或 ypTanyN1-2）直肠癌患者进行 ACT。然而，yp 分期可能会影响 ACT 的指导。
根据术后病理分期，本研究分为两部分，采用不同的研究设计程序。收集与术后病理分期相关的数据后，患者将接受不同的治疗策略。对于病理完全缓解或 yp Ⅰ期的患者，本研究设计为非劣效性试验，比较观察组和治疗组（5-氟尿嘧啶）患者的长期结局。对于 yp Ⅱ期或Ⅲ期的患者，本研究设计为优效性试验，比较奥沙利铂联合 5-氟尿嘧啶与单纯 5-氟尿嘧啶在 ACT 中的抗肿瘤效果。主要终点是 3 年无病生存率（DFS）。次要终点是 3 年、5 年总生存率、5 年 DFS、局部复发率和化疗相关不良事件发生率以及术后患者生活质量。
ACRNaCT 试验旨在探讨病理完全缓解或 ypⅠ期患者观察是否不劣于 5-氟尿嘧啶，以及接受新辅助 CRT 和手术的局部晚期直肠癌（LARC）患者 ypⅡ或Ⅲ期患者联合化疗是否优于单纯 5-氟尿嘧啶。该试验有望为接受新辅助 CRT 和手术的 LARC 患者提供个体化的辅助治疗策略。
该试验于 2018 年 1 月 30 日在 ClinicalTrials.gov 注册（注册号：NCT03415763），并于 2018 年 11 月 12 日在中国临床试验注册中心注册（注册号：ChiCTR1800019445）。
