局部进展期直肠癌新辅助治疗的研究进展

Research progress of neoadjuvant therapy for locally advanced rectal cancer

随着口服氟尿嘧啶类及靶向类等多种新型药物的临床应用，术前精准影像学分期的开展，最新的美国国立综合癌症网络（NCCN）指南和目前欧洲临床肿瘤学会（ESMO）指南建议的局部进展期直肠癌（LARC）新辅助治疗的适应证标准面临诸多挑战，值得再审视。通过口服卡培他滨代替氟尿嘧啶静脉输液，联用其他化疗药增强现有方案，以及对部分患者采用单纯新辅助化疗是否可以替代标准新辅助放化疗都是目前新辅助治疗方案的延伸热点。传统的新辅助治疗疗效评价更重视治疗对病理完全缓解（pCR）率的影响，然而，目前的研究则倾向于将术后无病生存期（DFS）作为更为重要的评价指标。此外，寻找对新辅助治疗有预测性及整体生存有预后性的生物标志物一直都是直肠癌新辅助治疗领域的研究热点。等待观察策略（watch and wait）系指对于新辅助治疗后获得临床完全缓解（cCR）的患者采取严密随访的策略代替直接手术，但当下对新辅助治疗后cCR的评价时间及标准尚无统一定论。因此，目前关于新辅助治疗在LARC的临床应用方面还存在很多争议。故本文围绕新辅助治疗适应证的再审视、方案的延伸、疗效评价和新辅助治疗与等待观察策略，以及其他热点问题对LARC新辅助治疗领域的研究进展做一综述。

The clinical application of novel chemotherapeutic drugs including oral 5-FU and targeted drugs and preoperatively accurate imaging grading has brought challenges to the indication criteria developed by NCCN and ESMO for neoadjuvant chemoradiotherapy in locally advanced rectal cancer （LARC） . Extended hotspots have focused on the effectiveness of using capecitabine instead of fluorouracil infusion, the combination of multiple drugs and the feasibility of using neoadjuvant chemotherapy instead of neoadjuvant chemoradiotherapy for selective patients. Traditionally, the evaluation of the effect of neoadjuvant therapy has been based on the effect on the pathological complete remission （pCR） rate. However, current studies recommend the disease-free survival （DFS） as a more important outcome. Besides, seeking for effective biomarkers as predictive markers for neoadjuvant therapies or as prognostic markers remains a hotspot in the field of neoadjuvant chemoradiotherapy. The ＂watch and wait＂ approach refers to taking a close follow-up strategy instead of direct operation for patients achieving clinically complete remission （cCR） after neoadjuvant therapy. However, there is no unified evaluation criteria and time point for the evaluation of cCR following neoadjuvant therapy. Therefore, there remain a lot of controversies regarding the clinical application of neoadjuvant chemoradiotherapy in LARC. In this manuscript, research progress in the indication for neoadjuvant therapy, improvement in the neoadjuvant therapeutic schedule, advancement of the efficacy evaluation criteria of neoadjuvant therapy, the ＂watch and wait＂ approach and other hot topics is summarized to provide references for clinical practice.