University College London Hospitals NHS Foundation Trust, 235 Euston Rd, London, NW1 2BU, UK.
Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Rickmansworth Rd, Northwood, HA6 2RN, UK.
Curr Treat Options Oncol. 2022 Apr;23(4):453-473. doi: 10.1007/s11864-022-00961-5. Epub 2022 Mar 21.
The standard of care for locally advanced rectal cancer (LARC) has included preoperative chemoradiation, total mesorectal excision surgery and post operative adjuvant chemotherapy based on histopathology. The current therapeutic landscape in LARC has many different options with different directions of travel - depending on the goal of treatment. Enthusiasm for delivering total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is increasing in the light of recently published randomised phase III trials - RAPIDO and PRODIGE-23. There is a wide diversity of different potential schedules and a multitude of approaches, which include induction neoadjuvant chemotherapy (NACT) with a range of chemotherapy options (CAPEOX, FOLFOX, FOLFOXIRI) and a varying duration of 6-18 weeks, or consolidation NACT. These schedules either precede or follow short-course preoperative radiation therapy (SCPRT) using 5 × 5Gy or long-course chemoradiation (LCCRT) using 45-60Gy respectively. The different strategies of induction and consolidation neoadjuvant chemotherapy have been compared and have similar long-term outcomes, but consolidation chemotherapy may facilitate organ-sparing. The results are driving novel paradigms with both intensification and de-intensification treatment strategies. The ideal combination, sequence or duration of such a TNT approach remains undefined. As yet, there are no robust clinical, genetic, molecular, immune or imaging features (alone or integrated), which either direct or aid these choices. Currently, the selection of neoadjuvant treatment is driven by the impact on avoidance or feasibility of surgery or reducing the risk of metastases rather than prevention of local recurrence. Most believe that TNT will improve overall survival, despite the present lack of evidence. Both the inherent heterogeneity in LARC and the observed range of different responses underline the need for response biomarkers to individually tailor therapy rather than 'a one size fits all' approach.
局部进展期直肠癌（LARC）的标准治疗方法包括术前放化疗、全直肠系膜切除术和术后辅助化疗，这些治疗方法基于组织病理学。目前，LARC 的治疗方法有很多种，不同的治疗方法有不同的方向——这取决于治疗的目标。鉴于最近发表的随机 III 期试验——RAPIDO 和 PRODIGE-23，人们对为局部进展期直肠癌（LARC）患者提供全新辅助治疗（TNT）的热情日益高涨。目前有广泛的不同潜在方案和多种方法，包括诱导新辅助化疗（NACT）和一系列化疗方案（CAPEOX、FOLFOX、FOLFOXIRI），以及 6-18 周的不同持续时间，或巩固性 NACT。这些方案要么在短程术前放疗（SCPRT）之前或之后进行，SCPRT 使用 5×5Gy，要么在长程放化疗（LCCRT）之前或之后进行，LCCRT 使用 45-60Gy。诱导和巩固性新辅助化疗的不同策略已经进行了比较，它们具有相似的长期结果，但巩固性化疗可能有助于保留器官。这些结果正在推动新的治疗模式，包括强化和去强化治疗策略。这种 TNT 方法的理想组合、顺序或持续时间仍然没有定义。到目前为止，还没有可靠的临床、遗传、分子、免疫或影像学特征（单独或综合）可以指导或辅助这些选择。目前，新辅助治疗的选择是由手术的可行性或降低转移风险的影响决定的，而不是预防局部复发。尽管目前缺乏证据，但大多数人认为 TNT 将提高总体生存率。LARC 的固有异质性和观察到的不同反应范围强调了需要反应生物标志物来个体化定制治疗，而不是“一刀切”的方法。
