Airoldi Marco, Roselló Susana, Tarazona Noelia, Huerta Marisol, Pérez-Santiago Leticia, Fleitas Tania, Pla-Martí Vicente, Puccini Alberto, Roda Desamparados, Cervantes Andrés
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy; Department of Medical Oncology, Hospital Clínico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.
Department of Medical Oncology, Hospital Clínico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; Instituto de Salud Carlos III, CIBERONC, Madrid, Spain.
Cancer Treat Rev. 2025 Nov;140:103015. doi: 10.1016/j.ctrv.2025.103015. Epub 2025 Aug 19.
The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy's potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient's well-being.
近年来，局部晚期直肠癌（LARC）的治疗发生了重大变革，正朝着更具选择性的策略发展，这些策略在肿瘤学疗效与生活质量（QoL）保留之间取得平衡。全新辅助治疗（TNT）改善了局部控制并减少了远处转移，但其长期毒性引发了人们对治疗降阶梯策略的日益关注，这些策略旨在在保持疗效的同时尽量减少不良反应。本综述聚焦于LARC的治疗进展，分析既定标准和新兴创新。我们讨论了器官保留方法的日益采用，特别是针对达到临床完全缓解（cCR）的患者的观察等待（WW）策略，以及在明确病例中可能选择性省略放疗。此外，我们探索并研究了在不影响治愈率的情况下保留功能的侵入性较小的手术技术。除了标准治疗方法，我们强调免疫疗法的作用，特别是其在错配修复缺陷/微卫星不稳定（dMMR/MSI）的LARC中的突破性疗效，从而引出了免疫消融的概念：在使患者免受化疗、放疗和手术的同时实现肿瘤完全消退。正在进行的研究也在调查免疫疗法在错配修复功能正常/微卫星稳定（pMMR/MSS）的LARC中的潜在作用。最后，我们讨论新兴的预测生物标志物，如循环肿瘤DNA（ctDNA）和放射组学，它们可能会优化患者选择并指导治疗个体化。LARC管理的未来在于精准驱动的方法，即在不影响QoL的情况下优化生存率。通过拥抱创新和个性化护理，我们正在进入一个新的时代，在这个时代，治愈仍然至关重要，但绝不能以牺牲患者的福祉为代价。
