Martínez-Castedo B, Camblor D G, Martín-Arana J, Carbonell-Asins J A, García-Micó B, Gambardella V, Huerta M, Roselló S, Roda D, Gimeno-Valiente F, Cervantes A, Tarazona N
Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; CIBERONC, Carlos III Health Institute, Madrid, Spain.
Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.
Ann Oncol. 2025 Mar;36(3):263-276. doi: 10.1016/j.annonc.2024.12.006. Epub 2024 Dec 13.
Circulating tumor DNA (ctDNA) analysis has emerged as a minimally invasive tool for detecting minimal residual disease (MRD) in colorectal cancer (CRC) patients. This enables dynamic risk stratification, earlier recurrence detection and optimized post-surgical treatment. Two primary methodologies have been developed for ctDNA-based MRD detection: tumor-informed strategies, which identify tumor-specific mutations through initial tissue sequencing to guide ctDNA monitoring, and tumor-agnostic approaches, which utilize predefined panels to detect common cancer-associated genomic or epigenomic alterations directly from plasma without prior tissue analysis. The debate over which is superior in terms of sensitivity, specificity, cost-effectiveness and clinical feasibility remains unsolved.
This review summarizes studies published up to November 2024, exploring the utility and performance of tumor-informed and tumor-agnostic approaches for ctDNA analysis in CRC. We evaluate the strengths and limitations of each methodology, focusing on sensitivity, specificity and clinical outcomes.
Both strategies demonstrate clinical utility in post-operative risk stratification and guiding adjuvant chemotherapy decisions in CRC patients. Tumor-informed approaches generally exhibit superior sensitivity and specificity for recurrence prediction, attributed to their personalized tumor profile designs. However, these methods are limited by the need for prior tissue sequencing and higher associated costs. In contrast, tumor-agnostic approaches offer broader applicability due to their reliance on plasma-only analysis, although with relatively lower sensitivity. Technological advancements, including fragmentomics and multi-omic integrations, are expanding the capabilities of ctDNA-based MRD detection, enhancing the performance of both approaches.
While tumor-informed strategies currently offer higher precision in MRD detection, tumor-agnostic approaches are gaining traction due to their convenience and improving performance metrics. The integration of novel technologies in ongoing clinical trials may redefine the optimal approach for MRD detection in CRC, paving the way for more personalized and adaptive patient management strategies.
循环肿瘤DNA（ctDNA）分析已成为检测结直肠癌（CRC）患者微小残留病（MRD）的一种微创工具。这有助于进行动态风险分层、更早地检测复发以及优化术后治疗。基于ctDNA的MRD检测已开发出两种主要方法：肿瘤知情策略，即通过初始组织测序识别肿瘤特异性突变以指导ctDNA监测；以及肿瘤非依赖方法，即利用预定义的检测板直接从血浆中检测常见的癌症相关基因组或表观基因组改变，而无需事先进行组织分析。关于哪种方法在敏感性、特异性、成本效益和临床可行性方面更具优势的争论仍未解决。
本综述总结了截至2024年11月发表的研究，探讨了肿瘤知情和肿瘤非依赖方法在CRC的ctDNA分析中的实用性和性能。我们评估了每种方法的优势和局限性，重点关注敏感性、特异性和临床结果。
两种策略在CRC患者的术后风险分层和指导辅助化疗决策方面均显示出临床实用性。肿瘤知情方法通常在复发预测方面表现出更高的敏感性和特异性，这归因于其个性化的肿瘤特征设计。然而，这些方法受到需要事先进行组织测序以及相关成本较高的限制。相比之下，肿瘤非依赖方法由于仅依赖血浆分析而具有更广泛的适用性，尽管其敏感性相对较低。包括片段组学和多组学整合在内的技术进步正在扩展基于ctDNA的MRD检测能力，提高了两种方法的性能。
虽然目前肿瘤知情策略在MRD检测中提供了更高的精度，但肿瘤非依赖方法因其便利性和不断改善的性能指标而越来越受到关注。正在进行的临床试验中新技术的整合可能会重新定义CRC中MRD检测的最佳方法，为更个性化和适应性更强的患者管理策略铺平道路。
