Holz Anja, Paul Bidisha, Zapf Antonia, Pantel Klaus, Joosse Simon A
Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cancer Treat Rev. 2025 Sep;139:102999. doi: 10.1016/j.ctrv.2025.102999. Epub 2025 Jul 24.
The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy.
Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included.
Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02-2.95) and overall survival (HR: 2.53, 95% CI: 2.01-3.18), which were reported in 39 and 33 studies, respectively.
Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions.
The protocol for this review was registered on PROSPERO (CRD42023420012).
目前通过放射影像学评估转移性结直肠癌（mCRC）的全身治疗反应。然而，越来越多的研究表明，作为液体活检的循环肿瘤DNA（ctDNA）可用作评估治疗疗效的替代方法。我们进行了一项系统评价，并对主要研究进行了荟萃分析，以评估序贯液体活检在接受全身治疗的转移性结直肠癌患者中的预后价值。
纳入随机、非随机和前瞻性观察性研究，这些研究报告了在接受转移性结直肠癌治疗的患者全身治疗过程中，总游离DNA中ctDNA浓度的变化，以根据RECIST标准预测治疗反应。
荟萃分析纳入了56项研究，涉及3735例可评估的转移性结直肠癌患者。与基线相比，全身治疗期间ctDNA增加与无进展生存期（HR：2.44，95%CI：2.02-2.95）和总生存期（HR：2.53，95%CI：2.01-3.18）密切相关，分别在39项和33项研究中报告。
我们的分析强调了通过液体活检对mCRC患者进行基于血浆的纵向ctDNA分析具有很强的预后价值。后续研究应评估ctDNA在指导治疗决策中的作用，特别是在确定可能从继续或改变全身治疗中获益的患者方面。虽然ctDNA检测的进一步标准化仍然必要，但目前的证据支持将连续ctDNA监测纳入即将开展的临床mCRC干预试验，为将其纳入未来的RECIST版本奠定基础。
本综述的方案已在PROSPERO（CRD42023420012）上注册。
