ctDNA predicts colorectal cancer survival

By Kayla Lee

A systematic review and meta-analysis published in Cancer Treatment Reviews indicates that rising circulating tumor DNA (ctDNA) levels are a strong prognostic marker for disease progression and cancer-related mortality.

The study authors say this demonstrates the potential for ctDNA measurement to distinguish patients who will benefit from continued treatment from those who need an alternative option – even before radiologic imaging.

Anja Holz (University Medical Center Hamburg-Eppendorf, Germany) and colleagues conducted the review to evaluate the prognostic value of sequential ctDNA measurements via liquid biopsy in people with metastatic colorectal cancer (mCRC) receiving systemic therapy. They included 103 studies in the systematic review and 56 of these, involving 6,099 patients (3,735 evaluable), in the meta-analysis.

Rising ctDNA levels during systemic therapy were significantly associated with poorer outcomes, including progression-free survival (HR=2.44), overall survival (HR=2.53), and recurrence-free survival (HR=6.18). Additionally, patients with increasing ctDNA had a higher risk of disease progression (RR=4.58) and were more likely to show non-response to therapy (OR=2.33).

Based on 648 patient-level assessments across six studies, ctDNA testing showed strong diagnostic performance, with sensitivity ranging from 70% to 94% and specificity from 72% to 99%. Pooled estimates indicated 80% sensitivity, a 7% false positive rate, and an area under the receiver operating characteristic curve of 0.83, reflecting high overall accuracy.

Holz and colleagues identified inconsistent reporting of common confounding factors as a major weakness in their review.

The researchers conclude that “we recommend longitudinal ctDNA measurements to be included in clinical mCRC intervention trials to evaluate the role of ctDNA guided therapy decision making, such as performed for stage II colorectal cancer. The results of these studies will provide the basis to consider inclusion of ctDNA dynamics in the RECIST criteria.”

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