Study Shows ctDNA Liquid Biopsy Detects Colorectal Cancer Recurrence Earlier Than Imaging

Interim results from the VICTORI study, presented at the ongoing American Association for Cancer Research (AACR) Annual Meeting 2025 (April 25–30), show that an ultrasensitive liquid biopsy assay based on circulating tumor DNA (ctDNA) can detect signs of recurrence. Developed by Personalis, Inc. in collaboration with BC Cancer, the assay can detect molecular residual disease (MRD) and predict recurrence in colorectal cancer (CRC) patients earlier than conventional imaging.

VICTORI Study Analyzes ctDNA in 71 Colorectal Cancer Patients Using 1,800 Somatic Variants and NeXT Personal Assay

The VICTORI study, presented, evaluated the optimal timepoint for detecting ctDNA to predict recurrence after surgery in colorectal cancer (CRC) patients. This interim analysis included 71 patients with resectable CRC, comprising 52 patients with stage 1–3 disease and 19 with stage 4 disease. Researchers created a personalized, tumor tissue-derived panel of up to 1,800 somatic variants for each patient. Researchers collected liquid biopsies before surgery, every two weeks for eight weeks after surgery, and every three months for up to three years. They analyzed the samples using the NeXT Personal assay.

All 33 patients with treatment-naïve disease greater than stage 1 had detectable ctDNA prior to surgery. Among 65 patients evaluable for clinical outcomes, 23 experienced clinical recurrence. Of these, 87% tested ctDNA-positive within the eight-week post-surgical period, a timeframe when adjuvant chemotherapy typically occurs.

“After surgery, ctDNA-based liquid biopsies may help identify patients who would benefit most from additional treatment,” said Jonathan Loree, MD, MS, a medical oncologist at BC Cancer and the senior investigator of the study. “Alternatively, this may help patients with good prognosis avoid toxicities from unnecessary chemotherapy. By monitoring patients for recurrences, liquid biopsies can continue to support clinical care and allow more patients to undergo second curative intent surgeries to remove early recurrences.”

ctDNA Detection Precedes Clinical Recurrence by 198 Days in Colorectal Cancer, With Levels as Low as 2 ppm 

The study found that ctDNA detection preceded clinical recurrence identified by imaging by a median of 198 days, including in difficult-to-detect metastatic sites such as the lung. In one case, the study detected ctDNA recurrence 416 days before clinical relapse. Study presenter Emma Titmuss, MSc, a bioinformatician at BC Cancer in Vancouver, reported detecting ctDNA at levels as low as 2 parts per million (ppm). The median ctDNA level at first detection was 24.4 ppm, with the highest recorded at 111,120 ppm. Higher ctDNA levels at first detection associate with shorter times to clinical relapse.

Titmuss noted that although ctDNA detection after treatment is a strong indicator of recurrence in CRC, very low ctDNA levels often make detection challenging. Early identification of ctDNA, she explained, could provide actionable information to guide clinical decision-making.

The study is ongoing, enrolling additional patients to enhance result precision and inform future prospective studies incorporating ctDNA as a key decision point in clinical management and care. As stated by the presenter, a limitation of the study is the lack of intervention following ctDNA detection, as it was observational. The researchers emphasize the need for randomized trials to assess the most effective use of this technology in clinical practice.

“The results from our study help to clarify the ideal timepoint for ctDNA testing following a surgical procedure, showing that we can detect residual cancer as early as two weeks following surgery,” said Titmuss.

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Denisse Sandoval