Interim results from the VICTORI study showed that an ultrasensitive circulating tumor DNA (ctDNA)-based liquid biopsy assay was effective in detecting signs of cancer recurrence prior to imaging and provided prognostic value within 1 month after surgery in patients with colorectal cancer. The study, conducted by Titmuss et al, was presented during the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago (Abstract 3774).

The use of ctDNA for the detection of measurable residual disease (MRD) after treatment in patients with colorectal cancer is prognostic. However, not all cancers are detected prior to clinical recurrence, potentially because of the effects of chemotherapy and surgery on the presence of ctDNA, among other factors.

Study Methodology

The goal of this study was to determine the optimal timepoint at which detecting ctDNA can predict recurrence after surgery in patients with colorectal cancer. The interim prospective analysis included 71 patients with resectable colorectal cancer. A total of 52 patients had stage I to III disease, and 19 had stage IV cancer.

The researchers built a personalized, tumor tissue–derived panel of up to 1,800 somatic variants for each patient for MRD detection, enabling detection of ctDNA down to ~1 part per million. Liquid biopsies were taken prior to surgery, within the MRD landmark window (weeks 2, 4, 6, and 8), and on follow-up thereafter every 3 months for 3 years. The results were analyzed with the NeXT Personal^® assay.

Key Results

The researchers found that all 33 patients with treatment-naive disease greater than stage I had detectable ctDNA prior to surgery. Of the 65 patients evaluable for clinical outcome, 23 experienced clinical recurrence, the vast majority (87%) had ctDNA-positive disease within the landmark 8-week postoperative period during which adjuvant chemotherapy is typically administered. All of the patients with clinical recurrence were ctDNA-positive before recurrence was detected via reflex imaging, by a median of 198 days earlier, including difficult-to-detect metastatic sites, such as the lungs.

One patient had ctDNA recurrence 416 days prior to clinical recurrence. According to the researchers, ctDNA was detected as low as 2 parts per million. The median ctDNA level at first detection was 24.4 parts per million, and the highest was 111,120 parts per million. Higher ctDNA levels at first detection were linked to shorter times to clinical relapse.

“The VICTORI study is an ongoing study to understand the prognostic value of ultrasensitive ctDNA detection and determine the optimal timepoint for detecting MRD postsurgery. Preliminary results indicate NeXT Personal detects MRD at ultralow levels and is prognostic as early as 2 weeks postsurgery for recurrences,” concluded the study authors.

Disclosure: The study was funded by Personalis and BC Cancer Foundation. For full disclosures of the study authors, visit aacr.org.