Novel Technology May Better Capture Residual Disease in Colorectal Cancer


Novel, personalized, tumor-informed brPROPHET technology can assess molecular residual disease with greater sensitivity than other assays, according to initial data.

A novel Burning Rock patient-specific prognostic and potential therapeutic marker tracking (brPROPHET) approach proved more sensitive than alternatives when detecting circulating tumor DNA (ctDNA) and thereby identifying molecular residual disease (MRD) in patients with colorectal cancer (CRC) following surgery, according to findings from an initial study presented at the 2023 Gastrointestinal Cancers Symposium.

The brPROPHET approach detected ctDNA in 97.3% of the 74 patients enrolled for all 3 MRD assays, a higher value than investigators achieved with the fixed panel with informed calling (FI) assay (75.7%) and the fixed panel with agnostic calling (FA) assay (68.9%). This novel technology was also the only assay to capture baseline ctDNA in 15 of these patients (20.3%), who had lower median ctDNA levels (0.3 mean tumor molecules [MTM] / mL) than those captured by FI and FA fixed panels (3.0 MTM/mL; P < .05).

Across 135 postoperative blood samples tested by all 3 assays, brPROPHET achieved a positive rate of 14.8%, as compared with 8.1% and 6.7% achieved by the FI and FA fixed panel assays, respectively.

“This method [brPROPHET] was developed to detect MRD with a limit of detection of 0.004% and a sample level specificity of over 99% in the analytical validation,” presenting author Di Cao, MD, a physician at Sun Yat-sen University Cancer Center in Guangzhou, China, said during the presentation. “[Our] study reported that the clinical validation of the brPROPHET assay in colorectal cancer demonstrated superior sensitivity in detecting preoperative and post-operative ctDNA [vs] fixed-panel assays.”

The brPROPHET assay is designed to trace patient-specific somatic variants based on whole-exome sequencing of the tumor tissue and matched white blood cells. It targets up to 55 variants per patient.

The study investigators evaluated assay sensitivities in a population of 117 patients, including 53 (45.0%) with stage II CRC and 41 (35.0%) with stage III. They performed FI and FA fixed panel assays in a subset of patients with a 168-gene panel spanning 273 kilobases of the human genome for comparison with brPROPHET. Sixty (51.0%) patients received adjuvant therapy after surgery.

“Of the designed variants for ctDNA detection, only 6%...were included in the fixed panel. Seventy-five percent of genes selected for panel design were private to a specific patient, suggesting the broadness of MRD detection,” Cao said.

The median patient age of the population was 57 years. Most enrolled patients were male (55.5%), and a plurality had left-sided disease (42.7%) rather than right-sided (26.5%), rectal (23.9%), or transverse (6.8%) disease.

Preoperative ctDNA was detected in 97% of patients (n = 113) overall; much higher detection rates occurred in patients with later stage vs stage I disease. Additionally, median ctDNA levels were higher in patients with later stage disease and correlated with tumor volume.

The overall positivity rate declined to 18% on day 7 following surgery and 15% on day 30.

Two patients relapsed during the short follow-up period; ctDNA was detected prior to radiological relapse in both, with a lead time of 1 and 2 months, respectively.

“Identifying MRD with tailored, tumor-informed, ctDNA-based next-generation sequencing (NGS) assays after curative surgery could facilitate the individualized management of [patients with] resected CRC,” the investigators concluded. “Longitudinal monitoring is ongoing for further analysis of clinical outcomes and serial tests.”


Cao D, Wang F, Zhang R, et al. Patient-specific tumor-informed circulating tumor DNA (ctDNA) analysis for molecular residual disease (MRD) detection in surgical patients with stage I-IV colorectal cancer (CRC). J Clin Oncol. 2023;41(suppl 4):213. doi:10.1200/JCO.2023.41.3_suppl.213

Related Videos
Arvind N. Dasari, MD, MS, an expert on colorectal cancer
A panel of 5 experts on colorectal cancer
Considering cystectomy in patients with bladder cancer may help with managing the shortage of Bacillus Calmette-Guerin, according to Joshua J. Meeks, MD, PhD, BS.
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Patients with locally advanced or metastatic urothelial cancer and visceral disease may particularly benefit from enfortumab vedotin plus pembrolizumab, according to Amanda Nizam, MD.
High-grade adverse effects with zanidatamab plus palbociclib and fulvestrant seem to be uncommon in patients with HER2-positive, hormone receptor–positive, metastatic breast cancer, according to Sara Hurvitz, MD, FACP.
Black male patients with breast cancer appear to experience worse survival outcomes compared with White patients when controlling for clinicopathological variables, according to Jason (Jincong) Q. Freeman, MPH, MS.
Results from the ECOG-ACRIN E4112 trial appear to support the use of DCIS scores for identifying patients with breast cancer who may be eligible to omit radiotherapy following MRI-guided surgery.
Providers should inform patients with breast cancer that selecting later-line therapies following prior treatment with CDK4/6 inhibitors is a “developing area,” says Abigail M. Johnston, JD.
Data from the phase 3 NATALEE trial highlight a positive toxicity profile for ribociclib as an adjuvant therapy for patients with hormone receptor–positive, HER2-negative breast cancer, says Neil M. Iyengar, MD.
Related Content