Minimal Residual Disease Test Predicts Oligometastatic CRC Patient Outcomes

Colorectal cancer (CRC) is the fourth most common cancer and the second-leading cause of cancer-related death in the USA. Approximately 15%-25% of patients present with metastatic disease upon diagnosis, and approximately 50% of patients with early-stage disease develop metastases.

The current standard of care for CRC involves routine patient checkups, periodic computed tomography scans, and monitoring of carcinoembryonic antigen (CEA) levels. Several studies have indicated the clinical utility of circulating tumor DNA (ctDNA) for Minimal Residual Disease (MRD) assessment, monitoring recurrence, and treatment response in patients with CRC.

Oncologists at the Veneto Institute of Oncology (Padua, Italy) and their associates analyzed a cohort of 112 patients with metastatic CRC (mCRC) who had undergone metastatic resection with curative intent as part of a clinical trial. The study evaluated the prognostic value of ctDNA, correlating MRD status post-surgery with clinical outcomes by using a personalized and tumor-informed ctDNA assay (bespoke multiple PCR, next-generation sequencing assay).

The scientists performed whole-exome sequencing on formalin fixed and paraffin embedded tumor tissue along with matched normal blood samples. On analyzing the sequencing results, a set of 16 patient-specific somatic clonal single nucleotide variants (SNVs) were selected for multiplex PCR (mPCR). The Signatera personalized mPCR next-generation sequencing (NGS) assay (Natera, Austin, TX. USA) was used for detecting minimal or MRD and disease progression in the postsurgical setting for patients with metastatic colorectal cancer. Samples were also prepared for ddPCR (QX200 ddPCR system; Bio-Rad, Berkeley, CA, USA).

Signatera testing identified 61 patients, a little more than half the cohort, as MRD-positive at either the first testing time point after surgery or a second follow-up test. Of these individuals, nearly 97% went on to have progressive disease despite their treatment. To compare Signatera to ddPCR, the group analyzed a subset of 27 patients with KRAS mutations. Concordance between the approaches was only 55%, with the 12 discordant cases representing instances where Signatera was positive and ddPCR was negative. In addition, among these 12 individuals, 11 developed disease progression, suggesting greater sensitivity and accuracy for the personalized Signatera technology. CEA, a highly studied proteomic cancer biomarker, also failed to predict patient outcomes with statistical significance.

Fotios Loupakis, MD, PhD, an Oncologist and first author of the study, said, “Through this study, we are able to show that a personalized ctDNA test is a sensitive prognostic biomarker that can potentially be used to guide treatment decisions for patients with oligometastatic colorectal cancer.”

The authors concluded that their present work supports the continuous expansion of the number of clinical studies in patients with mCRC using personalized ctDNA-based MRD analysis and provides direct evidence of the predictive and prognostic value of ctDNA, which could help clinicians with real numbers to design their clinical studies and support therapeutic decisions in the adjuvant setting. The study was published on July 21, 2021 in the journal JCO Precision Oncology.

Related Links:

Veneto Institute of Oncology
Natera
Bio-Rad