Postsurgical disease recurrence in stage I to III colorectal cancer may be predicted by ctDNA
Findings from a recent study presented at the 2021 Gastrointestinal Cancers Symposium demonstrated that circulating tumour DNA (ctDNA) testing done immediately after surgery enabled clinicians to effectively identify patients with stage I to III colorectal cancer (CRC) who were at high risk for disease recurrence. Long-term, continuous monitoring further increased the predictive power of ctDNA, which was shown to be more reliable than the standard carcinoembryonic antigen (CEA) surveillance or radiological detection.
The study was a collaboration between researchers at the Danish Aarhus University, the INCLIVA Institute in Spain, and the Natera company in the United States, which created the ctDNA detection strategy used in the study.
What is ctDNA?
ctDNA are small pieces of DNA that originate from cancerous cells and tumours. As a tumour grows, cells die and get broken down, releasing their cellular contents (including DNA) into the bloodstream. The amount of ctDNA that is detectable in the blood varies among individuals and will depend on the type of tumour, its location, and the stage of the tumour it comes from.
ctDNA testing, also known as liquid biopsy, can be helpful in detecting and diagnosing a tumour, guiding more tailored, tumour-specific treatment, monitoring the effectiveness of a given treatment, and monitoring cancer recurrence.
In the study, all 260 patients underwent surgery to remove colorectal tumours. Blood plasma samples were collected at various time points (30 days, 3 months, and then every 3 months after surgery for 3 years) for an average time of 29.9 months. After surgery, 80% of patients with detectable ctDNA experienced disease recurrence, as compared to only 13% of patients with undetectable ctDNA.
On average, molecular disease recurrence was identified with ctDNA 8 months before radiologic detection of disease through computed tomography (CT scan). Furthermore, ctDNA outperformed CEA as a biomarker for disease relapse. Long-term CEA assessment failed to reach statistical significance as a prognostic biomarker while long-term ctDNA assessment emerged as a strong, independent one.
As a prognostic biomarker, ctDNA could help to identify the 10-15% of stage I and low-risk stage II patients who are undertreated for their disease, and the approximately 60% of stage II patients who are overtreated. With ctDNA, risk can be identified early and timely intervention can be administered, or treatment can be delayed until patients show evidence of ctDNA negativity. Furthermore, ctDNA testing can help make radiological examination more efficient, which could be intensified in ctDNA-positive patients and eliminated in ctDNA-negative patients, with longitudinal serial ctDNA applied instead.
Take home message:
A recent study has shown that ctDNA is a strong predictive biomarker for colorectal cancer (CRC) recurrence among patients with stage I-III disease. When patients were tested for ctDNA immediately after surgery, ctDNA outperformed carcinoembryonic antigen (CEA) testing or radiologic detection through CT scans in detecting risk of recurrence, especially when it is used in a long-term, continuous fashion.
20 January 2021