Predicting recurrence in CRC using post-operative circulating tumour DNA
Circulating tumour DNA (ctDNA) refers to the fragments of genetic material (DNA) from tumours that can be detected in the blood. A ctDNA negative result means that no remaining cancer was detected by the test. While this does not guarantee that the cancer will not come back, studies show that patients who are ctDNA negative after the end of treatment have a lower chance of experiencing a cancer recurrence. A ctDNA positive result means that fragments of tumour DNA were detected in the blood, indicating the presence of residual or remaining cancer cells. Studies show that patients who receive a ctDNA positive result are more likely to experience a cancer recurrence.
A recent update from the GALAXY study presented at the 2023 ASCO Breakthrough meeting found that post-operative (after surgery) molecular residual disease detected by ctDNA at 4 weeks after surgery was the strongest prognostic risk factor for disease-free survival in patients with colorectal cancer who had undergone surgery.
Molecular residual disease: the presence of tumour-specific genetic material (DNA) in the body after cancer treatment.
Prognostic risk factor: factors that provide information regarding the patient’s outcomes.
Disease-free survival: the amount of time after treatment during which no sign of cancer is found.
This finding was found to be relevant regardless of the tumour’s BRAFV600E and microsatellite-instability high (MSI-H) status. Both BRAF and MSI-H status were determined to be important prognostic factors in disease-free survival, and adding ctDNA status enhanced the ability to estimate the risk of recurrence; These findings are important as they can help to inform selection of the most appropriate therapies after surgery for these patients.
About ctDNA analysis
ctDNA is currently being studied as a non-invasive tool (i.e. can be examined through a blood test as opposed to a more invasive biopsy) to detect molecular residual disease and measure the effectiveness of therapies for patients with colorectal cancer.
In the phase III CIRCULATE-Japan initiative, the clinical usefulness of ctDNA analysis was evaluated so that the most appropriate follow-up therapy (adjuvant therapy) after surgery could be selected. The GALAXY study is the first of the trials included in CIRCULATE-Japan, and it is a large-scale nationwide registry that monitors ctDNA in patients with stage II-IV colorectal cancer eligible for surgery. In GALAXY, ctDNA is analyzed at various timepoints following surgery, with the earliest assessment done at 4 weeks post-surgery. Further ctDNA assessments are done at 3, 6, 9, 12, 18, and 24 months after surgery until cancer recurrence. CT scans are also done every 6 months.
From the GALAXY analysis, BRAF and MSI status were both determined to be statistically significant prognostic markers for cancer recurrence. However, receiving a positive ctDNA result was found to be the strongest prognostic factor for cancer recurrence. It was significantly associated with shorter disease-free survival and was the most significant compared to the other factors.
The GALAXY researchers plan to validate their findings in a larger patient population in the future. From the GALAXY findings, two phase III trials are currently investigating ctDNA-guided adjuvant therapy.