Liquid biopsy for colorectal cancer could guide therapy for tumours

A study published in the Journal of Clinical Oncology Precision Oncology showed that liquid biopsy testing using blood or urine samples can help to determine the most appropriate treatment for colorectal cancer (CRC) in the early stages of metastasis. By detecting the presence or absence of residual cancer cells, liquid biopsy can help to guide treatment decisions.

What is liquid biopsy?

Liquid biopsy is a test that detects the presence of genetic material from tumours, known as circulating tumour DNA (ctDNA), that is released by tumours cells into the circulation. It is detectable in the blood, and to a less extent, in urine. A liquid biopsy may be used to:

• Help detect cancer at an early stage;
• Help plan treatment;
• Discover how well a treatment is working;
• Discover whether the cancer has come back.

Liquid biopsy usually only requires a simple blood test, compared to tissue biopsy which requires surgical removal of tissue for examination. When liquid biopsy is performed repeatedly in the same patient over time, the results can help clinicians better understand what type of molecular changes are taking place in a tumour. This allows for a more personalized treatment approach that minimizes side effects and can help to improve patient outcomes.

The Study

Patients included in the study had oligometastatic CRC, indicating that their cancer had spread to small number of sites beyond the original tumour. The current standard of care includes pre-operative chemotherapy to shrink the tumours before having surgery to remove any visible remaining tumours. After surgery, there is disagreement across oncology centres as to what type of treatment should follow. Some clinicians believe that these patients should be treated as if they had generalized metastatic disease, therefore following surgery with more chemotherapy, while other clinicians believe that oligometastatic CRC should be treated like localized cancer, with further surgery and radiation at the few sites of metastases. A major difficulty lies in the limited ability to evaluate how patients respond to initial chemotherapy.

With liquid biopsy testing, patients’ response to early chemotherapy can be measured. If the liquid biopsy detects very low levels of ctDNA, suggesting that the patient responded well to initial chemotherapy, they may follow a less intensive treatment regimen indicated for patients with localized disease. Alternatively, if the liquid biopsy detects elevated levels of ctDNA, suggesting that the patient did not respond well to initial therapy, it may be recommended that they receive more intensive chemotherapy and follow a treatment regimen indicated for patients with metastatic disease.

In the study, patients who had lower levels of ctDNA in the blood correlated with better response rates to early chemotherapy. Most patients who had very low levels of ctDNA in the blood also showed no measurable cancer in their surgically removed tumour tissue. ctDNA analysis was found to be highly sensitive and specific (95% and 100%, respectively) in detecting minimal residual disease (remaining cancer cells) after initial chemotherapy. While urine-based ctDNA testing was feasible, it was found to be less sensitive than using a blood sample. Furthermore, ctDNA anaylsis revealed that 81% of patients may have been candidates for post-operative immunotherapy, based on high tumor mutational burden, or targeted therapy, based on the presence of PIK3CA mutations. Liquid biopsy presents itself as a promising tool in detecting minimal residual disease and guiding personalized treatment decisions for patients with oligometastatic CRC.

Take away message:

Liquid biopsy, a test that examines the levels of circulating tumour DNA in the blood or urine, can be used to detect residual cancer cells after initial treatment with chemotherapy and surgery. Based on each patient’s unique findings, clinicians can follow distinct treatment pathways that are tailored to each individual’s disease.