A/Prof Jeanne Tie

Australian research shows that liquid biopsy may be a useful tool for identifying which patients with stage II colon cancer will benefit from further treatment and allow about half to safely avoid unnecessary adjuvant chemotherapy.

Associate Professor Jeanne Tie and colleagues at the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Centre, Victoria, presented data at ASCO 2022 showing that use of circulating tumour DNA (ctDNA) to assess minimal residual disease could guide decisions on whether post-surgical chemotherapy may be skipped without compromising recurrence-free survival.

In a study involving 455 patients with curatively resected stage II colon cancer in Australia and New Zealand, they compared outcomes for patients who were randomly assigned to have treatment decisions guided by either ctDNA results or standard clinicopathological features.

Patients with a ctDNA-positive result after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy, while patients who were ctDNA-negative were not treated

The results showed that fewer patients in the ctDNA-guided group received post-surgical chemotherapy compared to those who had standard management (15% vs 28%, respectively).

Despite the differences in post-surgical therapy, the recurrence-free survival rates at two years were  non-inferior for  ctDNA-guided management compared to standard management (93.5% and 92.4%, respectively).

According to the findings, published simultaneously in the NEJM, three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.

Without post-surgical chemotherapy, the three-year recurrence-free survival for ctDNA-negative patients was 96.7% in the low-risk group and 85.1% in the high-risk group.

Of those who received post-surgical chemotherapy, oxaliplatin was given more frequently than fluoropyrimidine for ctDNA-guided patients compared to standard management patients (62.2% vs. 9.8%).

Patients with a negative ctDNA result, who did not receive post-surgical chemotherapy, had a very low risk of recurrence (7.5%); the risk was even lower in negative ctDNA patients without any clinical risk features (3.3%) or among those negative ctDNA patients with tumours that had grown into the outer lining of the bowel wall but had not grown through it (5.8%).

“The DYNAMIC study results are very encouraging because previous data suggest that patients with a positive ctDNA score after surgery have a very high recurrence risk if no further treatment is given.  Said Associate Professor Tie.

“Our findings show that with adjuvant treatment, ctDNA-positive patients derive considerable benefit from chemotherapy such as an oxaliplatin-based regimen,” she added.

An accompanying commentary in NEJM said the investigators had shown that liquid biopsy could be “a very important step toward improving precision oncologic treatment for patients with colon cancer.”

However the authors noted there were still unanswered question such as whether selected patients with high-risk pathological factors and ctDNA-negative disease might benefit from chemotherapy.

“[And] because ctDNA positivity appears to define molecular persistence of disease … more follow-up is needed to determine whether chemotherapy prevents or just delays relapse,” they wrote.

“Further studies integrating assessments of minimal residual disease with standard factors or new biologic markers may help to further increase precision in this context,” they concluded.