Liquid biopsy identifies need for adjuvant therapy in stage II colon cancer

June 6, 2022

In patients with stage II colon cancer, for which cancer DNA was not present in the blood (circulating tumor DNA, or ctDNA) post-surgical chemotherapy could be skipped without compromising recurrence-free survival. Conversely, for patients where ctDNA was present after surgery, the rate of recurrence among those who received chemotherapy was low, suggesting a survival benefit from post-surgical chemotherapy, according to a news release.

455 patients with curatively resected stage II colon cancer in Australia and New Zealand, including some patients with rectal cancer.

Fewer patients in the ctDNA-guided group received post-surgical chemotherapy vs. standard management (15.3% vs 27.9%, respectively). Standard management was based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.

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 positive ctDNA result, who received post-surgical chemotherapy, had a three-year recurrence-free survival rate of 86%.

The results of this study should help guide the use of post-surgical chemotherapy in patients with stage II colon cancer.

Key Findings:

While the current standard of care for stage II colorectal cancer does not involve a ctDNA-directed approach to post-surgical chemotherapy, the randomized phase II DYNAMIC trial results demonstrated similar recurrence-free survival between a ctDNA-guided arm and a standard management arm, despite fewer patients receiving post-surgical chemotherapy.

In the ctDNA-guided arm, patients with a positive ctDNA test result were treated with adjuvant chemotherapy while those with negative results were not, almost halving the total number of patients who needed to be treated with post-surgical chemotherapy compared to standard management (15.3% vs. 27.9%). 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 tumors that had grown into the outer lining of the bowel wall but had not grown through it (5.8%).

Patients with a positive ctDNA result, who received post-surgical chemotherapy, had a three-year recurrence-free survival rate of 86%. Guidance with ctDNA assessment was comparable to standard management for two-year recurrence-free survival (93.5% vs. 92.4%, respectively) and three-year recurrence-free survival (91.7% vs. 92.4%, respectively). 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.

“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. Our findings show that with adjuvant treatment, ctDNA-positive patients derive considerable benefit from chemotherapy such as an oxaliplatin-based regimen,” said lead author Jeanne Tie, MD, an Associate Professor at the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Center, Victoria, Australia.

About 151,030 new colorectal cancer cases are expected to be diagnosed in the United States (U.S.) in 2022. An estimated 52,580 deaths will occur due to the disease.

Circulating tumor DNA can detect micro-metastatic disease (also referred to as minimal residual disease) after surgery, allowing for a more precise prediction of recurrence risk and patient selection for post-surgical therapy. This is the first study to use ctDNA to direct post-surgical therapy in colon cancer.

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