Researchers found that post-chemotherapy minimal residual disease (MRD) subtypes were associated with a pattern of failure and time to failure.
With 1 in 4 patients with stage 3 colon cancer relapsing within 5 years as a result of minimal residual disease (MRD) not eliminated by surgery and chemotherapy, researchers analyzed different subtypes of MRD and their impact on relapse. What they found was that post-chemotherapy MRD subtypes were associated with a pattern of failure and time to failure.
The 76 patients included in the study received testing for circulating tumor cells (CTCs) and bone marrow micrometastasis 1 month after curative surgery and again 1 month after completing FOLFOX chemotherapy. Based on results from blood and bone marrow samples, they were defined as either negative for both CTC and micrometastasis, positive for micrometastasis only, or positive for CTC only.
Patients were followed for up to 5 years, during which 31 (41%) relapsed.
After surgery but before receiving chemotherapy, 21 (28%) patients were negative for both CTC and micrometastasis, 21 (28%) were positive for micrometastasis, and 34 (44%) were positive for CTC. However, response to chemotherapy was heterogenous and the subtype of MRD did not predict response.
Following chemotherapy, 38 (50%) patients were CTC- and micrometastasis-negative, 17 (22%) were micrometastasis-positive, and 21 (28%) were CTC-positive. At 3 years, overall survival was 64%, which fell to 58% after 5 years.
While patients who were negative for both measures and patients who were positive for micrometastasis did not reach the median relapse-free survival, patients who tested positive for CTCs had a median relapse-free survival of just over 1 year.
“The results of the study suggest that that presence of minimal residual disease after chemotherapy has clinically important consequences,” wrote the researchers.
At 3 years, 92% of patients who were negative for both measures were still alive, as were 71% of patients who were micrometastasis-positive. Meanwhile, just 6% of patients who were CTC-positive remained alive.
By the end of the 5 years, 88% of those who were CTC- and micrometastasis-negative and 62% of those who were micrometastasis-positive were still alive, compared with 4% of those who were CTC-positive.
“Patients negative for CTCs but positive for micro-metastasis had a similar outcome to MRD negative patients for the first 18 months post-chemotherapy,” explained the researchers, who added that, after 18 months, there was in increasing relapse rate, suggesting that these patients are at risk of late relapse.
Due to the small number of patients included in the study, the conclusions are limited, noted the researchers, and thus larger multicenter studies are warranted.
Murray N, Aedo S, Villalon R, et al. Effect of FOLFOX on minimal residual disease in stage III colon cancer and risk of relapse [published online June 27, 2019]. Ecancermedicalscience. doi:10.3332/ecancer.2019.935.