Liquid Biopsy Predicts Colon Cancer Relapse Months Earlier

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue.

Despite improvements in curative-intent treatment for stages I-III CRC, 20%-30% of patients relapse. Better detection of minimal residual disease (MRD) could improve postoperative risk assessment, and earlier detection of recurrence would allow more patients to receive curative-intent therapy after recurrence and lead to better survival.

Medical scientists at the Aarhus University (Aarhus, Denmark) organized a clinical study to test the hypothesis that postoperative circulating tumor DNA (ctDNA) measurement could identify patients with MRD and stratify patients into high- and low-risk groups. They also wanted to assess post-treatment relapse risk in ctDNA-positive patients and determine the lead time from ctDNA detection to radiographic recurrence. Data analysis included 260 patients with stages I-III CRC, 48 of who relapsed after curative-intent treatment. The cohort consisted of four patients with stage I disease, 90 with stage II, and 166 with stage III. There were 165 patients who received adjuvant therapy, and relapse-free patients had a median follow-up of 29.9 months.

Assessment of ctDNA was performed in 218 patients with the Signatera assay (Natera, San Carlos, CA, USA), which identified 20 patients with detectable ctDNA (MRD positive) and 198 with no detectable ctDNA. A positive ctDNA test was associated with a recurrence hazard ratio (HR) of 11.0. Among patients who received adjuvant chemotherapy, a positive ctDNA test at the end of treatment was associated with a recurrence rate of 83.3% as compared with 12.5% for those who had negative ctDNA tests (HR 12). Longitudinal assessment of ctDNA showed that the risk of recurrence increased over time in ctDNA-positive patients and decreased in ctDNA-negative patients (89.3% versus 3.4%, HR 51).

The investigators compared the performance of ctDNA with the tumor-associated protein CEA. Measurement of postoperative CEA (n=175) and after adjuvant chemotherapy (n=99) did not have a significant association with the risk of recurrence. Longitudinal assessment of CEA (n=197) did predict an increased risk of recurrence (HR 4.9), but not as well as longitudinal ctDNA (n=197, HR 95.7). In a subgroup of 29 patients with clinical recurrence detected by CT scan, ctDNA detection ensured a median of 8.1 months earlier.

Tenna V. Henriksen, PhD, the first author of study, said, “We saw that patients with ctDNA detected immediately after surgery had a very high risk of recurrence. We also saw that longitudinal monitoring increased the predictive power of ctDNA. Molecular recurrence by ctDNA was detected a median of eight months before radiological detection of recurrence. Using longitudinal testing with ctDNA outperforms CEA in recurrence-free survival prediction.”

The authors concluded that postoperative ctDNA positive status was associated with markedly reduced relapse-free survival (RFS) compared to CEA. The study also shows that effective therapy can be curative in a portion of MRD-positive patients. In a longitudinal setting, ctDNA analysis predicted the risk of recurrence and is a more reliable biomarker for treatment response monitoring. The study was presented at the Gastrointestinal Cancers Symposium virtual meeting held January 15-17, 2021.

Related Links:
Aarhus University
Natera