Post-Treatment ctDNA Linked To Stage III Colon Cancer Prognosis

medwireNews: Detection of circulating tumour (ct)DNA after surgery or adjuvant chemotherapy is linked to a poor prognosis for patients with stage III colon cancer, say researchers who believe these high-risk patients are candidates for further treatment.

“Our study highlights the potential clinical utility of ctDNA to guide therapeutic decision-making”, write Jeanne Tie, from Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and co-authors in JAMA Oncology.

They say their findings both “confirm the prognostic significance of postsurgical ctDNA analysis, which has now been demonstrated in multiple series of colorectal cancer and other solid tumors” and “suggest that postchemotherapy ctDNA analysis could lead to a more informed selection of patients who could benefit from additional therapeutic approaches, supporting the pursuit of clinical trials of novel agents in this high-risk population.” 

Plasma samples were taken from 96 patients attending five Australian hospitals with newly diagnosed stage III colon cancer between 2014 and 2017.The cohort was followed up for a median of 28.9 months, during which time 25% of patients experienced recurrence, including 21% of those who received at least 12 or 24 weeks of adjuvant chemotherapy, and the one patient who did not receive chemotherapy.

A fifth (21%) of the patients had ctDNA detected in blood samples collected a median of 42 days after surgery and this was a significant predictor for future disease, with a hazard ratio (HR) of 3.8 for recurrence.

Patients with postoperative ctDNA were significantly less likely to be free from recurrence at 3 years, at 47% versus 76% for their ctDNA-negative counterparts.

And multivariate analysis indicated that a positive postoperative ctDNA status was the strongest independent predictive factor for recurrence, with a HR of 7.5, followed by a high clinical risk (pT4 or pN2 disease; HR=2.5).

In addition, 17% of 88 patients with blood samples taken after adjuvant chemotherapy tested positive for ctDNA and these individuals were significantly less likely to achieve a 3-year recurrence-free interval, at 30% versus 77% of those without ctDNA (HR=6.8).

The researchers hypothesise that “[t]he treatment of patients with detectable ctDNA levels but without radiological evidence of disease after adjuvant chemotherapy could, in theory, eradicate residual disease and increase the chance of cure.”

“This possibility is being further explored in a series of randomized studies that are currently recruiting”, they add.

Reference  

Tie J, Cohen JD, Wang Y, et al. Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage III colon cancer. JAMA Oncol; Advance online publication 17 October 2019. doi:10.1001/jamaoncol.2019.3616