A study performed over a 9-year period at 4 Swedish hospitals found that in 58 postsurgical patients with stage I, stage II, or stage III resected colorectal cancer (CRC), positive levels of circulating tumor DNA (ctDNA) appeared to be predictive of disease recurrence.
Participants in the study (age range, 47-83 years) had their levels of ctDNA analyzed 1 month after CRC resection and every 3 to 6 months thereafter. Safe-SeqS was used to detect mutations from blood samples. To get to a test specificity of 98%, researchers used a one-sided P value of .02 as a threshold to determine if a sample was positive (P <.02) or negative (P >.02).
In patients who had a positive ctDNA test, 77% (10 patients) experienced disease recurrence. Based on this, the authors determined that this type of test could complement traditional methods of surveillance, including the measurement of carcinoembryonic antigen (CEA) and the use of computed tomography scans. The serial test also predicted recurrence earlier than other methods typically used to gauge relapse.
None of the 45 patients who had a negative ctDNA value experienced a relapse after a median follow-up of 49 months, and in the 32 patients who did experience relapse, 29 (91%; 95% CI, 75%-95%) had negative ctDNA levels.
Three patients had false-positive results, but the ctDNA levels in these patients became undetectable during the follow-up period. The authors theorized that the false-positives likely occurred because of minimal residual disease at first ctDNA analysis that was eventually resolved by the immune system. “However,” the authors wrote, “we cannot exclude the possibility that these false-positives were the result of some unappreciated technical artifact.”
Because 31% of the 58 patients under investigation received chemotherapy (at their clinicians’ discretion, and without the knowledge of the results of ctDNA analysis), the investigators only considered postchemotherapy samples in their analysis.
The researchers concluded that serial ctDNA surveillance was more sensitive than CEA levels (100% vs 60%) and that it could likely precede radiographic imaging, helping to minimize subsequent radiation exposure. In addition, unlike imaging, ctDNA level evaluation is not reader-dependent.
Optimal lead time for ctDNA was not determined, and the researchers noted that although ctDNA could detect potential recurrence earlier than other methods (and by a median of 4 months earlier in patients who did not receive adjuvant chemotherapy), it took almost 9 months for 10 patients’ ctDNA to become detectable after resection. “This lead time would not be early enough to affect the decision on adjuvant chemotherapy, but it might still be sufficient to allow for earlier implementation of other curative or palliative strategies,” concluded the authors.
Wang Y, Li L, Cohen JD, et al. Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer [published online May 9, 2019]. JAMA Oncol. doi:10.1001/jamaoncol.2019.0512.