Background
Studies of colorectal cancer (CRC) screening by multi-target stool DNA (MT-sDNA) show false positive (FP) rates of 7–13%. It is unclear whether FP patients are at increased long-term risk of adverse outcomes.
Methods
We compared subsequent clinical events among patients with apparent FP MT-sDNA to those in patients reported as true negative (TN). This was a retrospective cohort study of participants in pre-FDA approval MT-sDNA studies having non-advanced or negative baseline colonoscopy findings from a single referral-center. Per-protocol and calibrated cutoffs defined FP and TN groups. From the time of stool collection, we measured differences between FP and TN groups in time to death, subsequent cancer diagnosis and onset of alarm symptoms.
Results
Of 1050 eligible patients, only 6 were lost to follow-up. Median age was 65.6 years (IQR, 56.8, 72.3); 54% were female. Median follow-up time was 4 years (IQR, 3.5-5.3). Eight aerodigestive (lung & gastrointestinal tract) cancers occurred. FP status by calibrated, but not per-protocol cut-offs was associated with subsequent aerodigestive cancer; however, cumulative incidence did not exceed SEER expectations from the general population. By any cut-off method, FP status was not associated with mortality or alarm symptoms.
Conclusions
While FP status was associated with long-term aerodigestive cancers, new cases were not temporally related and did not exceed incidence estimates from general population.
Impact
These observations do not justify aggressive follow-up evaluation for patients with FP MT-sDNA at this time. Larger studies are needed to confirm these early findings.