THE EFFECT OF FECAL IMMUNOCHEMICAL TEST THRESHOLD ON COLORECTAL SCREENING OUTCOMES

Purpose:

   The Fecal Immunochemical Test (FIT) is a test commonly used to screen for Colorectal Cancer (CRC) and adenomas.  Liquid based FIT’s permit user specification of the threshold (T) for test positivity with effects on the number testing positive, the likelihood of detecting a neoplasm and the costs of screening. We used the Canadian Risk Management Model CRC sub-model (CRMM-CRC) to predict the effectiveness and cost-effectiveness of CRC screening based upon different choices for T.

Method(s):

    The CRMM-CRC is a micro-simulation model for Colorectal Cancer in Canada. The model includes a natural history spine where CRC’s are assumed to develop from adenomas which are initiated, grow and regress according to age and sex-specific rates. The probabilities of treatment utilization, costs of testing and disease treatment were taken from Canadian data sources.  Published literature on FIT testing by threshold in asymptomatic individuals were reviewed to derive the probability of a positive test (PPT - sensitivity and specificity) for subjects by disease status: CRC, size of adenoma (0-5mm, 6-9mm, 10+mm) and no neoplasm. Models were fit to provide a range of estimates expressing uncertainty in actual PPT values for the different disease states as a function of T.  Effectiveness and cost-effectiveness predictions were obtained by simulating the lifetime of cohort age 45 in 2014. Screening was assumed to occur biennially between ages 50 and 74 with evaluation of abnormal tests by colonoscopy using different threshold values. Costs and QOL adjusted life-years were both discounted at 3%.

Result(s):

   Uncertainty in threshold specific PPT’s were modeled for T between 50 and 225ng/ml in two dimensions: slope – rate of change in positivity rates by T and average – positivity rates at T=100 ng/ml. There were 7 resulting parameter sets evaluated representing joint sensitivity analyses by varying slope and average.  All individual scenario combinations (parameter & T) resulted in predicted reductions in CRC incidence (range=22%-53%) and mortality (35%-65%).  Costs per QOL varied between CAD$-530 and $5,558 across the individual scenarios. Within each parameter set the lowest threshold evaluated had the highest effectiveness but was not necessarily the most cost-effective.

Conclusion(s):

   In the Canadian context screening with FIT for CRC is predicted to be a cost-effective intervention. Low thresholds for abnormality would appear preferable where colonoscopy resources allow.