Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis

Abstract

Purpose: To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics.

Patients and methods: We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.

Results: Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY.

Conclusion: The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.

Fig 1.

Decision tree comparing the next-generation sequencing (NGS) panel versus guidelines for evaluation of patients referred to the medical genetics clinic for colorectal cancer and polyposis (CRCP) syndrome evaluation. The decision node (square) indicates a decision point between the two alternative options, whereas the chance nodes (circles) show where two or more alternative events for a patient are possible. Pathways are mutually exclusive sequences of events, and a probability is assigned to each path. Multiplying probabilities along pathways estimates the probability that a relative with the CRCP mutation in question is identified and can therefore receive intensive colorectal cancer (CRC) surveillance (triangles). Only the paths for patients with variants associated with Lynch syndrome are illustrated. AD, autosomal dominant; AR, autosomal recessive. See Appendix (online only) for details.

Fig 2.

Tornado diagram of a one-way sensitivity analysis comparing panel 4 with standard of care. The model inputs at the top of the tornado diagram have the largest effect on the results. Only the top seven most influential parameters are represented. The x-axis scale is in dollars per quality-adjusted life-year (QALY). AD, autosomal dominant; CRC, colorectal cancer; CRCP, colorectal cancer and polyposis syndrome.

Fig 3.

Probabilistic sensitivity analyses of the incremental cost-effectiveness ratio of a comprehensive next-generation sequencing (NGS) panel including genes with highly penetrant syndromes (panel 3) versus standard of care in patients referred to the medical genetics clinic for evaluation of colorectal cancer and polyposis syndrome. Evaluation with NGS panel was cost effective in 74.6% of simulations if society is willing to pay $50,000 per quality-adjusted life-year (QALY) and in 99% of simulations if society is willing to pay $100,000 per QALY.