Comparing the Cost-Effectiveness of Innovative Colorectal Cancer Screening Tests

Elisabeth F. P. Peterse, PhD; Reinier G. S. Meester, PhD; Lucie de Jonge, MSc; Amir-Houshang Omidvari, MD; Fernando Alarid-Escudero, PhD; Amy B. Knudsen, PhD; Ann G. Zauber, PhD; Iris Lansdorp-Vogelaar, PhD

Disclosures

J Natl Cancer Inst. 2021;113(2):154-161. 

In This Article

Results

Projected Outcomes

Without screening, the model predicted 108 CRC cases and 45 CRC deaths per 1000 50-year-olds (Figure 1). The number of CRC cases and deaths ranged from 37 to 59 and from 8 to 15, respectively, for the different screening strategies. The strategy that prevented the most CRC deaths was colonoscopy screening every 10 years, whereas screening with the PillCam every 10 years prevented the fewest.

Figure 1.

Colorectal cancer (CRC) cases and deaths with the different screening strategies. CTC = computed tomographic colonography; FIT = fecal immunochemical test; mSEPT9= methylated SEPT9 DNA plasma assay; mtSDNA = multitarget stool DNA; PillCam = PillCam COLON 2.

In the absence of screening, the model predicted lifetime CRC-related costs of $7.286 million per 1000 50-year-olds (Table 3). None of the alternative screening strategies were cost-saving compared with no screening. Of the alternative strategies, CTC screening every 5 years had the lowest costs ($7.479 million), whereas annual mtSDNA screening was the most expensive ($10.798 million). The number of QALYG compared with no screening ranged from 165 for PillCam screening every 10 years to 205 for annual mtSDNA screening; the number of total colonoscopies required ranged from 1824 per 1000 50-year-olds for CTC every 5 years to 3827 for annual mSEPT9 screening (Table 3).

Cost-effectiveness Analysis

For individuals who are not willing to undergo FIT or colonoscopy screening (ie, those for whom FIT and colonoscopy are not considered acceptable alternatives), CTC every 5 years and annual mSEPT9 were efficient strategies, with ICERs of $1092 and $63 253 per QALYG, respectively (Figure 2; Table 3). Annual screening with the mSEPT9 resulted in a high number of individuals referred to colonoscopy: 51% after 3 years and 69% after 5 years. PillCam strategies were dominated by other strategies, and annual mtSDNA screening had an ICER of $214 974 per QALYG, which is above the willingness-to-pay threshold.

Figure 2.

Efficient frontier. Lifetime costs and quality-adjusted life-years of the evaluated screening strategies. CTC = computed tomographic colonography; FIT = fecal immunochemical test; mSEPT9 = methylated SEPT9 DNA plasma assay; mtSDNA = multitarget stool DNA; PillCam = PillCam COLON 2; QALYG = quality-adjusted life-years gained.

When considering all screening strategies, including FIT and colonoscopy, colonoscopy every 10 years resulted in an ICER of $48 155 per QALYG compared with annual FIT screening and was therefore the cost-effective strategy in this analysis (Table 3; Figure 2). Annual FIT screening was cost saving compared with no screening. All alternative strategies were dominated by FIT and colonoscopy screening. The number of QALYG, CRC cases prevented, and CRC deaths prevented for annual mSEPT9 were higher than for annual FIT screening (Figure 1; Table 3). However, the test burden in terms of number of diagnostic colonoscopies was 63% higher, and the total costs were 26% higher compared with annual screening with FIT (Table 3).

Scenario Analyses

In all our scenario analyses, the same 3 strategies were efficient for individuals not willing to undergo FIT or colonoscopy screening: CTC screening every 5 years, annual mSEPT9, and annual mtSDNA. Our results were robust for alternative assumptions regarding starting age of screening, screening adherence, and systematically missing adenomas or cancers, which resulted in ICERs for annual mSEPT9 of $66 372, $41 041, and $68 682 per QALYG compared with the next-best alternative, respectively (Table 4; Supplementary Table 9, available online). However, when we simulated a lower CRC incidence, annual mSEPT9 resulted in an ICER of $119 336 per QALYG. Hence, CTC screening every 5 years was the cost-effective strategy for these individuals with an ICER of $9397 per QALYG (Supplementary Table 9, available online). Although efficient, annual mtSDNA screening was never cost-effective using a willingness-to-pay threshold of $100 000 per QALYG. When FIT and colonoscopy were also considered, colonoscopy screening every 10 years was the cost-effective strategy in all our scenario analyses (Supplementary Table 9, available online).

Probabilistic Sensitivity Analyses

For individuals who are not willing to undergo FIT or colonoscopy screening, annual screening with mSEPT9 was the cost-effective strategy in 54% of the 1000 simulations evaluated in the probabilistic sensitivity analyses at a willingness-to-pay threshold of $100 000 per QALYG (Figure 3). In 20% and 17% of the simulations, annual mtSDNA screening and CTC screening every 5 years were cost-effective strategies, respectively. At higher willingness-to-pay thresholds, the probability increased that annual mtSDNA screening was the cost-effective strategy, whereas the probability that CTC screening every 5 years was cost-effective decreased. At a willingness-to-pay threshold of $200 000 per QALYG, the probabilities were 48%, 47%, and 1% for mtSDNA, mSEPT9, and CTC, respectively (Figure 3).

Figure 3.

Cost-effectiveness acceptability curve and frontier. CTC = computed tomographic colonography; mSEPT9 = methylated SEPT9 DNA plasma assay; mtSDNA = multitarget stool DNA; PillCam = PillCam COLON 2; QALYG = quality-adjusted life-years gained. *The cost-effectiveness acceptability frontier (CEAF) plots the probability that the optimal screening strategy is cost-effective over a range of cost-effectiveness thresholds.

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