Optimal Stopping Ages for Colorectal Cancer Screening

Abstract

Importance: Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient's sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk.

Objective: To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective.

Design, setting, and participants: This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis-Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024.

Exposures: CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results.

Main outcomes and measures: The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $100 000 per QALYG, was evaluated.

Results: The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT.

Conclusions and relevance: In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

Figure 1.. Sex- and Age-Specific Colorectal Cancer Mortality Rates for Cohorts With a Negative Colonoscopy Result 10 Years Before Index Age and Cohorts With ≥1 Negative Fecal Immunochemical Test (FIT) Result Within 5 Years Before Index Age

The points indicate the observed mortality, and error bars indicate 95% CIs. The lines represent the simulated mortality for each index age (76-85 years) over 10 years of follow-up, stratified by number of FITs over the past 5 years.

Figure 2.. Costs per Quality-Adjusted Life-Year Gained (QALYG) for Selected Strategies Stratified by Sex, Comorbidity, and Screening History

The points represent the estimated cost per QALYG with 1 additional colonoscopy and fecal immunochemical test (FIT). The colored lines indicate the smoothed incremental cost-effectiveness ratios calculated from smoothed costs and QALYGs. The dashed horizontal line represents the willingness-to-pay threshold of $100 000 per QALYG.

Figure 3.. Optimal Colorectal Cancer Screening Stopping Age by Modality for Selected Screening Histories

The optimal stopping age is defined as the oldest age at which 1 additional screening is still cost-effective. Figures for other screening histories are provided in eFigures 8-14 in Supplement 1. FIT indicates fecal immunochemical test. ^aScreening after age 75 years is not cost-effective.