Background and Aims:
Prior studies showed that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages highly depend on a patient's sex, health, and screening history. However, these studies were not directly informed by stratified data on CRC risk. This study uses community-based estimates of CRC risk by sex, comorbidity, and screening history from three distinct integrated healthcare systems to inform the optimal age to stop screening.
Methods:
We validated the Microsimulation Screening Analysis-Colon model and estimated clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with one additional fecal immunochemical test (FIT) or colonoscopy. Simulated cohorts aged 76-90 years varied by sex, comorbidity status (none, low, moderate, severe), and screening history (FIT, colonoscopy, or combination). We defined the optimal stopping age for FIT and colonoscopy screening as the oldest age with an incremental cost-effectiveness ratio (ICER) below $100,000/QALYG.
Results:
For women aged 76 years without comorbidities and without prior screening, an additional colonoscopy prevented 17.6 deaths and saved 101.4 life-years per 1,000 persons, and it cost $12,093 per QALY gained. Factors associated with reduced incremental benefit and cost-effectiveness included male sex (ICER, $21,170/QALYG), older age (ICER, $12,093 - $726,436/QALYG for ages 76-90), higher comorbidity (ICER, $12,093-$50,607/QALYG for no-severe comorbidity), and more intensive, recent screening histories (ICER, $16,895-$44,488/QALYG for one prior FIT to a colonoscopy 15 years prior and 5 recent FIT). The optimal age to stop colonoscopy screening varied from ≤75 years for men with severe comorbidity and a colonoscopy 10 years prior to 86 years for women without comorbidities and one prior FIT.
Conclusion:
Sex, screening history, and comorbidity progressively impact the benefits and cost-effectiveness of CRC screening. Personalizing CRC screening for these characteristics leads to a range of optimal stop ages of more than ten years. These results can inform guideline development and patient-directed informed decision-making.
Keywords: Colorectal cancer, screening, stop age

Figure 1. Optimal CRC screening stopping age by modality for selected screening histories. The optimal stop age was defined as the oldest age at which one more screening is still cost-effective.
* screening after age 75 is not cost-effective.
COL = colonoscopy; FIT = fecal immunochemical test.