Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results

Abstract

Importance: The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results.

Objective: To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors.

Design, setting, and participants: In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020. Data from the National Health and Nutrition Examination Survey (NHANES) from the January 1, 2017, to December 31, 2018, cycle were used to compare the risk profile distribution with that of the general US population. Data analysis was performed from October 2023 to August 2024.

Exposures: Time-varying status of NCS results and risk score.

Main outcomes and measures: Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs for incidence and mortality of CRC.

Results: A total of 195 453 participants (median [IQR] age, 44 [37-56] years at baseline; 81% female) were followed up for a median (IQR) of 12 (6-20) years. Among 81 151 individuals with NCS results and 114 302 without endoscopy, 394 and 2229 CRC cases and 167 and 637 CRC deaths, respectively, were documented. Negative colonoscopy screening results were consistently associated with lower CRC incidence (HR, 0.51; 95% CI, 0.44-0.58) and mortality (HR, 0.56; 95% CI, 0.46-0.70) for 20 years. Among individuals with NCS results, those with an intermediate risk (scores, 6-7) and low risk (scores, 0-5) did not reach the 10-year cumulative incidence of CRC (0.78%) of the high-risk individuals (scores, 8-12) until 16 and 25 years after initial screening, respectively.

Conclusion and relevance: These findings provide evidence for shared decision-making between patients and physicians to consider extending the rescreening intervals after an NCS result beyond the currently recommended 10 years, particularly for individuals with a low-risk profile. These results showed, as a proof of concepts, the importance of considering known CRC risk factors when making decisions for colonoscopy rescreening.

Figure.. Kaplan-Meier Estimates of Colorectal Cancer (CRC) Incidence Since the First Negative Colonoscopy Screening (NCS) Result According to the Categories of the Risk Score in the Nurses’ Health Study (NHS), NHS II, and the Health Professional Follow-Up Study (HPFS)

The risk scores ranged from 0 to 12, with 1 point given for each of the following risk factors: history of first-degree relatives with colorectal cancer (yes or no), age (≤50, >50-≤60, >60-≤70, or >70 years), sex (female or male), current cigarette smoking or past smoker with 5 or more pack-years (yes or no), body mass index of 25.0 or greater (calculated as weight in kilograms divided by height in meters squared) (yes or no), tall stature (upper 50% of height in meters in each cohort) (yes or no), physical activity less than 7.5 metabolic equivalent hours per week (yes or no), heavy alcohol intake (>1 drink [14 g of alcohol] daily for women and >2 drinks [28 g of alcohol] daily for men) (yes or no), no regular aspirin or nonsteroidal anti-inflammatory drug use (<2 tablets or times per week) (yes or no), and unhealthy diet (yes or no). For diet, 1 point was given if fewer than 3 of the 5 dietary recommendations by the World Cancer Research Fund/American Institute for Cancer Research were followed, including less than 0.5 serving daily of red meat, less than 0.2 serving daily of processed meat, 30 g/d or more of dietary fiber, 3 servings daily or more of dairy products, and 48 g/d or more of whole grains or at least half of total grains. For age, points were given accordingly: 0 point for 50 years or younger, 1 point for older than 50 years to 60 years or younger, 2 points for older than 60 years to 70 years or younger, and 3 points for older than 70 years. The red dotted line indicates the 10-year cumulative incidence of colorectal cancer for individuals with a high-risk score (score, 8-12); blue dotted line, the benchmark of the 10-year risk of colorectal cancer at 50 years of age, estimated by the Surveillance, Epidemiology, and End Results program; and solid black lines, the years of follow-up when the 3 risk scores reach the 10-year cumulative incidence of colorectal cancer of the high-risk score (scores, 8-12). NNS indicates numbers needed to screen.