Abstract
Background:
Few empirical data are available to inform older adults’ decisions about whether to screen or continue screening for colorectal cancer (CRC) based on their prior history of screening, particularly among individuals with a prior negative exam.
Methods:
Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of CRC incidence and mortality among older adults who had a negative colonoscopy ten years earlier, accounting for death from other causes.
Results:
Screen-eligible adults aged 76–85 years who had a negative colonoscopy ten years earlier were found to be at a low risk of CRC diagnosis, with a cumulative incidence of 0.39% (95% CI: 0.31–0.48%) at two years that increased to 1.29% (95% CI: 1.02–1.61%) at eight years. Cumulative mortality from CRC was 0.04% (95% CI: 0.02–0.08%) at two years and 0.46% (95% CI: 0.30–0.70%) at eight years.
Conclusions:
These low estimates of cumulative CRC incidence and mortality occurred in the context of much higher risk of death from other causes.
Impact:
Knowledge of these results could bear on older adults’ decision to undergo or not undergo further CRC screening, including choice of modality, should they decide to continue screening.
Keywords: Cancer screening, colorectal cancer, colonoscopy, mortality
Introduction
Age is a strong predictor of colorectal cancer (CRC) risk and mortality (1), but other characteristics could bear on the decision of older adults to undergo screening for CRC. Recent recommendations from the United States Preventive Services Task Force (USPSTF), American Cancer Society, and the Multi-Society Task Force advise that, for people ages 76–85 years, the decision should be shared between clinicians and patients (2–4). The guidelines further suggest consideration of prior screening history and overall health (3, 4) because the degree to which a person may benefit from screening depends on both their risk of CRC and life expectancy over which the benefit may accrue (5–8). Understanding for whom continued CRC screening could be of great or only marginal benefit (because they have a high or low risk of CRC, respectively) may inform patient and provider decision-making and more targeted test offerings to older adults, which are key components of the USPSTF’s new recommendations for CRC screening in adults 76–85 years old (4).
However, there is great uncertainty about the value of continued screening beyond age 75 (9, 10) and few data are available to inform the decision. Prior studies have shown a low incidence of CRC in the years immediately following a negative colonoscopy (11) or sigmoidoscopy (12), particularly for persons ages 50–75 years. Existing recommendations for older adults are based primarily on microsimulation models of CRC incidence, colonoscopy harms, and life expectancy (13). This evidence gap leaves age as a default (and sometimes preferred) determinant (14), which ignores tremendous variability in biological age and health status (7, 15) among adults aged 76–85 years and may obscure differences in risk of CRC and CRC-related mortality, especially based on screening history. It is unknown how these differences may translate to differences in the cumulative risk of CRC incidence and mortality.
Using a large multi-healthcare system dataset of patients in Washington and California, we provide absolute estimates of CRC incidence and mortality among people aged 76–85 years 10 years after a negative colonoscopy, i.e., at the point in time when they might consider screening again.
Methods
Study Design and Setting
We conducted a retrospective cohort study among older adult members of three Kaiser Permanente integrated healthcare systems: Northern California (KPNC), Southern California (KPSC), and Washington (KPWA). These healthcare systems contribute to the Optimizing Colorectal Cancer Screening PREcision and Outcomes in CommunIty-baSEd Populations (PRECISE) Research Center, part of the National Cancer Institute-funded Population-based Research to Optimize the Screening Process (PROSPR II) consortium (16). Details of these healthcare systems, particularly with respect to the CRC screening process, have been previously published (16). Cumulatively, these populations include more than 1 of every 70 persons of the total United States population and are generally representative of the census demographics of their regional populations (17–20).
All three integrated healthcare systems include older persons. Compared with the broader United States population aged 65 and older, the study population had similar levels of Medicare coverage (~90%) and greater racial and ethnic diversity. Further details about the PRECISE cohort have been published elsewhere (16, 21). The study was conducted in accordance with the U.S. Common Rule. A waiver of consent was granted and the study was approved by Institutional Review Boards (IRB) at the study sites and the University of Washington.
Eligibility Criteria
The study population included patients from the PRECISE cohort who had previously undergone a colonoscopy (for any indication) and were eligible for CRC screening (based on the eligibility criteria enumerated below) sometime between ages 76–85 years (Figure S-1). The population of interest comprised patients older than 75 years, the upper recommended screening age for universal screening, but younger than age 86 years, when guidelines strongly suggest cessation of screening. Between these age cutoffs, patients are recommended to engage in shared decision-making with their clinician about whether to continue screening (4). Patients were included in the study population if they had a negative colonoscopy (i.e., no adenoma or cancer detected) between January 1, 2000 and December 31, 2009, when they were 66–75 years old, and if they were continuously enrolled and alive ten years following that colonoscopy. The time point ten years after colonoscopy was considered to be the study’s index date (i.e., the time point at which the person might consider screening again). To ensure a screening-eligible population, patients with a history of inflammatory bowel disease (IBD), CRC, or gastrointestinal surgery prior to their index date were excluded. Patients with CRC testing between their negative colonoscopy and index date (e.g., lower endoscopy or any positive fecal test during the ten years prior to their index date, or any fecal test during the one year prior to their index date) were also excluded, since these individuals would have been up-to-date or otherwise ineligible for screening at index date. Patients were considered ineligible for screening if they had a computed tomography (CT) colonography, barium enema, or abdominal CT during the 180 days prior to their index date, because these procedures could be used to detect CRC, and thus anyone with a recent procedure would not be eligible for screening in the near term. Patients were excluded if they had no recorded healthcare encounters (acute inpatient stay, institutional stay, or primary care visit) with the healthcare system during the 365 days prior to the index date, which served as a measure of an interaction with a healthcare provider at which symptoms, if present, would have been reported. This exclusion also improves the likelihood of up-to-date coding of other relevant conditions for analysis (e.g., for calculation of comorbidity index described in the “Measures” section below).
Finally, patients with any relevant symptoms (i.e., abdominal pain, iron deficiency or unspecified anemias, gastrointestinal bleeding or blood in stools, diarrhea, weight loss or underweight, diverticulitis, constipation, abdominal mass, or change in bowel habits) during the 180 days prior to their index date were also excluded because the presence of these signs or symptoms makes patients ineligible for screening, which, by definition, occurs in patients without possible signs or symptoms of cancer.
Data Collection
The PRECISE Research Center collected information on patient demographics and clinical characteristics, CRC screening process data (i.e., risk factors, screening tests, diagnostic evaluations, treatment procedures, and outcomes), CRC screening history prior to cohort entry, cancer diagnoses, and cancer deaths. Data on CRC tests, patient demographics, and comorbidities diagnosed during cohort eligibility were obtained from administrative and clinical databases including electronic health records. Patient data regarding prior testing history and conditions were also collected from these sources, with look-back period depending on site constraints: KPWA extended back to 1/1/1993 while KPNC and KPSC looked back to 1/1/2000 for enrollment, visits, and CRC tests, and extended further back (to the full extent of information available in electronic records databases) for CRC diagnoses and gastrointestinal surgeries. CRC diagnoses were obtained from local and central cancer registries: Seattle – Puget Sound Surveillance, Epidemiology and End Results (SEER) registry for KPWA, and the facility-based cancer registries at KPNC and KPSC, which report to the State of California Cancer Registry. Information on patient deaths was sourced from state vital records data, as well as a variety of internal sources (e.g., insurance membership, discharge status on claims, etc.). CRC-related deaths were ascertained using each site’s state death records as the primary source for cause of death. In the rare case where a patient was recorded with a CRC-related death but without a CRC diagnosis date, the date of diagnosis was imputed as the date of CRC-related death.
For procedures occurring after the index date, colonoscopy indication was assigned based on manual chart review and natural language processing or using a modified version of a colonoscopy indication algorithm that incorporates administrative and clinical data (22) and considers data elements related to recent procedures, IBD, signs and symptoms, past findings of CRC screening procedures, and personal history of CRC.
Study Measures
The Charlson Comorbidity Index (CCI) was used to measure comorbidity burden and calculated by applying modified Charlson/Deyo comorbidity algorithm weights (23) to an updated set of diagnosis and procedure codes associated with both inpatient and outpatient visits. CCI was assessed as of the last day of the calendar quarter prior to the index date, using a look-back period of 365 days for relevant codes, and categorized (0, 1, 2, 3, 4, ≥5) for analysis. Sensitivity analyses stratified patients based on the individual comorbid conditions that contributed to the CCI. Other covariates included age at index date, sex, ethnicity and race, and recent encounters with the healthcare system, which were classified as primary care or inpatient stays (both acute and institutional) and used as a supplementary proxy for health status, along with CCI.
Statistical Analysis
Descriptive statistics were calculated to characterize the cohort demographics. Cumulative incidence functions (CIFs) were used to estimate cumulative incidence for two outcomes: 1) CRC incidence and 2) CRC mortality in the years following the index date, with estimates at two-, five-, and eight-years post-index date. Follow-up began at index date (i.e., ten years after a prior negative colonoscopy where no adenoma or CRC was detected; Figure 1) and continued until diagnosis of CRC or death from CRC, aging out of cohort eligibility (96th birthday), disenrollment from health plan, moving out of SEER coverage area, end of cohort follow-up on December 31, 2019, or 180 days after a subsequent screening colonoscopy (mortality and incidence analyses) or fecal test (mortality analysis only). Follow-up was censored for these reasons so the estimates describe CRC incidence and mortality beginning ten years after a negative colonoscopy in the absence of screening interventions that may have affected the risk of the outcome. The exact date of censoring was delayed to 180 days after a screening colonoscopy to avoid the exclusion of cancers detected by the procedure. Follow-up was not censored after a colonoscopy with a diagnostic indication since diagnostic colonoscopy is routine clinical care when indicated, rather than a preventative health measure; thus, a decision about whether to screen would have no impact on the occurrence of a diagnostic procedure. Follow-up for CRC mortality was additionally censored at 180 days after a fecal test (fecal immunochemical test or fecal occult blood test) because the test reduces risk of CRC mortality (24–26); a 180-day censoring delay avoids excluding CRC deaths.
Figure 1.
Follow-up began between ages 76–85 years at the index date, defined as ten years after a negative colonoscopy (which occurred between ages 66–75 years). Screening is universally recommended up through age 75 years and not recommended for ages older than 86 years. Guidelines for ages 76–85 are less clear and lacking in empirical evidence.
A Fine-Gray subdistribution hazard model was used to simultaneously estimate the absolute risk of CRC outcome (incidence or mortality) and non-CRC mortality (27). Deaths from causes other than CRC were counted as competing events (28, 29). The more common method (30, 31) for estimating cumulative incidence of events over time—one minus the Kaplan-Meier (KM) estimate of the survival function—censors follow-up at death from another cause, which means deceased participants are assumed to have the same risk of the outcome (CRC) as the alive individuals remaining in the population. This approach thus misrepresents the incidence of CRC among older adults remaining alive. To demonstrate the effect of this difference in calculation, cumulative mortality and incidence for the total population were also computed using a Kaplan-Meier approach as a secondary analysis. CIF incidence and mortality were stratified by patient demographic and health status variables: age at index date (in years); sex (male vs. female); CCI (0, 1, 2, 3, 4, ≥5); number of primary care encounters or inpatient stays (both acute and institutional) during the 180 days prior to index date.
A sensitivity analysis was also used to estimate cumulative CRC incidence and mortality without censoring after screening colonoscopy, since retrospective classification of colonoscopy indication based on electronic data is known to be imperfect (22) and censoring at a screening colonoscopy could lead to an inaccurate estimate of CRC risk if persons who have a screening colonoscopy after age 75 years are not representative of CRC risks and lifespan.
Data Availability
The data generated in this manuscript are not publicly available due to IRB restrictions to protect patient privacy and consent. Processes for accessing PROSPR data are described at: https://healthcaredelivery.cancer.gov/prospr/datashare/.
Results
Study Population
Characteristics of the 25,974 screen-eligible patients aged 76–85 years at their index date (i.e., with a negative colonoscopy ten years prior) are shown in Table 1. The study population skewed slightly towards younger ages in that range (54.7% aged 76–80 years vs. 45.3% aged 81–85 years). Cohort members were primarily identified as non-Hispanic White (66.2%), Hispanic (13.4%), non-Hispanic Asian (11.3%), and non-Hispanic Black (9.1%). Other racial groups comprised less than 2% among those with a recorded racial identity. There was a higher proportion of females (58.0%) than males (42.0%). In general, the cohort was highly heterogenous in terms of comorbidity burden: nearly one quarter had no major comorbidities (CCI=0) and more than half (54.1%) had a CCI score of two or more. The three most prevalent comorbid conditions at the index date were peripheral vascular disease (37.8%), renal disease (29.3%), and diabetes (24.3%). Characteristics of the study population stratified by healthcare system are shown in Table S-1. We observed slight differences in the distribution of characteristics by healthcare system, with greater racial diversity at KPNC and KPSC and lower comorbidity scores at KPWA (Table S-1).
Table 1:
Characteristics at index date of screen-eligible patients aged 76–85 years with negative colonoscopy ten years earlier.
| All Ages | 76–80 years | 81–85 years | |
|---|---|---|---|
| (N=25974) | (N=14220) | (N=11754) | |
| Characteristic at index datei | n (%) | n (%) | n (%) |
| Age (years) | |||
| 76–80 | 14220 (54.7) | 14220 (100.0) | 0 (0.0) |
| 81–85 | 11754 (45.3) | 0 (0.0) | 11754 (100.0) |
| Sex | |||
| Male | 10914 (42.0) | 5965 (41.9) | 4949 (42.1) |
| Female | 15060 (58.0) | 8255 (58.1) | 6805 (58.1) |
| Ethnicity and Race ii | |||
| Hispanic | 3489 (13.4) | 1900 (13.4) | 1589 (13.5) |
| Non-Hispanic White | 17206 (66.2) | 9327 (65.6) | 7879 (67.0) |
| Non-Hispanic Black | 2360 (9.1) | 1300 (9.1) | 1060 (9.0) |
| Non-Hispanic Asian | 2927 (11.3) | 1680 (11.8) | 1247 (10.6) |
| Non-Hispanic Native American/Alaska Native | 89 (0.3) | 51 (0.4) | 38 (0.3) |
| Non-Hispanic Native Hawaiian/Other Pacific Islander | 104 (0.4) | 66 (0.5) | 38 (0.3) |
| No race information | 3621 (13.9) | 1992 (14.0) | 1629 (13.9) |
| Charlson Comorbidity Index score iii | |||
| 0 | 6193 (23.8) | 3724 (26.2) | 2469 (21.0) |
| 1 | 5164 (19.9) | 2961 (20.8) | 2203 (18.7) |
| 2 | 4834 (18.6) | 2598 (18.3) | 2236 (19.0) |
| 3 | 3001 (11.6) | 1544 (10.9) | 1457 (12.4) |
| 4 | 2423 (9.3) | 1213 (8.5) | 1210 (10.3) |
| ≥5 | 3785 (14.6) | 1885 (13.3) | 1900 (16.2) |
| Missing | 574 (2.2) | 295 (2.1) | 279 (2.4) |
| Comorbid conditions (present in prior year iv ) | |||
| Myocardial infarction | 1947 (7.5) | 995 (7.0) | 952 (8.1) |
| Congestive heart disease | 2015 (7.8) | 958 (6.7) | 1057 (9.0) |
| Peripheral vascular disorder | 9815 (37.8) | 4948 (34.8) | 4867 (41.5) |
| Cerebrovascular disease | 2215 (8.5) | 1061 (7.5) | 1154 (9.8) |
| Dementia | 1317 (5.1) | 499 (3.5) | 818 (7.0) |
| Chronic pulmonary disease | 5358 (20.6) | 2898 (20.4) | 2460 (21.0) |
| Rheumatic disease | 831 (3.2) | 428 (3.0) | 403 (3.4) |
| Peptic ulcer | 148 (0.6) | 59 (0.4) | 89 (0.8) |
| Mild liver disease | 144 (0.6) | 79 (0.6) | 65 (0.6) |
| Diabetes | 6309 (24.3) | 3504 (24.7) | 2805 (23.9) |
| Diabetes with chronic complications | 4699 (18.1) | 2531 (17.8) | 2168 (18.5) |
| Hemiplegia or paraplegia | 174 (0.7) | 93 (0.7) | 81 (0.7) |
| Renal disease | 7613 (29.3) | 3771 (26.5) | 3842 (32.7) |
| Malignancy (incl. leukemia and lymphoma) | 1928 (7.4) | 1024 (7.2) | 904 (7.7) |
| Moderate or severe liver disease | 44 (0.2) | 21 (0.1) | 23 (0.2) |
| Metastatic solid tumor | 429 (1.7) | 238 (1.7) | 191 (1.6) |
| HIV/AIDS | 14 (0.1) | 14 (0.1) | 0 (0.0) |
| Healthcare encounters (≤180 days prior to index date) v | |||
| 0 encounters | 5073 (19.5) | 2915 (20.5) | 2158 (18.4) |
| 1 primary care encounters only | 8557 (32.9) | 4828 (34.0) | 3729 (31.7) |
| 2 primary care encounters only | 5000 (19.3) | 2803 (19.7) | 2197 (18.7) |
| ≥3 primary care encounters only | 5929 (22.8) | 2982 (21.0) | 2947 (25.1) |
| Institutional/acute inpatient stay | 1415 (5.4) | 692 (4.9) | 723 (6.2) |
Index date was defined as ten years after a negative colonoscopy that occurred between ages 66–75 (i.e., index occurs between ages 76–85 years).
Race and ethnicity were treated as an aggregated category. However, some individuals were identified with ≥1 race group so total does not sum to 100%.
Charlson Comorbidity Index score was calculated using patient-level administrative codes from 365 days preceding the start of the calendar quarter in which the index date occurred. For example, an index date of 2/15/10 would use a Charlson score calculated based on data collected between 1/1/09–12/31/09. Calendar quarters began January 1, April 1, July 1, and October 1 annually.
Many individuals had ≥1 individual comorbid conditions (i.e., these are not mutually exclusive categories).
Includes acute inpatient, institutional, and primary care encounters; does not include specialty or telemedicine encounters.
Cumulative CRC Incidence and Mortality
Overall, cumulative CRC incidence and mortality were low in this population. Cumulative incidence of CRC was estimated as 0.39% (95% CI: 0.31–0.48%) two years after index date and 1.29% (95% CI: 1.02–1.61%) eight years after index date (Table 2). Cumulative CRC mortality was an order of magnitude lower: 0.04% (95% CI: 0.02–0.08%) two years after index date and 0.46% (95% CI: 0.30–0.70%) eight years after index date (Table 3). Sensitivity analyses found that these estimates did not change if subsequent screening colonoscopy was not treated as a censoring event (Tables S2 and S3). Estimates for cumulative CRC incidence and mortality are provided in Tables 2 and 3, respectively; corresponding estimates of cumulative mortality from other causes are provided in Table S-4. Cumulative incidence curves that generated overall estimates are illustrated in Figure 2, with additional stratified curves provided in Figure S-2.
Table 2:
Cumulative CRC incidence, stratified by patient characteristics at index date
| Cumulative incidence of CRC, percent (95% CI) | |||
|---|---|---|---|
| 2-year | 5-year | 8-year | |
| All patients (competing risks analysis) | 0.39 (0.31,0.48) | 0.86 (0.71,1.04) | 1.29 (1.02,1.61) |
| All patients (secondary analysis via Kaplan-Meier approach#) | 0.40 (0.31,0.49) | 0.96 (0.77,1.15) | 1.58 (1.16,2.00) |
| Sex and age at index (years) | |||
| 76–80 | 0.35 (0.25,0.48) | 0.87 (0.66,1.12) | 1.36 (0.97,1.86) |
| 81–85 | 0.44 (0.32,0.59) | 0.85 (0.64,1.12) | 1.21 (0.87,1.64) |
| Female | 0.33 (0.24,0.45) | 0.76 (0.57,0.99) | 1.05 (0.74,1.44) |
| Male | 0.47 (0.34,0.64) | 1.00 (0.76,1.3) | 1.61 (1.16,2.18) |
| Female, age 76–80 | 0.28 (0.17,0.43) | 0.73 (0.49,1.05) | 0.98 (0.59,1.55) |
| Female, age 81–85 | 0.40 (0.25,0.60) | 0.79 (0.53,1.15) | 1.11 (0.69,1.71) |
| Male, age 76–80 | 0.45 (0.29,0.69) | 1.06 (0.72,1.51) | 1.86 (1.17,2.82) |
| Male, age 81–85 | 0.49 (0.30,0.75) | 0.93 (0.62,1.36) | 1.34 (0.84,2.04) |
| Charlson Comorbidity Index (CCI) i | |||
| 0 | 0.40 (0.26,0.61) | 0.95 (0.66,1.34) | 1.53 (1.05,2.16) |
| 1 | 0.35 (0.20,0.59) | 0.61 (0.36,0.97) | 0.99 (0.41,2.09) |
| 2 | 0.38 (0.22,0.64) | 0.74 (0.44,1.18) | 1.51 (0.75,2.76) |
| 3 | 0.34 (0.15,0.69) | 0.69 (0.35,1.25) | 0.69 (0.35,1.25) |
| 4 | 0.67 (0.37,1.12) | 1.15 (0.68,1.83) | 1.62 (0.92,2.67) |
| ≥5 | 0.33 (0.17,0.60) | 1.18 (0.71,1.85) | 1.18 (0.71,1.85) |
| Healthcare encounters (≤180 days prior to index date) ii | |||
| 0 encounters | 0.44 (0.27,0.70) | 0.81 (0.50,1.26) | 1.50 (0.90,2.37) |
| 1 primary care encounters only | 0.42 (0.29,0.60) | 1.14 (0.83,1.53) | 1.40 (0.94,2.02) |
| 2 primary care encounters only | 0.39 (0.23,0.64) | 0.74 (0.46,1.14) | 0.96 (0.58,1.51) |
| ≥ primary care encounters only | 0.25 (0.14,0.44) | 0.55 (0.34,0.85) | 1.15 (0.61,2.02) |
| Institutional/acute inpatient stay | 0.55 (0.23,1.17) | 1.13 (0.57, 2.07) | 1.47 (0.71, 2.73) |
| Ethnicity and Race | |||
| Hispanic | 0.54 (0.32,0.88) | 0.91 (0.55,1.43) | 0.91 (0.55,1.43) |
| Non-Hispanic White | 0.37 (0.27,0.48) | 0.82 (0.65,1.04) | 1.34 (1.00,1.75) |
| Non-Hispanic Black | 0.40 (0.18,0.81) | 0.76 (0.40,1.35) | 1.60 (0.62,3.43) |
| Non-Hispanic Asian | 0.29 (0.13,0.6) | 1.09 (0.55,1.96) | 1.09 (0.55,1.96) |
| Non-Hispanic Native American/Alaska Native | 1.22 (0.10,5.93) | 1.22 (0.10,5.93) | 1.22 (0.10,5.93) |
| Non-Hispanic Native Hawaiian/Other Pacific Islander | * | 2.74 (0.20,12.44) | 2.74 (0.20,12.44) |
Kaplan-Meier approach (1-Kaplan-Meier estimator) provides an estimate of cumulative incidence that censors at death from another cause.
No incident outcomes in this group.
Charlson Comorbidity Index score was calculated using patient-level administrative codes from 365 days preceding the start of the calendar quarter in which the index date occurred. For example, an index date of 2/15/10 would use a Charlson score calculated based on data collected between 1/1/09–12/31/09. Calendar quarters began January 1, April 1, July 1, and October 1 annually.
Includes acute inpatient, institutional, and primary care encounters; does not include specialty or telemedicine encounters.
Table 3:
Cumulative CRC mortality, stratified by patient characteristics at index date
| Cumulative mortality from CRC, percent (95% CI) | |||
|---|---|---|---|
| 2-year | 5-year | 8-year | |
| All patients (competing risks analysis) | 0.04 (0.02,0.08) | 0.25 (0.15,0.38) | 0.46 (0.30,0.70) |
| All patients (secondary analysis via Kaplan-Meier approach#) | 0.04 (0.01,0.07) | 0.29 (0.16,0.42) | 0.60 (0.32,0.88) |
| Sex and age at index (years) | |||
| 76–80 | 0.03 (0.01,0.09) | 0.18 (0.09,0.36) | 0.41 (0.19,0.80) |
| 81–85 | 0.04 (0.02,0.11) | 0.30 (0.17,0.52) | 0.52 (0.30,0.85) |
| Female | 0.04 (0.01,0.10) | 0.19 (0.09,0.35) | 0.27 (0.14,0.49) |
| Male | 0.04 (0.01,0.10) | 0.32 (0.17,0.58) | 0.72 (0.39,1.22) |
| Female, age 76–80 | 0.03 (0.01,0.12) | 0.10 (0.03,0.26) | 0.10 (0.03,0.26) |
| Female, age 81–85 | 0.04 (0.01,0.15) | 0.27 (0.11,0.57) | 0.44 (0.20,0.86) |
| Male, age 76–80 | 0.03 (0,0.15) | 0.30 (0.11,0.70) | 0.81 (0.33,1.71) |
| Male, age 81–85 | 0.05 (0.01,0.17) | 0.35 (0.15,0.74) | 0.63 (0.28,1.27) |
| Charlson Comorbidity Index (CCI) i | |||
| 0 | * | 0.28 (0.12,0.61) | 0.68 (0.33,1.27) |
| 1 | 0.03 (0,0.18) | 0.16 (0.04,0.47) | 0.16 (0.04,0.47) |
| 2 | 0.06 (0.01,0.20) | 0.18 (0.06,0.47) | 0.18 (0.06,0.47) |
| 3 | 0.05 (0.01,0.28) | 0.24 (0.04,0.98) | 0.24 (0.04,0.98) |
| 4 | * | 0.17 (0.02,0.91) | 0.68 (0.19,1.91) |
| ≥5 | 0.08 (0.02,0.29) | 0.46 (0.17,1.05) | 0.46 (0.17,1.05) |
| Healthcare encounters (≤180 days prior to index date) ii | |||
| 0 encounters | 0.03 (0,0.19) | 0.25 (0.08,0.67) | 0.81 (0.31,1.79) |
| 1 primary care encounters only | 0.06 (0.02,0.15) | 0.34 (0.16,0.65) | 0.41 (0.20,0.77) |
| 2 primary care encounters only | 0.03 (0,0.15) | 0.21 (0.07,0.56) | 0.38 (0.12,0.99) |
| ≥3 primary care encounters only | 0.03 (0,0.15) | 0.17 (0.06,0.44) | 0.27 (0.09,0.68) |
| Institutional/inpatient stay | * | 0.14 (0.01,0.77) | 0.55 (0.09,2.07) |
| Ethnicity and Race | |||
| Hispanic | 0.08 (0.02,0.29) | 0.33 (0.10,0.89) | 0.33 (0.10,0.89) |
| Non-Hispanic White | 0.04 (0.02,0.09) | 0.24 (0.14,0.40) | 0.44 (0.25,0.73) |
| Non-Hispanic Black | * | 0.19 (0.02,1.02) | 0.77 (0.21,2.13) |
| Non-Hispanic Asian | * | 0.20 (0.02,1.1) | 0.56 (0.11,1.98) |
| Non-Hispanic Native American/Alaska Native | * | * | * |
| Non-Hispanic Native Hawaiian/Other Pacific Islander | * | * | * |
Kaplan-Meier approach (1-Kaplan-Meier estimator) provides an estimate of cumulative incidence that censors at death from another cause.
No incident outcomes in this group.
Charlson Comorbidity Index score was calculated using patient-level administrative codes from 365 days preceding the start of the calendar quarter in which the index date occurred. For example, an index date of 2/15/10 would use a Charlson score calculated based on data collected between 1/1/09–12/31/09. Calendar quarters began January 1, April 1, July 1, and October 1 annually.
Includes acute inpatient, institutional, and primary care encounters; does not include specialty or telemedicine encounters.
Figure 2.
Cumulative incidence curves for (A) CRC and (B) CRC mortality, stratified by age and sex, starting ten years after negative colonoscopy. Due to the lower point estimates for CRC mortality versus incidence, the y-axis differs for the two panels.
Estimates of cumulative risk of death from non-CRC causes were 100-fold higher than their corresponding CRC mortality estimates. Cumulative mortality from non-CRC causes was estimated as 8.24% (95% CI: 7.83–8.66%) two years after index date and 41.45% (95% CI: 38.74–43.16%) eight years after index date (Table S-4).
Stratification by Age and Sex
Point estimates for cumulative CRC incidence and mortality were higher among males compared to females and CRC mortality was higher among 81–85-year-olds compared to 76–80-year-olds (Figure 2). Strata defined by both characteristics showed even more variation across time points (Figure S-2A and S-2E). At two years following index date, the highest incidence was observed among males aged 81–85 years and lowest among females aged 76–80 years.
Stratification by Health Status: Charlson Comorbidity Index and Healthcare Encounters
CCI scores did not have a clear association with cumulative risk of CRC or CRC mortality (Tables 2 and 3). Estimates for specific comorbid conditions are shown in Tables S-2 and S-3. Individuals with diabetes appeared to have an elevated risk of CRC mortality (0.12% two-year risk; 95% CI: 0.05–0.27%) compared to overall study population risks (0.04% two-year risk).
At eight years following index date, patients with no encounters during 180 days prior to index date had nearly equivalent CRC risk to patients with acute inpatient or institutional stays prior to index date (Table 2). For CRC mortality, patients with no encounters had higher risk at eight years (0.81%; 95% CI: 0.31–1.79%) than patients with any recent encounters (Table 3). Meanwhile, the corresponding risk of death from other causes at the same time point was much higher for patients with acute inpatient or institutional stays compared to no encounters (62.83% vs. 40.24%) (Table S4).
Stratification by Ethnicity and Race
CRC risk was not appreciably different across race and ethnicity groups. Eight-year cumulative risk estimates for CRC incidence were 0.91% (95% CI: 0.55–1.43%) for Hispanic patients; 1.34% (1.00–1.75%) for non-Hispanic White patients; 1.60% (0.62–3.43%) for non-Hispanic Black patients; and 1.09% (0.55–1.96%) for non-Hispanic Asian patients (Table 2). Eight-year cumulative risk estimates for CRC mortality were 0.33% (95% CI: 0.10–0.89%) for Hispanic patients; 0.44% (0.25–0.73%) for non-Hispanic White patients; 0.77% (0.21–2.13%) for non-Hispanic Black patients; and 0.56% (0.11–1.98%) for non-Hispanic Asian patients (Table 3). Descriptive estimates were not robust for patients who identified as Native American/Alaska Native or Native Hawaiian/Other Pacific Islander, due to small numbers (≤0.5% study population).
Discussion
In this study, across three integrated healthcare systems in the western United States, adults aged 76–85 years who had a negative colonoscopy ten years earlier and were eligible for screening were at low risk of being diagnosed with CRC and of dying from this disease. These low 8-year CRC incidence and mortality risk estimates occurred in the context of much higher cumulative risks of death from other causes.
These data substantially extend existing information on CRC incidence and mortality by incorporating screening history into estimates, as well as stratifying by health status. SEER estimates for nearly the same age group (75–84 years) are higher: [cumulative incidence of CRC] 0.58% (two-year) and 2.28% (eight-year); [cumulative mortality from CRC] 0.20% (two-year) and 0.78% (eight-year) (32). However, SEER estimates reflect the risks of a population that is heterogeneous and, on average, higher risk than this study population, because SEER includes individuals who may have less-than-adequate screening histories (e.g., none, or longer than ten years ago) and/or prior positive findings on a CRC test.
Importantly, these current estimates account for a critical selection factor that affects most disease risk estimates in older adults: death from other causes. The current analysis acknowledges that death from causes other than CRC is a significant consideration for the assessment of disease risk among older adults. Without accounting for risk of death from another cause (i.e., by using one minus the Kaplan-Meier estimator (1-KM) and censoring patients at time of death), risk estimates of CRC incidence and mortality were higher: 1.58% vs. 1.29% and 0.60% vs. 0.46%, respectively, eight years after index date. Accounting for deaths from other causes in the generation of cumulative risk estimates thus implicitly acknowledges that lower life expectancy ultimately affects cumulative risk of CRC. Since discussions of individual life expectancy are difficult during shared decision-making conversations between older adults and their care providers (33), these cumulative risk figures may be a useful population-level alternative.
Estimates of cumulative incidence and mortality differed little when stratified by a limited set of ethnicity and race identities due to wide confidence intervals, and caution in their interpretation is warranted. While some participants reported belonging to more than one race category, the categories were limited and may not capture the full diversity of the population. Furthermore, although this study cohort of 76–85 year-olds has a higher representation of Black (9.5% vs. 8.8%) and Asian (11.8% vs. 4.0%%) patients than the general United States population (34), representation was still insufficient to provide stratified estimates for other listed race categories. We also caution that stratifying a disease-specific risk estimate by race may exacerbate inequality if a group with higher cumulative risk of other causes of death has lower risk of CRC and thus is denied screening opportunities without confronting the underlying disparities driving the competing risk of death.
There are several strengths and limitations of the current study. Strengths include the high-quality long-term data (including prior testing history) and use of a large and diverse screen-eligible cohort. However, the estimates presented in this analysis are not individual-level risk prediction (as the ability to gauge person-level life expectancy was quite limited) but rather provide empirical evidence of population-level CRC risk among previously tested older adults. These estimates are stratified by univariate characteristics, one or two at a time; individuals are, of course, much more complex. Furthermore, the estimates are specific to a population of individuals with negative colonoscopy ten years ago and do not include patients undergoing surveillance for a polyp or other findings of concern. The risks estimated in this study should be considered in the context of the described population, and any application to a new population setting should evaluate both differences in background rates of CRC as well as population characteristics. Another limitation is that despite efforts made to include a diverse cohort, absolute number of events in ethnicity and race strata were insufficient to produce robust estimates stratified by ethnicity and race.
In summary, this study documents that adults aged 76–85 years who had a negative colonoscopy ten years earlier were at low risk for CRC and CRC-related mortality during the ensuing eight years. Knowledge of these results could well have a bearing on older adults’ decision to undergo or not undergo further CRC screening, including choice of modality, should they decide to continue screening.
Supplementary Material
Acknowledgements
J. Chubak, D.A. Corley, E.A. Halm, A. Kamineni, J.E. Schottinger received funding from the National Cancer Institute at the National Institutes of Health (Grant number: UM1CA222035). This manuscript was written as part of the Population-based Research to Optimize the Screening Process (PROSPR II) consortium. The overall aim of PROSPR II is to conduct multisite, coordinated, transdisciplinary research to evaluate and improve cervical, colorectal, and lung cancer screening processes. This work was also supported by grant number T32CA09168 from the National Cancer Institute.
The views expressed here are those of the authors only and do not necessarily represent the views of the National Cancer Institute or National Institutes of Health.
Footnotes
Conflicts of interest: The authors declare no potential conflicts of interest.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data generated in this manuscript are not publicly available due to IRB restrictions to protect patient privacy and consent. Processes for accessing PROSPR data are described at: https://healthcaredelivery.cancer.gov/prospr/datashare/.