The Colorectal Cancer Chemoprevention Acceleration and Improvement Platform (CRC-CHAMP) – Cohort Description

Cohort Description and Eligibility Criteria

We selected patients from the Forzani and MacPhail Colon Cancer Screening Centre (CCSC) in Calgary, Alberta, Canada. The CCSC offers screening-related colonoscopies to asymptomatic patients within screening eligibility age. Participants were recruited between October of 2022 and September of 2023. Study recruitment and data collection were completed in April of 2024. Potentially eligible CCSC patients were identified from the Centre’s pathology database and were invited by mail through the CCSC to participate in the study. Eligible persons were between the ages of 50-59 at the time of consent and had a documented history of high-risk adenomatous polyps diagnosed at the CCSC within the previous 12 months. Indications for a patient’s index colonoscopy were gathered via electronic medical records. A patient was considered to have a history of high-risk polyps if they had at least one villous or tubulovillous polyp of any size, at least one polyp with high-grade dysplasia of any size, an adenomatous polyp measuring ≥1 cm, more than two tubular adenomas <1 cm in size, or any combination of these findings. Any of these findings would indicate an increased risk of future CRC and would alter follow-up surveillance. ⁹ We were primarily interested in chemoprevention for individuals increased CRC risk, so we included those who would likely receive a more intensive surveillance. Exclusion criteria included allergy or hypersensitivities to ASA, pre-existing regular use of ASA or other non-steroidal anti-inflammatory drugs (NSAIDs) or current use of corticosteroid/methotrexate/valproic acid/digoxin, daily use of anti-cancer/anti-platelet drugs. This was to ensure that those involved in the study would not have any medication-related obstacles to continued use of ASA for chemoprevention. We also excluded those with a daily use of greater than 3 units of alcohol, anticipated surgery in the next month, current or past history of GI ulcers or bleeding, cirrhosis or hepatic impairment, bleeding disorders, asthma, nasal polyps, history of colorectal cancer, platelet count <120K or >450K per microlitre, renal insufficiency or history of congestive heart failure. These criteria were to ensure that participants did not have any existing co-morbidities or risk factors which may conflict with ASA administration or increase risk of adverse events.

Study Design

The study was a single-arm (non-randomized), open-label prospective cohort pilot study (NCT05402124) which was divided into three phases (see Table S1). The study began with a 14-day recruitment phase. During this phase, participants gave written consent to being enrolled in the study and to the use of ASA for a 90-day period. After the completion of the recruitment phase, a 90-day active treatment phase was conducted. Persons who agreed to participate were instructed to take 81 mg of ASA daily for 90-days. Participants were contacted by telephone at 30, 60, and 90 days to examine levels of adherence and adverse events. At the end of the 90-day period, participants completed follow-up questionnaires. For 90-days following the active treatment phase, participants were not provided with ASA through the study and were not specifically instructed to continue treatment. No specific advice regarding future use of ASA was given. All participants were contacted via telephone at the end of this period (180 days after initiation) to determine the prevalence of continued use of ASA on their own. During each of these telephone calls, participants were asked to report any adverse events that they may have experienced. Each adverse event was given a score by one physician investigator indicating whether it was unrelated, unlikely, possible, probably or definitely related. We used a standardized form which indicated specific symptoms required for an event to be deemed related to the administration of ASA. Events labelled as unrelated or unlikely were designated as “unrelated” for the purposes of this study. This scale was based on the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 system. ¹⁰ This study conforms to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. ¹¹

Questionnaire Descriptions and Designs

A total of seven questionnaires were administered to participants throughout the study. A brief description of each questionnaire can be found in Table S2. For the purposes of this report, we focused on data obtained from the Health and Lifestyle Questionnaire (HLQ), adherence, and adverse events reported by participants. The HLQ contains questions regarding personal and family health history, cancer screening behaviour, diet, and sociodemographic characteristics. Questions focused on cancer and colorectal polyp history of the participants and their extended family. All patient information has been de-identified.

Statistical Analysis

The demographic characteristics of the participants were summarized using descriptive statistics. Continuous variables were evaluated with means and standard deviations (SD), and categorical variables were evaluated with frequency counts and percentages. We assessed adherence to the medication intervention over the 90-day active treatment phase by patient characteristics. Separate visuals for adherence and adverse events were generated using R. All analyses were conducted using R (version 4.5.0).

Ethics and Regulatory Approval

This study was conducted in compliance with the protocol approved by the Health Research Ethics Board of Alberta (HREBA), International Council for Harmonization of Technical Requirements for Human Use - Good Clinical Practice (ICH GCP), and according to Health Canada regulatory requirements. The project was approved under HREBA.CC-22-0062. This project is registered with ClinicalTrials.gov under registration identification number NCT05402124.

Participant Demographics

Of the 67 participants enrolled in the study, all completed the initial questionnaires as a part of the enrollment process with the exception of three missing responses for the HLQ. Table 1 contains detailed demographic data. The median age at enrollment was 56 years of age (IQR = 5) and the median BMI of participants was 27.2 kg/m² (IQR = 5.7). 30 (44.8%) participants were assigned female at birth and 37 (55.2%) were assigned male at birth. The majority of participants were Caucasian (64.2%, n = 43), with some post-high school education/training (80.6%, n = 54), and were employed at the time of the study (71.6%, n = 48). In more than half of the index colonoscopies, three or more tubular adenomas less than 1 cm in size (70.1%, n = 47) were found. One or more adenomatous polyps greater than 1 cm in size was the second most common finding (26.9%, n = 18), followed by one or more polyps with villous or tubulovillous pathology (1.5%, n = 1), and any polyp with high-grade dysplasia (1.5%, n = 1).

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Table 1.

Demographics of the Participants Enrolled in the CRC-Champ Study. If a Response was Not Received, a “Missing” Category is Displayed

Characteristic (N = 67)	n (%)	Mean [SD]	Median [IQR]
Age of participant (50-60 Years of age)		55.8 [2.4]	56 [5]
Sex of participants
Female	30 (44.8%)
Male	37 (55.2%)
Body Mass index (BMI)		28.2 [5.0]	27.2 [5.7]
BMI categories
<25	18 (26.9%)
25-30	28 (41.8%)
>30	21 (31.3%)
Employment status
Working	48 (71.6%)
Retired	11 (16.4%)
Other (student, unemployed etc.)	5 (7.5%)
Missing	3 (4.5%)
Level of education
University/College degree/Trades certification	54 (80.6%)
No high school degree	1 (1.5%)
Other (High School/GED)	9 (13.4%)
Missing	3 (4.5%)
Self-identified ethnicity
Caucasian	43 (64.2%)
Asian	11 (16.4%)
Other	10 (14.9%)
Missing	3 (4.5%)
Immediate family CRC status
High risk CRC	9 (13.4%)
Low risk CRC	17 (25.4%)
No immediate family history of CRC	41 (61.2%)
Primary indication for performing index colonoscopy
Positive FIT	37 (47.8%)
Personal history of polyps	19 (14.9%)
Family history of polyps or CRC	11 (16.4%)
Eligibility criteria from index colonoscopy
At least one adenomatous polyp ≥ 1 cm in size	18 (26.9%)
At least one polyp with high-grade dysplasia of any size	1 (1.5%)
At least one villous or tubulovillous polyp of any size	1 (1.5%)
Three or more tubular adenomas < 1 cm in size	47 (70.1%)

Patient Adherence and Adverse Events

The study began with 67 participants taking ASA. After the first 30 days of active treatment phase, 60 (89.6%) participants reported that they were still taking ASA, while three participants discontinued treatment (4.5%) and four did not respond (6%) (Figure 2). Among these 63 people, within the first 30 days, there were five reported adverse events, including constipation, acid reflux (GI symptoms) and three unrelated events among three individuals (4.5%) (Figure 3). Two out of these three participants had discontinued the ASA. Between 30 and 60 days, 54 participants were adherent (80.6%), six participants were not (9.0%), with seven participants not responding (10.4%) (Figure 2). During this period, among these 60 people, there were eight adverse events among six people (9.0%) (including abdominal pain/heartburn, bloating, bleeding due to abrasions, bruising/pain, and two unrelated events) (Figure 3). At the end of the follow-up period (90 days), 55 participants were adherent (82.1%), with seven non-adherent participants (10.4%) and five missing responses (7.4%) (Figure 2). Out of these 62 people, there were six adverse events in three participants (one case of bruising, one case of abdominal pain/heartburn and three unrelated events) (Figure 3). Out of the three participants with adverse events at the 90-day follow-up, two were not adherent. Throughout the entire period, 48 (71.6%) participants were adherent at all follow-ups. Overall, out of the 67 participants recruited, nine (13.4%) experienced some adverse event, seven of which had events which were likely related to ASA (Figure 3). The final follow-up at 180 days also revealed that 6 out of 39 (15.4%) participants (who responded to the follow-up), continued to take ASA after the conclusion of the active treatment period.OPEN IN VIEWER

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Figure 3.

Adherence and adverse events of persons taking ASA in this study, between 1 and 3 months. Adverse events labelled as “unrelated” or “unlikely” related are indicated with a grey category. Black dashes indicate that the participant was not adherent during a month. Events are separated based on whether the participant was adherent

Limitations

This pilot study highlighted a limitation of physical mail-based recruitment into research studies. The response rate to our mailouts to potential participants was 15.8% (n = 130/823), which may suggest reconsidering mail-based recruitment for future studies and potentially highlight a need for means of digital recruitment approaches, such as through email or social media. In alignment with our ethics-approved protocol, a detailed recruitment letter was used to inform participants about the study’s background and purpose. The letter included details such as the target population, intervention, and rationale, information on data collection and eligibility, and assurances that the study would not affect or delay their ongoing care.

Future efforts could refine the recruitment materials with additional visual approaches, which may enhance its appeal to potential study participants. While we attempted to target a potentially eligible population, approximately half (53.1%; n = 69/130) of the respondents were deemed eligible after expressing interest. The largest number of people who were not eligible were already taking a non-steroidal anti-inflammatory drug.

In the future, we may also implement strategies to regularly check-in with participants to examine factors which may lead to a lack of adherence. Additionally, future research may attempt to gather further details regarding a participant’s decision to decline chemoprevention. Other factors leading to a lack of response or a refusal to participate may inform future health initiatives.

This study may also not be representative of the general population, as recruitment only took place within a single screening center in Alberta. This approach may have led to under-representation across ethnic and socioeconomic groups. Additionally, the sample size of 67 is too small for thorough statistical analysis, somewhat limiting analysis of various trends and behaviors regarding chemoprevention. The issues discussed may limit the generalizability to other populations. These insights will be useful for refining recruitment strategies and streamlining future enrollment processes. Finally, this study only included a single NSAID over a relatively short follow-up period and was single-arm, meaning there was no other treatment or placebo used as a comparator. The processes developed in the study can be expanded to evaluate a wider range of potential CPAs and compare patient reception, efficacy and level of adverse events.

Strengths

To our knowledge, this pilot study is among the first to evaluate the potential for chemoprevention in a real-world population undergoing screening in Canada. The few occurrences of minor adverse events underscore the tolerability of ASA in this population, making it a viable option for future use. Importantly, the high level of adherence observed indicates that participants are willing to engage in chemoprevention and may have positive perceptions of these interventions. Overall, our findings suggest that real-world implementation of chemoprevention for CRC is feasible, and our platform could be expanded to include other CPAs, such as vitamin D or GLP-1 receptor agonists for broader application. Future longer-term studies are needed to explore adherence rates among persons using ASA as a CPA in addition to adverse events when using ASA for prolonged periods of time.