FIT and Colonoscopy in Familial Colorectal Cancer Screening
FIT and Colonoscopy in Familial Colorectal Cancer Screening
Background & Aims Colonoscopy is the recommended screening procedure for first-degree relatives of patients with colorectal cancer (CRC), but few studies have compared its efficacy for CRC detection with that of other screening strategies. We conducted a controlled randomized trial to compare the efficacy of repeated fecal immunochemical tests (FITs) and colonoscopy in detecting advanced neoplasia (advanced adenoma or CRC) in family members of patients with CRC.
Methods In a prospective study, 1918 first-degree relatives of patients with CRC were randomly assigned (1:1 ratio) to receive a single colonoscopy examination or 3 FITs (1/year for 3 years; OC-Sensor; cutoff ≥10 μg hemoglobin/g feces, corresponding to 50 ng hemoglobin/mL buffer). The strategies were considered to be equivalent if the 95% confidence interval of the difference for the detection of advanced neoplasia was ±3%. Follow-up analyses were performed to identify false-negative FIT results and interval CRCs.
Results Of all eligible asymptomatic first-degree relatives, 782 were included in the colonoscopy group and 784 in the FIT group. In the intention-to-screen analysis, advanced neoplasia was detected in 33 (4.2%) and 44 (5.6%) first-degree relatives in the FIT and colonoscopy groups, respectively (odds ratio = 1.41; 95% confidence interval: 0.88–2.26; P = .14). In the per-protocol analysis, 28 first-degree relatives (3.9%) in the FIT group and 43 (5.8%) in the colonoscopy group had advanced neoplasia (odds ratio = 1.56; 95% confidence interval: 0.95–2.56; P = .08). FIT missed 16 of 41 advanced adenomas but no CRCs. The FIT strategy required endoscopic evaluation of 4-fold fewer individuals to detect 1 advanced neoplasia than the colonoscopy strategy.
Conclusions Repeated FIT screening (1/year for 3 years) detected all CRCs and proved equivalent to colonoscopy in detecting advanced neoplasia in first-degree relatives of patients with CRC. This strategy should be considered for populations where compliance with FITs is higher than with colonoscopy. ClinicalTrials.gov number: NCT01075633 (COLONFAM Study).
First-degree relatives of patients with nonsyndromic colorectal cancer (CRC) are at higher risk of developing CRC than the general population. Personal risk in these individuals has mostly been related to the age of the index case at diagnosis, degree of kinship, and number of relatives affected. Having a first-degree relative with CRC diagnosed after the age of 60 years is associated with an almost 2-fold increase in personal risk, and this increases to 4-fold when CRC in the index case is diagnosed before the age of 55 years. In addition, the risk of developing advanced adenoma or CRC is about 3-fold higher if a sibling is affected and even higher when there are 2 or more first-degree relatives with CRC, regardless of age at diagnosis. Based on this evidence, current practice guidelines recommend that subjects with CRC familial aggregation should be subject to more intensive screening strategies than the average-risk population. Although there is no uniform approach among scientific societies, most recommend colonoscopy every 5 years, starting at the age of 40, or 10 years younger than the index case at diagnosis. These recommendations are based on empirical evidence, as no study has clearly demonstrated the efficacy of this policy to reduce CRC mortality or incidence in this population. However, the efficacy of colonoscopy screening in asymptomatic first-degree relatives of patients with CRC is clearly hampered by suboptimal compliance. Two major factors contribute to this low screening uptake. First, screening in these individuals is mostly opportunistic, as they are currently excluded from population-based programs in most countries; and second, there is ample evidence showing underutilization of colonoscopy at the recommended intervals in this population.
Tentative solutions to improve screening uptake in familial CRC include incorporating these individuals in average-risk population-based programs, as recently recommended by the European Guidelines, and/or offering them alternative screening strategies with inferior detection yield but better acceptance than colonoscopy. In this regard, observational studies have shown that fecal immunochemical testing (FIT) has acceptable performance for detecting colorectal neoplasia in asymptomatic first-degree relatives of patients with CRC. Although randomized controlled trials on the efficacy of FIT vs colonoscopy in familial CRC are lacking, observational studies suggest that FIT has acceptable performance for detecting advanced neoplasia (advanced adenoma or CRC) in asymptomatic first-degree relatives of patients with CRC. In addition, a recent study suggested that using FIT in the intervals of surveillance colonoscopies is useful to detect missed or rapidly developing colorectal neoplasms in this moderate-risk population. All together, these data support the notion that FIT screening could be an alternative strategy to colonoscopy in the familial-risk population, with better screening uptake and acceptable performance.
We hypothesized that repeated FIT screening is equivalent to one-time colonoscopy for detecting advanced colorectal neoplasms in familial CRC. We therefore conducted a controlled randomized trial to compare the efficacy of annual FIT vs one-time colonoscopy for detecting advanced neoplasia in asymptomatic first-degree relatives of patients with CRC.
Abstract and Introduction
Abstract
Background & Aims Colonoscopy is the recommended screening procedure for first-degree relatives of patients with colorectal cancer (CRC), but few studies have compared its efficacy for CRC detection with that of other screening strategies. We conducted a controlled randomized trial to compare the efficacy of repeated fecal immunochemical tests (FITs) and colonoscopy in detecting advanced neoplasia (advanced adenoma or CRC) in family members of patients with CRC.
Methods In a prospective study, 1918 first-degree relatives of patients with CRC were randomly assigned (1:1 ratio) to receive a single colonoscopy examination or 3 FITs (1/year for 3 years; OC-Sensor; cutoff ≥10 μg hemoglobin/g feces, corresponding to 50 ng hemoglobin/mL buffer). The strategies were considered to be equivalent if the 95% confidence interval of the difference for the detection of advanced neoplasia was ±3%. Follow-up analyses were performed to identify false-negative FIT results and interval CRCs.
Results Of all eligible asymptomatic first-degree relatives, 782 were included in the colonoscopy group and 784 in the FIT group. In the intention-to-screen analysis, advanced neoplasia was detected in 33 (4.2%) and 44 (5.6%) first-degree relatives in the FIT and colonoscopy groups, respectively (odds ratio = 1.41; 95% confidence interval: 0.88–2.26; P = .14). In the per-protocol analysis, 28 first-degree relatives (3.9%) in the FIT group and 43 (5.8%) in the colonoscopy group had advanced neoplasia (odds ratio = 1.56; 95% confidence interval: 0.95–2.56; P = .08). FIT missed 16 of 41 advanced adenomas but no CRCs. The FIT strategy required endoscopic evaluation of 4-fold fewer individuals to detect 1 advanced neoplasia than the colonoscopy strategy.
Conclusions Repeated FIT screening (1/year for 3 years) detected all CRCs and proved equivalent to colonoscopy in detecting advanced neoplasia in first-degree relatives of patients with CRC. This strategy should be considered for populations where compliance with FITs is higher than with colonoscopy. ClinicalTrials.gov number: NCT01075633 (COLONFAM Study).
Introduction
First-degree relatives of patients with nonsyndromic colorectal cancer (CRC) are at higher risk of developing CRC than the general population. Personal risk in these individuals has mostly been related to the age of the index case at diagnosis, degree of kinship, and number of relatives affected. Having a first-degree relative with CRC diagnosed after the age of 60 years is associated with an almost 2-fold increase in personal risk, and this increases to 4-fold when CRC in the index case is diagnosed before the age of 55 years. In addition, the risk of developing advanced adenoma or CRC is about 3-fold higher if a sibling is affected and even higher when there are 2 or more first-degree relatives with CRC, regardless of age at diagnosis. Based on this evidence, current practice guidelines recommend that subjects with CRC familial aggregation should be subject to more intensive screening strategies than the average-risk population. Although there is no uniform approach among scientific societies, most recommend colonoscopy every 5 years, starting at the age of 40, or 10 years younger than the index case at diagnosis. These recommendations are based on empirical evidence, as no study has clearly demonstrated the efficacy of this policy to reduce CRC mortality or incidence in this population. However, the efficacy of colonoscopy screening in asymptomatic first-degree relatives of patients with CRC is clearly hampered by suboptimal compliance. Two major factors contribute to this low screening uptake. First, screening in these individuals is mostly opportunistic, as they are currently excluded from population-based programs in most countries; and second, there is ample evidence showing underutilization of colonoscopy at the recommended intervals in this population.
Tentative solutions to improve screening uptake in familial CRC include incorporating these individuals in average-risk population-based programs, as recently recommended by the European Guidelines, and/or offering them alternative screening strategies with inferior detection yield but better acceptance than colonoscopy. In this regard, observational studies have shown that fecal immunochemical testing (FIT) has acceptable performance for detecting colorectal neoplasia in asymptomatic first-degree relatives of patients with CRC. Although randomized controlled trials on the efficacy of FIT vs colonoscopy in familial CRC are lacking, observational studies suggest that FIT has acceptable performance for detecting advanced neoplasia (advanced adenoma or CRC) in asymptomatic first-degree relatives of patients with CRC. In addition, a recent study suggested that using FIT in the intervals of surveillance colonoscopies is useful to detect missed or rapidly developing colorectal neoplasms in this moderate-risk population. All together, these data support the notion that FIT screening could be an alternative strategy to colonoscopy in the familial-risk population, with better screening uptake and acceptable performance.
We hypothesized that repeated FIT screening is equivalent to one-time colonoscopy for detecting advanced colorectal neoplasms in familial CRC. We therefore conducted a controlled randomized trial to compare the efficacy of annual FIT vs one-time colonoscopy for detecting advanced neoplasia in asymptomatic first-degree relatives of patients with CRC.
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