From the AGA Journals

Combo testing improves CRC screening participation, but not advanced disease detection

View on the News

Strategies of choice

Multiple strategies have been validated for CRC screening, showing different characteristics that may affect their acceptability. Indeed, dislike of specific tests has been reported as a barrier to screening for some patients. While adopting more than one method to account for subjects’ preferences would then seem a potentially effective approach to increase uptake, most population-based programs are offering only one screening modality.

The PICCOLINO study, conducted within the Polish CRC screening program, showed that offering fecal immunochemical tests (FIT) together with colonoscopy, either as an active choice or in sequence, may substantially improve participation as compared with the offer of colonoscopy alone.

The combination approaches offered the opportunity to respond to the screening invitation also to those subjects who prefer a noninvasive test, which may have limited the impact of organizational barriers on participation. Making the test immediately available with the invitation letter likely helped enhance the response rate in the choice group, which may explain the high proportion of subjects opting for FIT. Offering FIT might also reduce disparities related to distance from the endoscopy center seen when using primary colonoscopy screening. A longer follow-up is needed to assess the neoplasia yield of the combination strategies, accounting for the cumulative detection rate of FIT over several rounds.

This study shows that implementing combination approaches within population-based programs represents a feasible option, although the low compliance with referral for colonoscopy assessment would suggest the need to implement communication efforts specifically addressing negative attitudes to colonoscopy among subjects opting for FIT.

Carlo Senore, MD, MSc, is an epidemiologist at the epidemiology and screening unit–CPO at the University Hospital Città della Salute e della Scienza in Turin, Italy; he is the director of Piedmont Region Screening Committee. He has no conflicts.



Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

  • Control group: colonoscopy, with nonresponders receiving the same invitation again
  • Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
  • Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Next Article: