Sessile Serrated Polyp Detection Rate in Asymptomatic Average Risk Individuals with Positive Fecal Immunochemical and Multitarget Stool DNA Test: A Systematic Review And Meta-Analysis

The fecal immunochemical test (FIT) and FIT-DNA test are stool-based tests that are recommended by all recognized gastroenterology societies and the United States Preventative Services Taskforce (USPSTF) for average-risk colorectal cancer (CRC) screening. FIT is adopted as the primary CRC screening tool for the majority of European countries, Canada and Australia and in programmatic approaches to screening in the US. The goal of stool testing is to identify early-stage CRC but optimally would also detect benign precursors to CRC including advanced adenomatous or serrated polyps. Most CRC develop from an adenoma while approximately 20-30% originate from SSPs. Previous studies reported a higher adenoma detection rate (ADR) with FIT-DNA than FIT. However, similar data are lacking for performance of stool-based tests on sessile serrated polyp/lesions (SSPs) detection.

Therefore, we performed a meta-analysis aimed at evaluating the sessile serrated polyp detection rate (SSPDR) of FIT and FIT-DNA test in individuals undergoing average-risk CRC screening.

We performed a comprehensive literature search of multiple databases (until September 2022) to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA for average-risk CRC screening. The outcome was overall detection rates of SSP and advanced serrated polyps (ASP; SSP ≥10 mm). SSPDR and ASPDR were compared between FIT and FIT-DNA cohorts. Subgroup analyses were performed based on FIT cutoff, continent, and study type.

A total of 482,405 patients were included from 23 studies (Table 1). The mean age was 62.3±4.4 years, and there were 52.4% females from 21 studies. The pooled SSLPR for all positive stool-based tests was 5.2% (95% confidence interval [CI], 4.0 - 20.3; I² = 99.5%, 18 studies).The pooled SSPDR in FIT-DNA positive individuals was 11.3% (95% CI, 6.6 – 18.6; I² = 95.4%) which was significantly higher compared to FIT positive individuals (4.1%; 95% CI, 2.9 – 5.6; I² = 99.6%; P = .001) (Figure 1a).

The overall pooled ASPDR was 1.4% (95% CI, 0.81 – 2.3; I² = 96.7%).ASP detection rate was higher in FIT-DNA positive individuals (3.8 %; 95% CI, 1.7 – 8.6; I² = 92.8%) as compared to FIT positive individuals (0.71%; 95% CI, 0.36 – 1.4; I² = 75.4%; P <.01; Figure 1b).

SSPDR in FIT-DNA positive individuals was also significantly higher than FIT positive individuals in North American subgroup (11.3% vs 7.2%; P <.001) (Figure 2a) and FIT ≥10 ug/g group (11.3% vs 5.8%; P <.001) (Figure 2b). Pooled SSPDR was significantly higher in FIT ≥10 ug/g group as compared to FIT ≥20 ug/g group (5.8% vs. 2.1%; P <.006).

Our study reports SSP and ASP detection rate of 5.2% and 1.4% for positive stool-based screening tests in average risk population. FIT-DNA outperformed FIT tests in both SSP and ASP detection. Individuals undergoing colonoscopy after positive FIT-DNA had significantly higher rates of SSL as compared to the FIT ≥10 ug/g group and North American subgroup.

Whether this higher detection of SSPs translates into decreased incidence of CRC will need to be determined in future studies.In addition, different screening interval, qualitative versus quantitative FIT, and different test kits all add to variability in FIT performance. In the era of moving towards non-invasive screening modalities, FIT-DNA with wider screening interval is likely going to outperform FIT, but its long-term impact on further decrease in CRC incidence and mortality remains to be seen.