Background
Colonoscopy has been anticipated as a new method for colorectal cancer (CRC) screening, but conclusive results from randomized clinical trials (RCTs) have not yet been obtained. The World Endoscopic Organization (WEO) developed a stepwise approach to assess a new technique, which could predict final outcomes based on test accuracy and program performance in CRC screening.
Objectives
We evaluated the effectiveness of colonoscopy screening using a stepwise approach modified from the WEO method.
Methods
We divided the process into the following main steps for evaluation of colonoscopy screening and conducted a systematic review for each: In Step 1, the efficacy of flexible sigmoidoscopy (FS) was confirmed as a comparator based on RCTs. In Step 2, test accuracy was compared between colonoscopy and other screening methods. In Step 3, program performance indicators were compared using single-round RCTs, and a network meta-analysis was performed. Finally, in Step 4, long-term follow-up outcomes after a single-shot colonoscopy were compared with those of other methods.
Results
Step 1: Over more than 15 years of follow-up, 4 RCTs evaluated the efficacy of FS screening for CRC (Juul, Ann Intern Med, 2022). The pool analysis suggested a 20% reduction in CRC mortality (relative risk 0.80, 95% CI: 0.72-0.88).
Step 2: Fifteen studies assessed the sensitivity of coloscopy compared with CT colonography (CTC) or repeated colonoscopy. One study reported the sensitivity of fecal immunochemical testing (FIT), FS, CTC, and colonoscopy performed simultaneously. The sensitivity for advanced neoplasia (AN)  detection was consistently higher for colonoscopy than for other methods, even when adenoma size was varied.
Step 3: Candidate articles were searched in MEDLINE, Embase, and Igaku-Cyuo-zasshi (a Japanese database) from inception to October 2024 (Terasawa, BMC Medicine, 2025). Ultimately, 18 RCTs evaluating the performance of CRC screening programs were included. In a network meta-analysis of 15 RCTs without crossover, the FIT-based program had a higher advanced neoplasia (AN) detection rate than the guaiac fecal occult blood testing-based program (relative risk [RR] 2.48; 95% credible interval [CrI] 1.52–4.21). Compared with the FS-based program, AN detection rates did not differ in the CTC-based program (RR 1.01; CrI 0.43–2.23; very low certainty) or the colonoscopy-based program (RR 1.03; CrI 0.54–1.78). All the visualization-based programs had higher AN detection rates than the FIT-based program (FS: RR 2.13 [CrI 1.38–3.77]; CTC: RR 2.16 [CrI 1.11–4.51]; and colonoscopy: RR 2.19 [CrI 1.43–3.48]). Low event rates precluded definitive conclusions regarding CRC detection. The colonoscopy-based program had the lowest participation rate.
Step 4: Although no RCTs were conducted across multiple rounds, program performance indicators were compared between one-shot colonoscopy, FS, and repeated FITs.
Conclusions/Implications
The results of the stepwise approach suggest that the effectiveness of colonoscopy screening in real-world settings can be predicted. Although high sensitivity was confirmed for the colonoscopy screening, the program performance was considered insufficient due to low participation rates. As the efficacy of colonoscopy screening remains unclear, the final results of ongoing RCTs should be awaited before its introduction into national screening programs.