Invitation to a single FS screening vs. usual care reduced colorectal cancer mortality and incidence at >15 y

The SCORE trial, a randomized controlled trial (RCT) conducted at six centers in Italy, included 34,292 participants ages 55 to 64 years in the general population who expressed an interest in flexible sigmoidoscopy (FS) screening for colorectal cancer (CRC). Participants were randomized to receive a mailed invitation to a single, prescheduled FS screening (n=17,148) or usual care (n=17,144). Incidence of CRC was reduced by 19% (95% CI, 7% to 29%) in the intention-to-treat analysis and by 33% (95% CI, 19% to 44%) in the per-protocol analysis after a median follow-up of 15 years. CRC mortality was also reduced by 22% (95% CI, 2% to 39%) in the intention-to-treat analysis and 39% (95% CI, 16% to 56%) in the per-protocol analysis after a median follow-up of 19 years.

The study was published online in November 2021 by Annals of Internal Medicine and was summarized in the November 2021 ACP Gastroenterology Monthly. The following commentary by David B. King, MBBS, MPH, was published in the ACP Journal Club section of the March Annals.

The SCORE trial examined screening benefits of a single FS in average-risk persons enrolled between 1995 and 1999. The adequately powered and well-conducted trial also reported long-term follow-up at a median 15.4 years for CRC incidence and 18.8 years for mortality.

Screening reduced CRC incidence and CRC mortality overall, and effects were greater in the per protocol than the reported intention-to-treat analysis. It showed a sustained benefit, with incidence in screening and usual care groups diverging over time. The long-term protective effect was reportedly due to removal of adenomatous polyps at screening. The authors asserted this supports the hypothesis of a plateau in the incidence of adenomas in the distal colon in those aged >60 years.

SCORE results are consistent with 3 similar FS screening RCTs: UK Flexible Sigmoidoscopy Screening Trial; US Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; and Norwegian Colorectal Cancer Prevention Trial. All started between 1993 and 2001. Fecal immunochemical test (FIT) screening was introduced to the study regions in Italy between 2005 and 2012.

FS screening did not reduce proximal CRCs in SCORE, even when patients with high-risk polyps detected in the distal segments were referred for follow-up colonoscopy. It seems the benefit of removing proximal polyps was no longer observed after 15 years. The authors suggested additional screening methods (e.g., colonoscopy or supplementing FS with FIT for those aged 65 to 70 y) may improve the effectiveness of screening for proximal lesions.

A recent cost-effectiveness modeling study from New Zealand concluded that including FS in the national bowel screening program would reduce CRC incidence, long-term health costs, and demand for colonoscopy for current screening.

The long-term protective effect from FS screening at age 55 to 64 years supports the safety of using it as a single intervention.