Single CT colonography versus three rounds of faecal immunochemical test for population-based screening of colorectal cancer (SAVE): a randomised controlled trial.

ABSTRACT

BACKGROUND: Colorectal cancer screening is recommended for people aged 50-75 years, but the optimal screening test and strategy are not established. We aimed to compare single CT colonography versus three faecal immunochemical test (FIT) rounds for population-based screening of colorectal cancer. METHODS: This randomised controlled trial was done in Florence, Italy. Adults aged 54-65 years, never screened for colorectal cancer, were randomly assigned (12) by simple randomisation and invited by post to either a single CT colonography (CT colonography group) or three FIT rounds (FIT group; each round was done 2 years apart). Exclusion criteria included previous colorectal cancer, advanced adenoma, or inflammatory bowel disease, colonoscopy within the last 5 years or FIT within the last 2 years, and severe medical conditions. Participants who had a colonic mass or at least one polyp of 6 mm or more in diameter in the CT colonography group and those who had at least 20 µg haemoglobin per g faeces in the FIT group were referred for work-up optical colonoscopy. The primary outcome was detection rate for advanced neoplasia. Outcomes were assessed in the modified intention-to-screen and per-protocol populations. The trial is registered with ClinicalTrials.gov, NCT01651624. FINDINGS: From Dec 12, 2012, to March 5, 2018, 14 981 adults were randomised and invited to screening interventions. 5242 (35·0%) individuals (2809 [53·6%] women and 2433 [46·4%] men) were assigned to the CT colonography group and 9739 (65·0%) individuals (5208 [53·5%] women and 4531 [46·5%] men) were assigned to the FIT group. Participation in the screening intervention was lower in the CT colonography group (1286 [26·7%] of the 4825 eligible invitees) than it was for the FIT group (6027 [64·9%] of the 9288 eligible invitees took part in at least one screening round, 4573 [49·2%] in at least two rounds, and 3105 [33·4%] in all three rounds). The detection rate for advanced neoplasia of CT colonography was significantly lower than the detection rate after three FIT rounds (1·4% [95% CI 1·1-1·8] vs 2·0% [1·7-2·3]; p=0·0094) in the modified intention-to-screen analysis, but the detection rate was significantly higher in the CT colonography group than in the FIT group (5·2% [95% CI 4·1-6·6] vs 3·1% [2·7-3·6]; p=0·0002]) in the per-protocol analysis. Referral rate to work-up optical colonoscopy (the secondary outcome of the trial) was significantly lower for the CT colonography group than for the FIT group after three FIT rounds (2·7% [95% CI 2·2-3·1] vs 7·5% [7·0-8·1]; p<0·0001) in the modified intention-to-screen analysis, whereas no significant difference was observed in the per-protocol analysis (10·0% [8·4-11·8] vs 11·6% [10·8-12·4]). No major complications were observed in the CT colonography group after screening and work-up optical colonoscopy, whereas three cases of bleeding were reported in the FIT group after work-up optical colonoscopy (two after the first FIT and one after the second FIT). INTERPRETATION: Greater participation makes FIT more efficient than single CT colonography for detection of advanced neoplasia in population screening for colorectal cancer. Nonetheless, higher detection rate in participants and fewer work-up colonoscopies are possible advantages of CT colonography as a screening tool, which might deserve consideration in future trials. FUNDING: Government of Tuscany and Cassa di Risparmio di Firenze Foundation. TRANSLATION For the Italian translation of the abstract see Supplementary Materials section.