Risk factors and clinical consequences of interval cancers arising within faecal immunochemical testing-based colorectal cancer screening programme.

Background: Colorectal cancer (CRC) screening programmes aim to detect early, asymptomatic cancers and improve survival. This study aimed to establish the proportion of interval cancers, and the consequences with regard to stage, clinical outcome, and overall survival. Risk factors associated with interval CRCs were investigated.

Methods: The Scottish Bowel Screening Programme uses faecal immunochemical testing at a threshold of 80 µg haemoglobin per g as a positive trigger for investigation. Screening was offered to all eligible individuals in one region, from November 2017 to October 2021. Cancer registries were cross-checked to ensure complete capture of all cancers including interval CRCs. The primary outcome was rate of interval CRCs among participants with follow-up of 24 months, and its relationship to faecal immunochemical testing results, clinical variables, stage, time to diagnosis, and survival. The secondary outcome was identification of risk factors associated with interval CRCs.

Results: The Scottish Bowel Screening Programme generated 316 583 tests during the study period. Participation was 71.0% of the eligible population (212 664 patients); it was greater among women (71.9 versus 70.0%; P < 0.001) and in higher socioeconomic areas (76.9 versus 58.6%; P < 0.001). In the screened population, 546 CRCs were diagnosed within 2 years of screening. Some 289 of these patients (52.9%) had positive bowel screening. There were 257 patients with interval CRCs, who waited a median of 13 (interquartile range 7-20) months for diagnosis. Of CRCs diagnosed, 24.9% had screening faecal immunochemical test results of < 10 µg haemoglobin per g. The interval CRC rate was greater in women, older patients, and among the least socioeconomically deprived. Interval CRCs were associated with worse 2-year all-cause mortality than screen-detected CRCs (23.0 versus 10.8%; P < 0.001). Importantly, 121 of the 257 interval CRCs (47.1%) had detectable faecal immunochemical test results at 10-79 µg haemoglobin per g.

Conclusion: Patients with interval CRCs and a detectable faecal immunochemical test result below the predetermined threshold appear to be significantly disadvantaged with respect to stage at presentation and survival. Almost half of interval CRCs diagnosed within 2 years had detectable haemoglobin on screening faecal immunochemical test and would be a target for lower positivity thresholds.