Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model

Abstract

ObjectivesTo examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC).DesignPrognostic model.SettingDutch biennial FIT-based screening programme during 2014–2018.Participants265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2.InterventionsColonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces).Main outcomesWe evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5–1.0), the degree of risk stratification and C-statistics in external validation.ResultsAmong study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept −0.008 to −0.099; slope 0.982–0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91).ConclusionParticipants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.

Personalized Colorectal Cancer Screening: Study Protocol of a Mixed-methods Study on the Effectiveness of Tailored Intervals Based on Prior F-hb Concentration in a Fit-based Colorectal Cancer Screening Program

“…The design of our study is xed and based on the current test (FIT; FOB-Gold; Sentinel Diagnostics, Milan, Italy), cut-off (47 μg Hb/g feces) and age range (individuals aged 55-75) used in the Dutch CRC screening program. Nevertheless, even if the CRC screening program would be modi ed in terms of test, cut-off or age range, we expect that the results of our study are still relevant: the effect of the risk factor f-Hb holds for all ages, and the literature shows that it also holds for other cut-offs and FIT brands [7,11,[13][14][15][16][17][30][31][32]. Furthermore, even if the decision should be made to use another test instead of FIT, the study is still informative on the acceptability of risk-based screening in general.…”

“…The likelihood that the integration of tailored invitation intervals based on prior f-Hb concentration after negative FIT lowers the participation rate is therefore smaller than if another (not automatically obtained) risk factor would be used to personalize CRC screening. Sex and age are also automatically registered, but their predictive value is much lower than the f-Hb concentration (odds ratios for AN: 1.6 (male sex) and 0.9-1.1 (increasing age) vs. 2.5-21.8 (increasing f-Hb concentrations), respectively [7]). In addition, a strong association was observed between the measured f-Hb concentration in participants with a negative FIT and the risk of developing interval CRC in the Dutch CRC screening program [11].…”

“…There is increasing evidence that f-Hb concentration is a good predictor of future diagnosis of advanced neoplasia (AN) (Table 1). Models incorporating f-Hb concentrations could reach a discriminatory power of about 80% [6][7][8][9][10]. The major advantage of this predictive factor is that the f-Hb concentration is automatically obtained within FIT-based CRC screening programs and thus is readily available information.…”

Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT)

“…The design of our study is fixed and based on the current test (FIT; FOB-Gold; Sentinel Diagnostics, Milan, Italy), cut-off (47 μg Hb/g feces) and age range (individuals aged 55–75) used in the Dutch CRC screening program. Nevertheless, even if the CRC screening program would be modified in terms of test, cut-off or age range, we expect that the results of our study are still relevant: the effect of the risk factor f-Hb holds for all ages, and the literature shows that it also holds for other cut-offs and FIT brands [ 7 , 11 , 13 – 17 , 30 – 32 ]. Furthermore, even if the decision should be made to use another test instead of FIT, the study is still informative on the acceptability of risk-based screening in general.…”

“…The likelihood that the integration of tailored invitation intervals based on prior f-Hb concentration after negative FIT lowers the participation rate is therefore smaller than if another (not automatically obtained) risk factor would be used to personalize CRC screening. Sex and age are also automatically registered, but their predictive value is much lower than the f-Hb concentration (odds ratios for AN: 1.6 (male sex) and 0.9–1.1 (increasing age) vs. 2.5–21.8 (increasing f-Hb concentrations), respectively [ 7 ]). In addition, a strong association was observed between the measured f-Hb concentration in participants with a negative FIT and the risk of developing interval CRC in the Dutch CRC screening program [ 11 ].…”