Haemoglobin level at previous negative FIT and risk of neoplasia at subsequent screening rounds. Carlo SENORE

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1 Haemoglobin level at previous negative FIT and risk of neoplasia at subsequent screening rounds Carlo SENORE

2 Possible conflicts of interest None related to the presentation Carlo Senore

3 AIMS To estimate the risk of advanced neoplasia at subsequent tests among subjects with previous negative FITs by HB concentration measured at previous tests.

4 Population We included in the analysis average risk men and women who performed their first screening FIT between 2004 and 2013 had a second test, or two additional consecutive tests, by December 2014 in the context of the Piedmont Region (target age range 59 to 69) and Aosta Valley and Reggio Emilia (target age range 50 to 74) screening programs 4

5 Screening protocol Single sample FIT (Oc Sensor, Eiken Co. Japan) Positivity cut off: 20 μg Hb /gr faeces (100 ng/ml) Screening interval: 2 years 5

6 We calculated Methods the positivity rate (PR) the detection rate (DR) of advanced adenoma and CRC the positive predictive value (PPV) for advanced neoplasia (advanced adenoma and CRC) at the second screening FIT, following 1 previous negative test at the third screening FIT following 2 previous negative tests. 6

7 Methods We categorised Hb concentration detected in subjects with negative tests into 5 groups: 0 / / / / 20 μg Hb /gr faeces Multivariable logistic models were used to derive an estimate of the association between the Hb concentration in previous rounds and detection rate of advanced neoplasia at the second and third exam, adjusted by gender age (5-year interval) interval since the last negative FIT (months: 22-26; 27-30; 31-36; 36) 7

8 Predictors of CRC or advanced adenomas at the second exam Multivariable logistic regression model GENDER AGE INTERVAL SINCE LAST FIT Hb level at previous FIT μg Hb /gr faeces CRC Advanced adenoma OR 95%CI OR 95%CI Women 1 1 Men months months months > 36 months

9 Predictors of CRC or advanced adenomas at the third exam Multivariable logistic regression model CRC Advanced adenoma OR 95%CI OR 95%CI GENDER Women 1 1 Men AGE months 1 1 INTERVAL SINCE LAST FIT months months > 36 months Hb level FIT1 + FIT2 μg Hb /gr faeces

10 III round results - Men Hb level FIT 1 + FIT2 μg Hb / gr faeces Exams Positive FIT Advanced adenoma CRC Advanced neoplasia N % N % N % N % DR PPV ,1% 716 3,0% 113 0,5% 14 0,06% 0,52% 20,6% ,7% 808 4,6% 129 0,7% 19 0,11% 0,84% 22,5% ,5% 596 7,6% 159 2,0% 14 0,18% 2,21% 34,9% ,2% ,7% 85 3,7% 8 0,35% 4,09% 40,3% ,3% ,3% 88 7,0% 5 0,40% 7,39% 52,8% ,1% ,8% 65 11,4% 13 2,28% 13,66% 56,9% 10

11 III round results - Women Hb level FIT 1 + FIT2 μg Hb / gr faeces Exams Positive FIT Advanced adenoma CRC Advanced neoplasia N % N % N % N % DR PPV ,7% 802 2,6% 74 0,2% 7 0,02% 0,26% 11,8% ,6% 795 3,6% 96 0,4% 16 0,07% 0,51% 17,7% ,7% 507 5,6% 100 1,1% 13 0,14% 1,26% 25,3% ,6% 202 8,6% 49 2,1% 3 0,13% 2,21% 31,5% ,9% ,0% 32 2,6% 5 0,41% 3,04% 37,0% ,6% 96 23,4% 39 9,5% 6 1,46% 10,98% 52,9% 11

12 Conclusion The prevalence of advanced neoplasia at subsequent screening is associated with the Hb level at previous tests A small proportion of people with previous borderline values is showing a substantial increase in the risk of advanced neoplasia at subsequent rounds Subjects who had no haemogobin detected at previous rounds are showing a very low risk. 12

13 Using f-hb concentration to tailor screening recommendations Areas for future research Negative subjects high f-hb concentration Proportion of subjects with 2 negative FIT: 1% 20 µg/gr. faeces ; 2% > 15 µg/gr. faeces TC recall for all these subjects would result in a 15% (20 µg/gr. faeces ), or 53% (> 15 µg/gr. faeces ), increase in the expected TC workload at second round 13

14 Using f-hb concentration to tailor screening recommendations Areas for future research Negative subjects high f-hb concentration Design: parallel cohorts RCT with 3 arms (ratio: 1:1:1) Intervention: A) Immediate referral for TC B) FIT at 1 year + TC referral for those who are positive C) FIT at 2 years + TC referral for those who are positive Outcomes: PPV for and DR of advanced neoplasia Stage distribution of SD CRCs /CRC DR by stage Size distribution of screen detected advanced adenomas IC rate (although the number of ICs is likely to be small) 14

15 Using f-hb concentration to tailor screening recommendations Areas for future research Negative subjects low f-hb concentration Target population: Women with two negative FIT results but cumulative f-hb concentration after 2 rounds =0 (or < 5 μg Hb /gr faeces). Option to include also men with same f-hb concentrtion Size: 30,000 subjects per arm would allow to detect a 100% increase in the IC rate (the same increase now documented between the first and second year, from 0.15 to 0.30 of the expected incidence). Option of using a different ratio between intervention and controls to minimize the number of subjects referred for longer intervals 15

16 Using f-hb concentration to tailor screening recommendations Areas for future research Negative subjects low f-hb concentration Design: parallel arms RCT sequential design (invitation of subjects randomized to 4-year interval could be anticipated based on the observed results in the 3-year arm. Intervention: 3 4 year interval versus 2 years Outcome: Interval CRC rate; stage distribution of SD CRCs /CRC DR by stage 16

17 Acknowledgements Sergio Crotta Paola Cassoni Romano Sassatelli Cinzia Campari Arrigo Arrigoni Mario Fracchia Salvatore Polizzi Nereo Segnan

18 Thank you for your attention