WEO CRC SC Meeting Barcelona, Spain October 23, 2015
THE HEMOGLOBIN CONCENTRATION IN A NEGATIVE RESULT AS A PREDICTOR FOR ADVANCED NEOPLASIA Isabel Portillo, Eunare Arana-Arri, Isabel Idigoras, Lorea Martínez-Indart. Colorectal Cancer Screening Programme. Basque Country. mariaisabel.portillovillares@osakidetza.eus
No conflicts of interest
THE BASQUE COUNTRY PROGRAMME Coverage 100 80 60 40 20 0 98.6 100 85 72.2 70 56.6 31.4 32 25 5.6 5.6 4 2009 2010 2011 2012 2013 2014 Objective: To decrease CRC incidence and mortality by detection and treatment of premalignant and malignant lesions First round Second round Third round
THE BASQUE COUNTRY PROGRAMME STRATEGY POPULATION BASED 50-69 year-olds (586,700 people) FIT biennial. Cut-off 20µg Hb/g OC-Sensor from 2010 Colonoscopy under sedation as confirmatory test Information system linked with medical database and cancer registries Primary Care Involved Centralized coordination MAIN RESULTS TOTAL INVITED 958,450 PARTICIPATION RATE 68.5% POSITIVE RATE 6.2% COLONOSCOPY UPTAKE 93.7% CCR DETECTION RATE 3.4 AA DETECTION RATE 23.3 AN DETECTION RATE 26.7 PPV CCR 5.4% PPV AA 37.5% PPV AN 42.9%
HYPOTHESIS There is a relationship between the Hb concentration in negative cases and lesion detected in successive rounds A pattern of bleeding could predict the lesion detected after a negative result in successive rounds
OBJECTIVES To know the association between Hb concentration in positives cases with an Advanced Neoplasia detected and their previous negative results. To know the pattern of this association by sex, age group, type of lesion compared with no adenomatous lesion. To know the pattern of this association in CRC by localization and stage.
METHODS 2 GROUPS 1. Participants who had three rounds with two previous negative results and a lesion detected in the third round 2. Participants who had a previous negative result and a lesion detected in successive round Lesions: Colorectal Cancer, Advanced Adenoma, Advanced Neoplasia (CRC+AA) and Low Risk Adenoma. No lesions: negative FIT and positive FIT and negative colonoscopy for CRC, adenoma or other bleeding colonic pathology. Faecal Hb concentrations differences between lesion detected and previous negative result were analyzed (Mann-Whitney test) Logistic regression: to analyze the association of Hb concentration with the diagnosis of Advanced Neoplasia
LIMITATIONS Previous lesion before the debut as positive cases are unknown (only in positive cases the colonoscopy was performed) Comparison in irregular attendees was not analyzed Other risk factors such as lifestyle, morbidity and deprivation were not taken into consideration for this study
µg Hb/g µg Hb/g MAIN RESULTS GROUP 1 GROUP 2 First Round 45,185 NEGATIVE FIT Previous Round 178,307 NEGATIVE FIT Second Round Third Round 45,185 NEGATIVE FIT 2.169 POSITIVE FIT 43,016 NEGATIVE FIT Second Round 10,772 POSITIVE FIT 167,535 NEGATIVE FIT 72 CRC 654 AA 726 AN 367 LRA 911 NEGATIVE COLONOSCOPY 417 CRC 3,260 AA 3,677 AN 1,799 LRA 3,640 NEGATIVE COLONOSCOPY RISK OF A COLONIC ADENOMA/CRC AFTER A PREVIOUS NEGATIVE RESULT Interval of 4 years 1.004 1.002 1.002 1.002 1.001 1.001 1.001 1.001 1.000 1.000 0.999 0.998 1.002 1.043 1.035 1.028 1.061 1.054 1.046 Interval of 2 years 1.002 1.001 1.000 1.001 1.000 CRC AA AN LRA Group 1 CRC AA AN LRA Group 2
µd Hb/g 0 100 200 300 400 500 µd Hb/g 0 20 40 60 80 100 120 µd Hb/g 0 50 100 150 GROUP 1: DIFFERENCES IN HB CONCENTRATION BETWEEN THIRD ROUND AND FIRST ROUND BY LESION BOTH SEX Round 1 (µg Hb/g) Round 3-Round 1 (µg Hb/g) LESIONS IN ROUND 3 CRC (72) 0.8 0.0-3.8 <0.001 104.1 38.8-302.9 <0.001 AA (654) 1.8 0.0-5.6 <0.001 45.6 28.8-98.3 <0.001 AN (726) 1.8 0.0-5.4 <0.001 47.7 29.9-109.8 <0.001 LRA (367) 0.8 0.0-3.4 <0.001 42.0 26.8-79.6 <0.001 NO LESIONS IN ROUND 3 (43,733) 0.0 0.0-0.8 0.6 0.0-2.0 TRENDS IN HB CONCENTRATION BY LESION CRC no in 3 round CRC yes in 3 round AA no in 3 round AA yes in 3 round AN no in 3 round AN yes in 3 round round 1 round 2 round 3 round 1 round 2 round 3 round 1 round 2 round 3
µd Hb/g 0 50 100 150 µd Hb/g 0 50 100 150 GROUP 1: DIFFERENCES IN HB CONCENTRATION BETWEEN THIRD ROUND AND FIRST ROUND BY LESION WOMEN Round 1 (µg Hb/g) Round 3-Round 1 (µg Hb/g) MEN Round 1 (µg Hb/g) Round 3-Round 1 (µg Hb/g) LESIONS IN ROUND 3 NO LESIONS IN ROUND 3 (24,995) CRC (27) AA (217) AN (244) LRA (149) 0.0 0.0-3.4 0.083 76.8 31.0-174.0 <0.001 1.8 0.0-5.5 <0.001 44.0 28.7-88.7 <0.001 1.6 0.0-5.3 <0.001 45.6 29.3-95.1 <0.001 0.2 0.0-2.2 <0.001 42.8 27.0-91.4 <0.001 0.0 0.0.-0.6 0.0 0.6-2.0 LESIONS IN ROUND 3 CRC (45) AA (437) AN (482) LRA (218) NO LESIONS IN ROUND 3 (18,738) 1.6 0.0-3.9 <0.001 121.2 48.2-366.1 <0.001 2.0 0.0-6.0 <0.001 46.8 29.1-105.1 <0.001 1.9 0.0-5.6 <0.001 49.4 29.5-112.5 <0.001 1.0 0.0-3.8 <0.001 41.8 26.1-75.7 <0.001 0.0 0.0-1.0 0.6 0.0-2.2 TRENDS IN HB CONCENTRATION IN ADVANCED NEOPLASIA WOMEN AN no in 3 round AN yes in 3 round MEN AN no in 3 round AN yes in 3 round round 1 round 2 round 3 round 1 round 2 round 3
GROUP 1: HB CONCENTRATION BY RANGES IN FIRST ROUND P< 0.001 P< 0.001 P< 0.001 BOTH SEX HB (µg Hb/g) IN ROUND 1 0.00-5.00 5.01-10.00 10.01-19.99 LESIONS IN CRC (72) 84.7% 6.9% 6 8.3% ROUND 3 AA (647) 72.5% 15.5% 12.1% AN (719) 73.7% 14.6% 11.7% LR (364) 83.8% 7.1% 9.1% NO LESIONS IN ROUND 3 (43,652) 94.3% 3.5% 2.3% WOMEN HB (µg Hb/g) IN ROUND 1 0.00-5.00 5.01-10.00 10.01-19.99 LESIONS IN CRC (27) 85.2% 7.4% 7.4% ROUND 3 AA (214) 72.9% 15.4% 11.7% AN (241) 74.3% 14.5% 11.2% LR (149) 86.6% 7.4% 6.0% NO LESIONS IN ROUND 3 (24,948) 95.1% 3.0% 1.9% MEN HB (µg Hb/g) IN ROUND 1 0.00-5.00 5.01-10.00 10.01-19.99 LESIONS IN CRC (45) 84.4% 6.7% 8.9% ROUND 3 AA (433) 72.3% 15.5% 12.2% AN (478) 73.4% 14.6% 11.9% LR (215) 81.9% 7.0% 11.2% NO LESIONS IN ROUND 3 (18,704) 93.3% 4% 2.7%
GROUP 1: DIFFERENCES IN HB CONCENTRATION BY CRC LOCALIZATION AND STAGE BOTH SEX Round 1 (µg Hb/g) Round 3-Round 1 (µg Hb/g) CRC RIGHT COLON (16) LEFT COLON (49) 1.3 0.0-4.3 58.2 30.6-147.2 0.536 0.6 0.0-3.5 114.4 42.7-394.3 0.244 BOTH SEX Round 1 (µg Hb/g) Round 3-Round 1 (µg Hb/g) CRC STAGE I-II (41) STAGE III-IV (28) 1.0 0.0-3.6 64.2 35.0-151.1 0.626 0.8 0.0-3.9 216.0 35.6-548.8 0.026
GROUP 2: DIFFERENCES IN HB CONCENTRATION BETWEEN SUCESSIVE AND PREVIOUS ROUND BY LESION BOTH SEX Round 1 (µg Hb/g) Round 2-Round 1 (µg Hb/g) LESIONS IN CRC ROUND 2 (417) AA (3,260) AN (3,677) LRA (1,799) NO LESIONS IN ROUND 2 (171,175) 2.2 0.0-8.0 <0.001 121.0 43.8-512.0 <0.001 2.2 0.0-7.6 <0.001 49.8 28.4-112.3 <0.001 2.2 0.0-7.8 <0.001 53.2 29.4-130.2 <0.001 0.4 0.0-3.4 <0.001 43.2 27.0-89.4 <0.001 0.0 0.0-0.4 0.0 0.4-2.0
GROUP 2: DIFFERENCES IN HB CONCENTRATION BETWEEN SUCESSIVE AND PREVIOUS ROUND BY LESION AND SEX WOMEN Round 1 (µg Hb/g) Round 2-Round 1 (µg Hb/g) LESIONS IN ROUND 2 CRC (147) 1.6 0.0-7.0 <0.001 96.9 40.3-392.4 <0.001 AA (1,017) AN (1,164) NO LESIONS IN ROUND 2 (94,986) 2.0 0.0-7.2 <0.001 48.8 27.2-103.0 <0.001 2.0 0.0-7.2 <0.001 50.8 28.6-118.2 <0.001 LRA (700) 0.2 0.0-2.9 <0.001 43.7 27.2-92.5 <0.001 0.0 0.0.-0.4 0.4 0.0-2.0 MEN Round 1 (µg Hb/g) Round 2-Round 1 (µg Hb/g) LESIONS IN ROUND 2 NO LESIONS IN ROUND 2 (76,189) CRC (270) 2.6 0.0-8.6 <0.001 140.2 45.8-555.0 <0.001 AA (2,228) AN (2,498) LRA (1,099) 2.4 0.0-8.0 <0.001 51.2 28.8-118.4 <0.001 2.4 0.0-8.0 <0.001 54.8 29.8-137.4 <0.001 0.6 0.0-3.8 <0.001 43.0 26.6-86.2 <0.001 0.0 0.0-0.6 0.4 0.0-2.0
GROUP 2: HB CONCENTRATION BY RANGES IN FIRST ROUND P< 0.001 BOTH SEX HB (µg Hb/g) IN ROUND 1 0.00-5.00 5.01-10.00 10.01-19.99 LESION IN CRC (417) 66.4% 14.9% 18.7% ROUND 2 AA (3,240) 66.5% 15.1% 18.4% AN (3,657) 66.5% 15.1% 18.4% LR (1,798) 80.1% 10.5% 9.5% NO LESION ROUND 2 (169,782) 93.9% 3.8% 2.3% P< 0.001 P< 0.001 WOMEN HB (µg Hb/g) IN ROUND 1 LESION IN ROUND 2 0.00-5.00 5.01-10.00 10.01-19.99 CRC (147) 70.7% 12.9% 16.3% AA (1,019) 69.4% 13.0% 17.7% AN (1,166) 69.6% 13.0% 17.5% LR (711) 81.2% 11.3% 7.65% NO LESION IN ROUND 2 (94,920) 94.5% 3.6% 2.0% MEN HB (µg Hb/g) IN ROUND 1 0.00-5.00 5.01-10.00 10.01-19.99 LESION IN ROUND 2 CRC (270) 64.1% 15.9% 20.0% AA (2,234) 65.6% 16.7% 17.8% AN (2,504) 65.4% 16.6% 18.0% LR (1,103) 79.1% 9.6% 11.3% NO LESION IN ROUND 2 (76,139) 92.7% 4.5% 2.8%
GROUP 2: DIFFERENCES IN HB CONCENTRATION BY CRC LOCALIZATION AND STAGE Round 1 (µg Hb/g) Round 2-Round 1 (µg Hb/g) BOTH SEX CRC RIGHT COLON (86) LEFT COLON (273) 1.2 0.0-5.4 85.3 39.5-687.8 0.033 2.8 0.0-9.4 146.4 50.3-516.5 0.272 BOTH SEX Round 1 (µg Hb/g) Round 2-Round 1 (µg Hb/g) CRC STAGE I-II (252) STAGE III-IV (115) 2.4 0.0-8.1 104.9 46.5-396.7 0.545 2.2 0.2-7.4 335.4 46.8-748.0 0.003
MESSAGE TO TAKE HOME There is no association between previous concentration of Hb and lesion detected in successive rounds. No special pattern was found that allows us to predict the development of Advanced Neoplasia after a negative result. The OR prediction found even their statistical significance in most cases has no clinical relevance No relevant differences were found by sex, age group, CRC stage and localization Intermittent bleeding could be the most important pattern Participation in screening is the most important key to detect lesions Previous bleeding (over 10µ Hb/g faeces) should be carefully considered In order to balance benefits and risks in Screening Programmes