European Digestive Cancer Days, Prague - 26. September 2017

Quantitative immunochemical tests: evidence on

accuracy and implementation considerations in the Czech

MUDr. Petr Kocna, CSc.

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QUANTITATIVE FIT FOR CRC SCREENING

Quantitative FIT are replacing traditional guaiac FOBT in

population screening programs for many reasons.

Quantitative FIT achieves 90% sensitivity for CRC detection and

is therefore at least 3 times more sensitive than guaiac test

Quantitative FIT needs to be optimised for population screening

with professional, epidemiological and economic aspects

Quantitative FIT offer much more than just FOBT+/FOBT-

results, and FIT cut-off could significantly modify the

screening programs

Quantitative FIT are developed over 20 years, and over the past

20 years there are 5189 publications in MEDLINE (09/2017)

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Shahidi N. Gentile L. Gondaraet L. al.: Can.J.Gastro.Hepatol. 2016

Correlating Quantitative Fecal Immunochemical Test Results with Neoplastic Findings

on Colonoscopy in a Population-Based Colorectal Cancer Screening Program.

0

10

20

30

40

50

60

10 - 15 15 - 20 20 - 40 40 - 100 > 100

adenoma low-risk

CRC - cancer

mg/g

Quantitative one FIT test (NS-Plus, Alfresa) with cut-off ≥ 10 μg/g

20 322 FIT positive subjects underwent colonoscopy.

Cut-off ≥ 10 μg/g with all adenoma detection exceeds national

recommendations and endoscopic sources need to be considered.

adenoma high-risk

Can.J.Gastro.Hepatol. - 06/2016

Pro

babili

ty

0 10 20 30 40 50 60 70 80 90 100 110 120 140 160

HEALTHY SUBJECTS

COLORECTAL

CANCER

4

ADENOMA

LOW-RISK

ADENOMA

HIGH-RISK

FIT ANALYSIS, FAECAL Hb CONCENTRATION, CUT-OFF

mg/g

cut-off FIT cut-off gFOBT

FIT 100 ng/ml

(20 mg/g)

FIT 50 ng/ml

(10 mg/g)

FIT 200 ng/ml

(40 mg/g)

Adenoma detection

approx. 30 %

CRC detection - 4,7

gFOBT positivity 3 - 5 %

CRC detection - 3,1

FIT positivity 8 - 11 %

Adenoma detection

approx. 50 %

CRC detection - 6,7

Effort to increase

Sensitivity and

Higher financial

efficiency

High

false positivity

Decrease

number

of colonoscopies

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Standardization of FIT analysis

Transferability of FIT analysis results

External quality control of FIT analysis

Accuracy and reliability of Hb analysis in stool

SETTING THE CUT-OFF VALUE FIT TEST - FIT OPTIMISATION

Determine sensitivity - rate of detected neoplasma /CRC

Determine specificity - the numbers of 'unnecessary' colonoscopies

Decide required capacity of GE centers and screening costs

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Fraser CG, Allison JE, Halloran SP, Young GP, Expert Working Group on Fecal

Immunochemical Tests for Hemoglobin, Colorectal Cancer Screening Committee

WEO. J Natl Cancer Inst 2012;104:810–14. A proposal to standardize reporting

units for fecal immunochemical tests for hemoglobin.

J Natl Cancer Inst - 04/2012

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Faecal immunochemical tests for Hb are replacing traditional guaiac faecal

occult blood tests in population screening programs for many reasons.

Many available faecal immunochemical test devices use a range of sampling

methods, differ with sampling methods, buffer volume and characteristics,

Hb stability and results are expressed by different way.

The current lack of consistency in units for Hb concentration is particularly

problematic because apparently similar Hb concentrations obtained with

different devices can lead to very different clinical interpretations.

Consistent adoption of an internationally accepted method for reporting results

would facilitate comparisons of outcomes from these tests. We propose a

simple strategy for reporting faecal Hb concentration

WEO

Expert Working Group (EWG)

Colorectal Cancer Screening Committee

(CRC SC)

IFCC

Scientific Division Working Group

Fecal Immunochemical Testing (WG-FIT)

First WG-FIT Meeting

Euromedlab Athens 14. June 2017

To harmonise and/or standardise analysis of haemoglobin

in faecal samples by immunochemistry (FIT)8

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J Lab Med Qual Assur - 10/2016

Chang-Ho Jeon and A-Jin Lee, J Lab Med Qual Assur 2016;38:120-128

Annual Report on the External Quality Assessment Scheme for

Urinalysis and Faecal Occult Blood Testing in Korea (2015)

External quality control in Korea - in 2015

EQA analysis was conducted 3x during the year - 1,250 participants

Qualitative tests - 569 participants (71%) - 9 different methods

Qualitative tests provide false-positive results

The success of the qualitative samples for negative sample was only 11%

Quantitative FIT test - 235 participants (29%) - 7 different analyzers

Totally different results depending on the technique used - in ng/ml

FIT REALIZED BY GENERAL PRACTITIONER IN CZECH - 2014

Král N., Seifert B., Korcová M.: Variability tests for occult blood used by general

practitioners in screening for colorectal cancer in the Czech Republic.

Gastroent Hepatol 2015 69(3): 255–258

g-FOBT 3%Laboratory FIT 7.5%

POCT FIT 23.5%

Qualitative FIT 66% - 13 different methods - rapid tests

QUESTIONNAIRE

FOR PRACTITIONERS

n = 522

10

11

0

25

50

75

100

125

150

175

200

225

250

ng/ml J Lab Med Qual Assur - 10/2016

Chang-Ho Jeon and A-Jin Lee, J Lab Med Qual Assur 2016;38:120-128

Annual Report on the External Quality Assessment Scheme for

Urinalysis and Faecal Occult Blood Testing in Korea (2015)

EQA Korea 2015

235 participants (29%)

7 different analyzers

Results in ng/ml

POSITIVE

SAMPLE

NEGATIVE

SAMPLE

cut-off

Eiken Eiken Eiken Alfresa Alfresa Kyowa Kyowa

Micro Diana Io NS-1000 NS-C HM-Jack HM-Jack Arc

Hb QUANTITATIVE ANALYSIS - FIT in CZECH REPUBLIC

External quality assessment Hb determination in the stool

started in January 2012, as a part of the national EQA

EQA programme provided by SEKK member of EQALM

accredited ISO/IEC 17043:2010

90 users in the Czech Republic

EQA in Czech Republic - 2 liquid samples, twice per year12

Data from cycle FOB 2016-01mg/g

FOB Gold analysis

sample A - 50 mg/g

sample B - 140 mg/g

OC-Sensor analysis

sample A - 30 mg/g

sample B - 80 mg/g

1,6x higher

April 2016 Eiken OC-Sensor

Sentinel FOBGold

CV - 8.10 %

CV - 8.85 %

Kocna P., Zima T., Budina M., Ichiyanagi T.: External Quality Assessment (EQA)

for Quantitative Fecal Blood in Stool (FIT). Biochimica Clinica, 2013, 37, 42313

FIT EXTERNAL QUALITY ASSESSMENT IN CZECH REPUBLIC

Toes-Zoutendijk E, van Leerdam ME, Dekker E et all. : Real-Time Monitoring of Results

During First Year of Dutch Colorectal Cancer Screening Program and Optimization

by Altering Fecal Immunochemical Test Cut-Off Levels.

Gastroenterology 2017;152:767–775

Gastroenterology - 03/2017

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Screening with cut-off 15 mg/g

according to OC-Sensor - Eiken study

Predicted positivity - 6.3 %

Screening done with the test

FOB Gold - Sentinel

FIT test positivity - 12.2 %

Cut-off has been modified to 47 mg/g

to effort positivity 6.3 %

Epidemiology of colorectal cancer: comparison of Czech regions

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Test positivity

FIT positivity in individual districts

could be significantly affected by the FIT method used

KT: 5,2

JH: 8,7

ZR: 8,8

KV: 5,9

ZN: 6,8

BR: 8,2

PB: 7,5

CB: 6,8

CK: 4,0

TR: 8,6PT: 9,2

OL: 6,4

JI: 6,8

TA: 6,1

TC: 9,2

SY: 6,9

PS: 6,8

SU: 5,9

BN: 11,6

PE: 6,8PI: 6,5

HB: 6,0

FM: 7,5

UO: 8,2

BV: 7,2

LT: 7,1

CL: 9,5

TU: 9,8

VS: 6,2

LN: 8,5

PJ: 6,3OP: 6,5

ZL: 5,1

ST: 8,6

HO: 6,4

MB: 6,6

CR: 6,7

RK: 8,0

UH: 6,7

NJ: 6,3

BK: 6,2

DO: 13,3

CV: 5,2

KH: 9,3

JC: 6,8

RA: 8,6

PA: 5,9

PR: 6,5

HK: 8,0NB: 6,0

KO: 7,6

JE: 4,9

SM: 6,9

BE: 8,6

BO: 6,9

LI: 6,1

CH: 7,7

VY: 8,5

DC: 7,0

NA: 7,8

PV: 6,9

KM: 6,6

SO: 4,6

KD: 6,5

ME: 7,8

PZ: 7,6

PH: 8,9

AX: 9,2

RO: 11,4

TP: 5,5MO: 6,4 JN: 9,7

UL: 7,0

KA: 4,6

BM: 7,6

OT: 5,9

PM: 7,2> 9,5

8,0-9,5

6,5-8,0

5,0-6,5

< 5,0< 5,05,0 – 6,56,5 – 8,08,0 – 9,5> 9,5

Total positivity (2016) : - 7.2 %Range between districts : 4,0 - 13,3 %

Májek O., Suchánek Š. Quality-assured immunochemical testing –

proposal for a pilot project in the Czech Republic

European Digestive Cancer Days, Prague - 26. September 2017

TAKE HOME MESSAGE

Efforts to change qualitative FIT to quantitative FIT

Efforts to change units from ng/ml to mg/g of stool

Standardization of FIT methods according to IFCC committee

Essential requirement for FIT external quality control

Personalized approach to FIT analysis of Hb in faeces

Screening programs modifications using FIT values

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