Higher fecal immunochemical test cutoff levels: lower positivity rates but still acceptable detection rates for early-stage colorectal cancers.
BACKGROUND
Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC).


METHODS
Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL.


RESULTS
In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from ≥ 50 to ≥ 200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively.


CONCLUSIONS
Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present.


CONCLUSIONS
Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers.
Department of Gastroenterology and Hepatology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, the Netherlands. js.terhaar@vumc.nl
Jochim S
JS
Terhaar sive Droste
Frank A
FA
Oort
René W M
RW
van der Hulst
Henk A
HA
van Heukelem
Ruud J L F
RJ
Loffeld
Sietze T
ST
van Turenhout
Ilhame
I
Ben Larbi
Shannon L
SL
Kanis
Maarten
M
Neerincx
Mirre
M
Räkers
Veerle M H
VM
Coupé
Anneke A
AA
Bouman
Gerrit A
GA
Meijer
Chris J J
CJ
Mulder
D000236:Adenoma / Q000175:diagnosis* / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000517:prevention & control; D055088:Early Detection of Cancer; D005243:Feces / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015996:Survival Rate