Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers.
BACKGROUND
Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood. Preliminary results show that protein, genetic, epigenetic, and metabolomic components may be valuable in blood-based screening concepts, particularly when combinations of the various components appear to lead to significant improvements.


OBJECTIVE
The protocol described in this paper focuses on the validation of concepts based on biomarkers in blood in a major population screened by FIT.


METHODS
In Part 1, participants will be identified and included through the Danish CRC Screening Program comprising initial FIT and subsequent colonoscopy to those with a positive result. Blood samples will be collected from 8000 FIT-positive participants, who are offered subsequent colonoscopy. Findings and interventions at colonoscopy together with personal data including co-morbidity will be recorded. Blood samples and data will also be collected from 6000 arbitrarily chosen participants with negative FIT. In Part 2, blood samples and data will be collected from 30,000 FIT-negative participants three times within 4 years. The blood samples will be analyzed using various in-house and commercially available manual and automated analysis platforms.


RESULTS
We anticipate Part 1 to terminate late August 2016 and Part 2 to terminate late September 2022. The results from Parts 1 and 2 will be presented within 12 to 18 months from termination.


CONCLUSIONS
The purpose of this study is to improve the efficacy of identifying participants with neoplastic bowel lesions, to identify false negative participants, to identify participants at risk of interval neoplastic lesions, to improve the compliance in screening sessions, and to establish guidelines for out-patient follow-up of at-risk participants based on combinations of blood-based biomarkers.
Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark. lras2905@gmail.com.
Louise
http://orcid.org/0000-0003-4576-7101
L
Rasmussen
Michael
http://orcid.org/0000-0002-8142-9030
M
Wilhelmsen
Ib Jarle
http://orcid.org/0000-0002-3017-7195
IJ
Christensen
Jens
http://orcid.org/0000-0001-7632-0842
J
Andersen
Lars Nannestad
http://orcid.org/0000-0001-7465-5374
LN
Jørgensen
Morten
http://orcid.org/0000-0002-2560-1772
M
Rasmussen
Jakob W
http://orcid.org/0000-0002-9318-4149
JW
Hendel
Mogens R
http://orcid.org/0000-0001-7997-5430
MR
Madsen
Jesper
http://orcid.org/0000-0001-7122-9687
J
Vilandt
Thore
http://orcid.org/0000-0002-2085-5183
T
Hillig
Michael
http://orcid.org/0000-0002-4012-7888
M
Klærke
Anna-Marie Bloch
http://orcid.org/0000-0002-3398-3977
AM
Münster
Lars M
http://orcid.org/0000-0001-7042-4835
LM
Andersen
Berit
http://orcid.org/0000-0003-4074-6504
B
Andersen
Nete
http://orcid.org/0000-0002-2462-9490
N
Hornung
Erland J
http://orcid.org/0000-0002-6686-3971
EJ
Erlandsen
Ali
http://orcid.org/0000-0002-5380-1077
A
Khalid
Hans Jørgen
http://orcid.org/0000-0001-5203-8148
HJ
Nielsen
colorectal neoplasms; early detection of cancer; epigenomics; genomics; metabolomics; proteomics; transcriptome