Colorectal Cancer Screening Methods Research Articles

Enhancing the Quality of Colonoscopy Through Split-Dose Bowel Preparation

Colonoscopy is a primary method for colorectal cancer screening, yet its efficacy as a screening tool is largely dependent on the quality of bowel preparation. An estimated 25% of patients undergoing colonoscopy have poor bowel preparations at the time of their procedure. There is empirical evidence to support that split-dose bowel preparations yield better bowel cleansing than day-prior bowel preparation regimens. The aim of this quality improvement project was to enhance the quality of colonoscopy at a large urban academic center through the use of split-dose bowel preparation. A total of 74 patients participated, with about half undergoing the current practice of day-prior bowel preparation and half undergoing the intervention of split-dose bowel preparation. Several procedural and patient outcome measures were collected and used for comparison to determine which bowel preparation was optimal for use in the practice setting. The findings revealed that split-dose bowel preparation resulted in better bowel cleansing, reduced recall intervals for the time to the next recommended colonoscopy, and improved patient tolerance, supporting its use in the practice setting to enhance the quality of colonoscopy.

Biomarkers of Coordinate Metabolic Reprogramming in Colorectal Tumors in Mice and Humans

There are no robust noninvasive methods for colorectal cancer screening and diagnosis. Metabolomic and gene expression analyses of urine and tissue samples from mice and humans were used to identify markers of colorectal carcinogenesis. Mass spectrometry-based metabolomic analysis of urine and tissues from wild-type C57BL/6J and Apc(Min/+) mice, as well as from mice with azoxymethane-induced tumors, was employed in tandem with gene expression analysis. Metabolic profiling was also performed on colon tumor and adjacent nontumor tissues from 39 patients. The effects of β-catenin activity on metabolic profiles were assessed in mice with colon-specific disruption of Apc. Thirteen markers were found in urine associated with development of colorectal tumors in Apc(Min/+) mice. Metabolites related to polyamine metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing mice with 100% accuracy, and also accurately identified mice with polyps. Changes in gene expression in tumor samples from mice revealed that derangement of metabolites were a reflection of coordinate metabolic reprogramming in tumor tissue. Similar changes in urinary metabolites were observed in mice with azoxymethane-induced tumors and in mice with colon-specific activation of β-catenin. The metabolic alterations indicated by markers in urine, therefore, appear to occur during early stages of tumorigenesis, when cancer cells are proliferating. In tissues from patients, tumors had stage-dependent increases in 17 metabolites associated with the same metabolic pathways identified in mice. Ten metabolites that were increased in tumor tissues, compared with nontumor tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine, xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric-dimethylarginine), were also increased in urine from tumor-bearing mice. Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of colorectal tumor samples from patients revealed pathways associated with derangement of specific metabolic pathways that are indicative of early-stage tumor development. These urine and tissue markers might be used in early detection of colorectal cancer.

Colonoscopy Quality is the Answer for the Emerging Issue of Interval Cancer.

Colonoscopy is currently regarded as the gold standard and preferred screening method for colorectal cancer (CRC). Recently, however, a limitation of colonoscopy in the prevention of CRCs has been identified, particularly in the right-sided colon, and the problem of so-called interval cancers has emerged. The prevalence of interval cancer is estimated to be between 4% and 8% of CRCs detected. Although the exact etiology of interval cancer remains unknown, factors implicated in the development of interval cancers include missed lesions at the time of colonoscopy, incomplete resection of previous neoplastic lesions, different tumor biology, and serrated pathway of carcinogenesis. However, recent evidence suggests that interval cancers are related to the training of the endoscopist and quality of the colonoscopy rather than tumor biology. Therefore, the importance of adequate training and continuous monitoring of the colonoscopy quality, which are amenable to improvement, cannot be overstated in order to prevent the risk of interval cancers. In this study, the current literature regarding the prevalence and potential factors related to interval cancers and colonoscopy quality-related issues are reviewed.

Not only hysterectomy but also cesarean section can predict incomplete flexible sigmoidoscopy among patients with prior abdominal or pelvic surgery

BackgroundFlexible sigmoidoscopy (FS) is a safe and effective method for colorectal cancer (CRC) screening. Several studies have demonstrated that individuals who have undergone surgery are at a greater risk of having incomplete FS. This study explored predictors of incomplete FS and reduced polyp detection rates for participants who had undergone abdominal or pelvic surgery. MethodsFrom January 2009 to December 2009, individuals participating in health examinations and who had undergone abdominal or pelvic surgery were invited to participate in this investigation. Four experienced gastroenterologists performed examinations using a 60-cm Olympus video sigmoidoscope. Factors associated with incomplete FS insertions and reduced polyp detection rates were analyzed using logistic regression models. ResultsOverall, 106 eligible individuals were analyzed, and 45 (42%) incomplete FS insertions were reviewed. Fifty participants (47%) had undergone pelvic surgery, and the other 56 (53%) had undergone abdominal surgery. Pelvic surgeries were cesarean section (25%) and hysterectomy (15%); appendectomy (36%) was the most common abdominal surgery. The main pathological FS findings were hemorrhoids (54%) and adenomatous polyps (18%). Multivariate analysis indicated that only prior pelvic surgery [odds ratio (OR), 3.54; p = 0.01] was an independent risk factor for incomplete FS insertion. Incomplete examinations were inversely related to adenomatous polyp detection rates (OR, 0.23; p = 0.03). ConclusionPrior pelvic surgery, particularly cesarean section and hysterectomy, is an independent factor for incomplete FS insertion in a selected adult population. In addition, incomplete FS can increase the risk of missing polyps, particularly in individuals who underwent pelvic surgery.

Flexible Sigmoidoscopy for Colorectal Cancer Screening in Canada

Flexible Sigmoidoscopy for Colorectal Cancer Screening in Canada

Fecal miR-106a Is a Useful Marker for Colorectal Cancer Patients with False-Negative Results in Immunochemical Fecal Occult Blood Test

Immunochemical fecal occult blood test (iFOBT) is widely used for colorectal cancer screening; however, its sensitivity is insufficient. We recently reported a fecal microRNA (miRNA) test (FmiRT) to detect colorectal cancer. In this study, we investigated a new colorectal cancer screening method combining iFOBT and FmiRT to improve the sensitivity compared with iFOBT alone. In total, 117 colorectal cancer patients and 107 healthy volunteers were enrolled. Ten-milligram fecal samples were collected and iFOBT was conducted. Fecal RNA was extracted from residuum of iFOBT and then the expression of 14 kinds of miRNA was analyzed for the FmiRT using real-time reverse transcription PCR. Levels of fecal miR-106a expression in iFOBT+ patients and iFOBT- patients were significantly higher than in healthy volunteers (P = 0.001). The sensitivity and specificity of FmiRT using miR-106a were 34.2% and 97.2%, and those of iFOBT were 60.7% and 98.1%, respectively. The overall sensitivity and specificity of the new screening method combining iFOBT and FmiRT were 70.9% and 96.3%, respectively. One quarter of colorectal cancer patients with false-negative iFOBT seemed to be true positive upon adding FmiRT using fecal miR-106a. Fecal miR-106a is a good molecular marker to identify colorectal cancer patients from among those with negative iFOBT results. FmiRT combined with iFOBT may improve the sensitivity to detect colorectal cancer. We have shown the usefulness of fecal miR-106a to detect the colorectal cancer patients among those with negative iFOBT results.

Clinical costs of colorectal cancer screening in 5 federally funded demonstration programs

The Centers for Disease Control and Prevention initiated the Colorectal Cancer Screening Demonstration Program (CRCSDP) to explore the feasibility of establishing a large-scale colorectal cancer (CRC) screening program for underserved populations in the United States. The authors of this report assessed the clinical costs incurred at each of the 5 participating sites during the demonstration period. By using data on payments to providers by each of the 5 CRCSDP sites, the authors estimated costs for specific clinical services and overall clinical costs for each of the 2 CRC screening methods used by the sites: colonoscopy and fecal occult blood test (FOBT). Among CRCSDP clients who were at average risk for CRC and for whom complete cost data were available, 2131 were screened by FOBT, and 1888 were screened by colonoscopy. The total average clinical cost per individual screened by FOBT (including costs for screening, diagnosis, initial surveillance, office visits, and associated clinical services averaged across all individuals who received screening FOBT) ranged from $48 in Nebraska to $149 in Greater Seattle. This compared with an average clinical cost per individual for all services related to the colonoscopy screening ranging from $654 in St. Louis to $1600 in Baltimore City. Variations in how sites contracted with providers and in the services provided through CRCSDP affected the cost of clinical services and the complexity of collecting cost data. Health officials may find these data useful in program planning and budgeting.

Electronic Cleansing for 24-H Limited Bowel Preparation CT Colonography Using Principal Curvature Flow

CT colonography (CTC) is one of the recommended methods for colorectal cancer screening. The subject's preparation is one of the most burdensome aspects of CTC with a cathartic bowel preparation. Tagging of the bowel content with an oral contrast medium facilitates CTC with limited bowel preparation. Unfortunately, such preparations adversely affect the 3-D image quality. Thus far, data acquired after very limited bowel preparation were evaluated with a 2-D reading strategy only. Existing cleansing algorithms do not work sufficiently well to allow a primary 3-D reading strategy. We developed an electronic cleansing algorithm, aimed to realize optimal 3-D image quality for low-dose CTC with 24-h limited bowel preparation. The method employs a principal curvature flow algorithm to remove heterogeneities within poorly tagged fecal residue. In addition, a pattern recognition-based approach is used to prevent polyp-like protrusions on the colon surface from being removed by the method. Two experts independently evaluated 40 CTC cases by means of a primary 2-D approach without involvement of electronic cleansing as well as by a primary 3-D method after electronic cleansing. The data contained four variations of 24-h limited bowel preparation and was based on a low radiation dose scanning protocol. The sensitivity for lesions ≥ 6 mm was significantly higher for the primary 3-D reading strategy (84%) than for the primary 2-D reading strategy (68%) (p = 0.031). The reading time was increased from 5:39 min (2-D) to 7:09 min (3-D) (p = 0.005); the readers' confidence was reduced from 2.3 (2-D) to 2.1 (3-D) ( p = 0.013) on a three-point Likert scale. Polyp conspicuity for cleansed submerged lesions was similar to not submerged lesions (p = 0.06). To our knowledge, this study is the first to describe and clinically validate an electronic cleansing algorithm that facilitates low-dose CTC with 24-h limited bowel preparation.

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

BackgroundAs screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in...

Blood-based screening for methylation changes in colorectal cancer patients using novel nanotechnologies.

384 Background: Identification of blood-based biomarkers for cancer screening is essential in order to develop novel and minimally invasive methods for colorectal cancer screening. Our lab has successfully applied a novel nanotechnology that allows us to detect and amplify a single tumor DNA fragment in a plasma sample. This DNA is tested for methylation of several genes including TFPI2 which has shown to be highly sensitive and specific for the detection colorectal cancer in stool. Methods: Whole blood was obtained from 18 colorectal cancer patients and plasma was isolated. Plasma was processed using Methylation On Beads nanotechnology (MOB) and bisulfate treated. Methylation status was determined via quantitative PCR method. Results: Two genes, TFPI2 and IGFBP3, were detected with a high sensitivity. TFPI2, demonstrated a methylation frequency of 94.4%, which is concordant with the TFPI2 methylation frequency of 99% in primary colorectal cancer tissues. IGFBP3 showed the methylation frequency of 61.1%, which corresponds with the methylation frequency of 52% in retrospective colorectal cancer tissues in previous studies. Quantification using standard curves indicated a single copy level of DNA found in plasma. Conclusions: Blood-based screening is challenging due to extremely low quantities of circulating DNA in blood. Utilizing a novel nanotechnology that detects DNA at a single copy level, the methylation changes in colorectal cancer were successfully detected in plasmas at similar frequencies as in tissue samples. This study has demonstrated the feasablility and applicability to blood-based screening. Future studies will focus on improving the sensitivity and determining the specificity of this method.

Colorectal cancer screening in an equal access healthcare system.

Introduction: The military health system (MHS) a unique setting to analyze implementation programs as well as outcomes for colorectal cancer (CRC). Here we look at the efficacy of different CRC screening methods, attributes and results within the MHS, and current barriers to increase compliance.Materials and Methods: A literature search was conducted utilizing PubMed and the Cochrane library. Key-word combinations included colorectal cancer screening, racial disparity, risk factors, colorectal cancer, screening modalities, and randomized control trials. Directed searches were also performed of embedded references.Results: Despite screening guidelines from several national organizations, extensive barriers to widespread screening remain, especially for minority populations. These barriers are diverse, ranging from education and access problems to personal beliefs. Screening rates in MHS have been reported to be generally higher at 71% compared to national averages of 50-65%.Conclusion: CRC screening can be highly effective at improving detection of both pre-malignant and early cancers. Improved patient education and directed efforts are needed to improve CRC screening both nationally and within the MHS.

Participation and Barriers to Colorectal Cancer Screening in Malaysia

In Malaysia, colorectal cancer is the most common cancer in males and the third most common in females. Mortality due to colorectal cancer can be effectively reduced with early diagnosis. This study was designed to look into colorectal cancer screening participation and its barriers among average risk individuals in Malaysia. A cross sectional study was conducted from August 2009 till April 2010 involving average risk individuals from 44 primary care clinics in West Malaysia. Each individual was asked whether they have performed any of the colorectal cancer screening methods in the past five years. The barrier questions had three domains: patient factors, test factors and health care provider factors. Descriptive analysis was achieved using Statistical Program for Social Sciences (SPSS) version 12.0. A total of 1,905 average risk individuals responded making a response rate of 93.8%. Only 13 (0.7%) respondents had undergone any of the colorectal cancer screening methods in the past five years. The main patient and test factors for not participating were embarrassment (35.2%) and feeling uncomfortable (30.0%), respectively. There were 11.2% of respondents who never received any advice to do screening. The main reason for them to undergo screening was being advised by health care providers (84.6%). The study showed that participation in colorectal cancer screening in Malaysia is extremely low and multiple factors contribute to this situation. Given the importance of the disease, efforts should be made to increase colorectal cancer screening activities in Malaysia.

Performance of Repeated Fecal Immunochemical Testing for Colorectal Cancer Screening

The fecal immunochemical test (FIT) is receiving increasing attention as an effective method of colorectal cancer screening. However, few data are

Abstract 4448: Fecal miRNA test using microRNA expressions of exfoliated colonocytes for colorectalcancer screening

Abstract Background & Aims: To reduce the mortality rate of several cancers, the development of a screening test is needed. We have been developing new screening methods for colorectal cancer (CRC) by applying molecular biological tools to exfoliated colonocytes. In the last few years especially, we have reported the fecal RNA test including the CRC-related gene expression analysis. Here, we investigated the potential of a fecal miRNA test for the early detection of CRC. Methods: CRC patients (n = 299) and healthy volunteers (n = 116) with no abnormalities detected by screening colonoscopy were enrolled in this case control study. The miRNA expressions in the colonocytes of CRC patients (n = 47) and healthy volunteers (n = 35) were analyzed in the training study and the miRNA expressions in the colonocytes of CRC patients (n = 252) and healthy volunteers (n = 81) were validated in the validation study. First, CRC related oncogenic miRNAs for CRC detection were selected by TaqMan MicroRNA Array v3.0 (corresponded to miRBase release 14). Next, the expressions of the most suitable oncogenic miRNAs were analyzed by quantitative real-time PCR in the training study. Lastly, the sensitivity and specificity of fecal miRNA test was validated by quantitative real-time PCR in the validation study. Results: According to the results of miRNA array, 20 miRNAs were selected as candidate of miRNA analysis. In the training study, significant differences in the relative expression level of miR-17, -18a, -19a, -19b, -20a, -92a, -106a, -135a, -135b, and -146a were observed between the CRC patients and the healthy volunteers (P < 0.01). On the other hand, there was no significant difference in the relative expression level of miR-21, -183, -223, and -454* between the CRC patients and the healthy volunteers (P > 0.1) AUC of ROC curve using miR-17, -18a, -19a, -19b, -20a, -92a, -106a, -135b, and -146a were more than 0.7. The overall sensitivity and specificity in the training study using these miRNAs were 70.2% (33/47) and 74.3% (26/35), respectively. The overall sensitivity and specificity in the validation study were 67.5% (170/252) and 75.3% (61/81), respectively. Conclusions: We selected the suitable miRNAs for CRC detection in exfoliated colonocytes. Fecal miRNA test may be useful for CRC screening. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4448. doi:1538-7445.AM2012-4448

444 Is EGD Necessary in Patients With Positive Fecal Occult Blood Test and Negative Colonoscopy?

Fecal occult blood test (FOBT) is known to be a cheap and effective screening method for colorectal cancer (CRC), and total colonoscopy is warranted in a patient with positive FOBT. False positives regarding CRC detection are common, and caused by testing methods or upper gastrointestinal (GI) occult bleeding. Gastric cancer and peptic ulcers are relatively common in some countries, and it is important to establish management plan in patients with positive FOBT and negative colonoscopy. We aimed to investigate upper GI condition confirmed by endoscopy in positive FOBT patients without advanced colorectal neoplasia, hemorrhoid or colitis.

Mo1237 Colonoscopy Bowel Preparation Quality and Follow-Up in a Racially Diverse, Urban Patient Population

Colonoscopy is a preferred screening method for colorectal cancer (CRC). Poor bowel preparation leads to inadequate studies and shorter surveillance intervals. Previous studies have identified risk factors for inadequate preparation including age, male gender, and afternoon procedure time. However, studies have not included sufficient African Americans (AAs) nor considered recommendations and quality of follow-up exams. Our aim was to determine prevalence of inadequate bowel preparation on initial and follow-up colonoscopy in a large, racially diverse patient population.

442 Technological Assistance of Cap-Assisted Chromoendoscopy Enhances the Detection Rates of Both Colorectal Adenoma and Proximal Serrated Polyp in an Average-Risk Screening Population: Preliminary Results of a Multi-Center Randomized Controlled Trial

Technological Assistance of Cap-Assisted Chromoendoscopy Enhances the Detection Rates of Both Colorectal Adenoma and Proximal Serrated Polyp in an Average-Risk Screening Population: Preliminary Results of a Multi-Center Randomized Controlled Trial Hyun-Soo Kim*, Hong Jun Park, Chan Sik Won, Hyo Keun Jeon, Dongil Park, Jae Myung Cha, Seun-Ja Park, Hwang Choi, Jeong Eun Shin, Chang Soo Eun, Jin-Oh Kim, Hyun Gun Kim, Seong-Eun Kim, Cheol Hee Park, Tae Il Kim, Sung Noh Hong, Dong-Hoon Yang, Byung Chang Kim, Byungho Nam Yonsei Univ. Wonju College of Medicine, Wonju, Republic of Korea; Sungkyunkwan University College of Medicine, Seoul, Republic of Korea; KyungHee University College of Medicine, Hanam, Republic of Korea; Kosin University College of Medicine, Busan, Republic of Korea; The Catholic University of Korea College of Medicine, Incheon, Republic of Korea; Dankook University College of Medicine, Cheonan, Republic of Korea; Hanyang University College of Medicine, Guri, Republic of Korea; Soonchunhyang University College of Medicine, Seoul, Republic of Korea; Ewha Womans University School of Medicine, Seoul, Republic of Korea; Hallym University College of Medicine, Anyang, Republic of Korea; Yonsei University College of Medicine, Seoul, Republic of Korea; Konkuk University School of Medicine, Seoul, Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of Korea; National Cancer Center, Goyang, Republic of Korea Background/Aim: There is growing evidence that a transparent cap or chromoendoscopy improve detection of colorectal polyps. However, the combined method of these two technologies has not been proven for colorectal polyp or adenoma detection rate. In this multicenter prospective randomized trial, we examined whether cap-assisted chromoendoscopy (CAP-ACE) enhances colorectal adenoma detection rate especially in the proximal colon. Methods: From March 2010 to October 2011, 1,202 asymptomatic average-risk subjects who underwent the first screening colonoscopy in an age of 45 to 75 were enrolled at 14 hospitals. Eighteen expert colonoscopists (more than 5,000 procedures) have performed procedures. Subjects were randomly allocated to CAP-ACE group and regular colonoscopy (RC) group. We prospectively compared insertion and withdrawal time, polyp detection rate (PDR), adenoma detection rate (ADR), and proximal serrated polyp detection rate (PSPDR) between the two groups. Results: A total of 1,202 subjects were enrolled; 598 CAP-ACEs and 604 RCs were performed. Overall PDR and ADR were 60.3% and 47.6%. A total of 52 advanced lesions were found including 16 tubulovillous adenomas, 2 villous adenomas, 13 high grade dysplasias, 11 intramucosal cancers and 10 invasive cancers. The time to cecal intubation (4.8 vs. 4.8 min, p 0.902) was not different between the groups but withdrawal time was prolonged in CAP-ACE group for indigocarmine solution spray and suction (10.5 vs. 8.7 min, p 0.001). Compared to RC, CAP-ACE did increase PDR (65.9% vs. 54.8%, p 0.001) and ADR (51.8% vs. 45.5%, p 0.033) significantly. In particular, this technological assistance of CAP-ACE even in experts significantly enhanced the proximal adenoma detection rate (34.8% vs. 28.8%, p 0.030) as well as PSPDR (10.5% vs. 6.1%, p 0.006). However, advanced lesions (CAPACE 26/598 (4.3%) vs. RC 26/604 (4.3%), p 0.99) including cancers were equally found between groups. Conclusion: Technological assistance of CAP-ACE enhances not only PDR but also ADR, especially in the proximal colon. These results suggest that CAP-ACE technology provide a potential solution for overcoming the limited effectiveness of colonoscopy in the proximal colon and should be considered as the preferred, high standard colorectal cancer screening method for the average-risk screening population.

Novel molecular screening approaches in colorectal cancer

Traditional methods for colorectal cancer (CRC) screening have reduced rates of malignancy and death; however, low compliance and morbidities associated with invasive techniques have encouraged efforts for establishing equally effective, less invasive novel screening approaches. We review the current state of novel screening approaches in CRC to include CT colonography, fecal DNA, DNA methylation, micro-RNA, and protein and molecular markers.

Interval colorectal cancer despite screening colonoscopy: A single-center experience.

401 Background: Colonoscopy is recommended as the primary screening method for colorectal cancer (CRC) and polypectomy is considered effective for preventing cancer. CRCs which occur within 5 years of screening colonoscopy are defined as interval cancer. Despite regular colonoscopy and complete polypectomy interval colorectal cancer may occur. Methods: All patients undergoing a colonoscopy were recorded in a colonoscopy registry, all CRC-patients who underwent colectomy were recorded in a surgery registry and all patients with newly diagnosed CRC were recorded in a tumor registry at the Klinikum Wels-Grieskirchen. In this retrospective analysis all patients with newly diagnosed CRC since the year 2000 were evaluated if a screening colonoscopy was done before the diagnosis of CRC at our institution. Results: Overall, 1.102 patients with CRC were evaluated. 939 patients underwent tumorectomy/colectomy at our department of surgery. In 65.8% (n=725) CRC was detected by colonoscopy at our institution and 85 out of these patients had a previous screening colonoscopy (range 14-176 months, median 55 months) at our institution. Interval cancers, which occur within 5 years since screening colonoscopy, were detected in 45 patients. Six patients could be identified with complete negative colonoscopy, 2 patients had inadequate bowel preparation, in 7 patients colonoscopy was not complete because of technical problems, 26 patients had a history of colorectal adenomas and 4 patients had inflammatory bowel disease. In 16 out of 26 patients with adenomas a CRC was detected distant from the side of the previous polypectomy. Conclusions: More emphasis and short-term control of incomplete and inadequately prepared colonoscopies, as well as a re-call system for post-polypectomy controls could reduce the number of so called interval CRSs.

A novel, cost-effective strategy for the screening of colorectal cancer with higher patient compliance.

407 Background: Routine screening methods for colorectal cancer (CRC) have poor patient compliance and low sensitivity for early stages. The sensitivity rates are 19, 71, 76, and 83% for Fecal Occult Blood test (FOBT), stool DNA test, colonoscopy/sigmoidoscopy, and double-contrast barium enema; respectively. Biological markers have also been tested including CEA (sensitivity of 38.7%); however, its utility in CRC screening is limited due to low sensitivity. Onko-Sure is an FDA-cleared blood test for monitoring of CRC treatment/recurrence. It measures the accumulation of Fibrin/Fibrinogen Degradation products in the serum using anti-DR-70 antibody. The objective was to determine whether DR-70 and CEA combination can improve the sensitivity such that it can be used as a cost-effective alternative to current screening methods yet with a higher patient compliance. Methods: A total of 564 serum samples were retrospectively obtained from a serum bank in two arms: confirmed healthy control (n=298) and biopsy-confirmed CRC (n=266) groups. The samples were tested for DR-70 and CEA. Results: The results showed sensitivity of 58.2% and specificity of 59.83% for DR-70 and CEA combined. The sensitivity for the combined test was 55.5% higher than that of CEA alone. A consistent improvement of sensitivity for the combined usage relative to CEA alone was observed with an increase of 73%, 108%, 58% and 18% in CRC stage I, II, III and IV; respectively. The sensitivity of the combined test was 48%, 47%, 57% and 98% for stages I, II, III and IV. Conclusions: Combining DR-70 and CEA tests showed a significant clinical advantage in CRC screening over using each marker alone. The sensitivity improvement was highest for stages I/II, which has important implications in patient treatment options, prognosis and survival rate due to this early detection. With a 3 times higher sensitivity for early stage CRC compared to using FOBT, this approach should improve the CRC early stage diagnosis. Such early stage detection is less likely using routine approaches for CRC screening because of low sensitivity and low patient compliance.