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Wang SY, Dong XT, Yuan Z, Jin LX, Gao WF, Han YK, Ni KM, Liu ZC, Wang JY, Wei XM, Su XM, Peng X, Zhang CZ. Factors associated with false fecal immunochemical test results in colorectal cancer screening. World J Gastrointest Oncol 2025; 17:101487. [DOI: 10.4251/wjgo.v17.i4.101487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/10/2024] [Accepted: 01/22/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Certain subgroups are at an increased risk of false fecal immunochemical test (FIT) results; however, related studies are limited, and the available evidence is conflicting.
AIM To evaluate factors associated with false-positive and false-negative FIT results.
METHODS This retrospective study was based on the database of the Tianjin Colorectal Cancer Screening Program from 2012 to 2020. A total of 4129947 residents aged 40-74 years completed at least one FIT. Of these, 24890 asymptomatic participants who underwent colonoscopy examinations and completed lifestyle questionnaires were included in the analysis. Multivariable logistic regression was performed to identify the factors associated with false FIT results.
RESULTS Among the overall screening population, 88687 (2.15%) participants tested positive for FIT. The sensitivity, specificity, positive predictive value, and negative predictive value of FIT for advanced neoplasms were 58.2%, 44.8%, 9.7%, and 91.3%, respectively. Older age, female sex, smoking, alcohol consumption, higher body mass index, and hemorrhoids were significantly associated with increased odds of false-positive and lower odds of false-negative FIT results. Moreover, features of high-grade dysplasia or villous for advanced adenoma and the presence of cancer were also associated with lower odds of false-negative results, while irregular exercise and diverticulum were associated with higher odds of false-positive results.
CONCLUSION FIT results may be inaccurate in certain subgroups. Our results provide important evidence for further individualization of screening strategies.
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Affiliation(s)
- Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Xue-Tao Dong
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300121, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Lei-Xin Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Wei-Feng Gao
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - You-Kui Han
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Ke-Min Ni
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Zhao-Ce Liu
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Jun-Ying Wang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Xiao-Meng Wei
- Hospital Infection Management Division, Tianjin Union Medical Center, Tianjin 300121, China
| | - Xiao-Min Su
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Xi Peng
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Chun-Ze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
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Harlass M, Dalmat RR, Chubak J, van den Puttelaar R, Udaltsova N, Corley DA, Jensen CD, Collier N, Ozik J, Lansdorp-Vogelaar I, Meester RGS. Optimal Stopping Ages for Colorectal Cancer Screening. JAMA Netw Open 2024; 7:e2451715. [PMID: 39699893 DOI: 10.1001/jamanetworkopen.2024.51715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2024] Open
Abstract
Importance Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient's sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk. Objective To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective. Design, Setting, and Participants This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis-Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024. Exposures CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results. Main Outcomes and Measures The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $100 000 per QALYG, was evaluated. Results The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT. Conclusions and Relevance In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.
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Affiliation(s)
- Matthias Harlass
- Department of Public Health, Erasmus University Medical Center, Rotterdam, South Holland, the Netherlands
| | - Ronit R Dalmat
- Department of Global Health, University of Washington, Seattle
| | - Jessica Chubak
- Department of Epidemiology, University of Washington, Seattle
- Kaiser Permanente Washington Health Research Institute, Seattle
| | - Rosita van den Puttelaar
- Department of Public Health, Erasmus University Medical Center, Rotterdam, South Holland, the Netherlands
| | - Natalia Udaltsova
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Douglas A Corley
- Division of Research, Kaiser Permanente Northern California, Oakland
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California
| | | | - Nicholson Collier
- Decision and Infrastructure Sciences, Argonne National Laboratory, Lemont, Illinois
- Consortium for Advanced Science and Engineering, The University of Chicago, Chicago, Illinois
| | - Jonathan Ozik
- Decision and Infrastructure Sciences, Argonne National Laboratory, Lemont, Illinois
- Consortium for Advanced Science and Engineering, The University of Chicago, Chicago, Illinois
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus University Medical Center, Rotterdam, South Holland, the Netherlands
| | - Reinier G S Meester
- Department of Public Health, Erasmus University Medical Center, Rotterdam, South Holland, the Netherlands
- Health Economics and Outcomes Research, Freenome Holdings Inc, South San Francisco, California
- Stanford University School of Medicine, Stanford, California
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Abu-Freha N, Guterman R, Elhayany R, Cohen DL, Munteanu D, Dizengof V, Yitzhak A, Hazzan R, Fich A. Sex Differences in Colonoscopy Indications and Findings: Results from a Large Multicenter Database. J Womens Health (Larchmt) 2024; 33:1442-1448. [PMID: 39445639 DOI: 10.1089/jwh.2024.0301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024] Open
Abstract
Background: Sex-based differences are common among diseases. We aimed to investigate the differences in colonoscopy indications and its findings between males and females. Methods: A large, multi-center, cross-sectional, retrospective study included all colonoscopies performed between 2016 and 2021 in seven endoscopy departments. The indications and findings of the procedures were compared between males and females. Results: A total of 151,411 (52.6%) women and 136,519 (47.4%) men were included, aged 56.54 ± 12.9 years and 56.59 ± 12.7. Cecal intubation was similar (95.6% vs 95.5%, p = 0.251). More females had excellent or good bowel preparation compared to males (71.4% vs 65.6%). Colonoscopy due to abdominal pain, constipation, diarrhea, and anemia was higher in females compared to males (15% vs 9.9%, 3.9% vs 2.2%, and 7.6% vs 4.9%, p < 0.001, respectively), while positive FOBT, rectal bleeding and post-polypectomy surveillance and screening were more common indications among males (9.5% vs 7.8%, 10.7% vs 7.8%, and 10.8% vs 7.1%, respectively). On colonoscopy, males were found to have significantly higher colorectal cancer and polyps (0.5% vs 0.4% and 35.1% vs 24.6%). Polyp detection rates were lower in females across all indications, whereas diverticulosis rates were higher in males. However, a clinically significant difference regarding diverticulosis was observed only in patients with anemia as the indication. Conclusions: Notable differences exist between males and females in terms of the indications and findings on colonoscopy. This highlights the need for identifying the factors contributing to these differences and the developing sex-specific approaches for the diagnosis and management of gastrointestinal diseases.
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Affiliation(s)
- Naim Abu-Freha
- Assuta Hospital, Beer-Sheva, Israel
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | | | | | - Daniel L Cohen
- Shamir (Assaf Harofeh) Medical Center, The Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Zerifin, Israel
| | | | | | | | - Rawi Hazzan
- Assuta centers, gastroenterology institute, Haifa, Israel
- Azrieli Faculty of Medicine, Bar-Ilan university, Safed, Israel
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Boulbadaoui A, Rashid MU, Nair N, Mohamed G, Poh S, Britton I, Balasubramaniam R, Gaunt A, Varghese P. Straight-to-Test Pathway in Faecal Immunochemical Testing (FIT)-Negative Patients: A Cost-Effective Approach. Cureus 2024; 16:e73464. [PMID: 39529920 PMCID: PMC11554240 DOI: 10.7759/cureus.73464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2024] [Indexed: 11/16/2024] Open
Abstract
INTRODUCTION Colorectal cancer (CRC) is the fourth most common malignancy in the UK and represents a high-volume diagnostic and clinical burden on the National Health Service (NHS). To maximise the use of limited diagnostic resources and increase efficiency, the colorectal services at University Hospitals North Midlands Trust (UHNM) developed the triage-to-test (TTT) service with risk stratification for diagnostic testing in patients with suspected colorectal cancer using faecal immunochemical testing (FIT) result. Our retrospective cohort study looked at the pick-up rate of colorectal cancer (CRC) and non-colorectal cancer (non-CRC) in FIT-negative patients. METHODS The study was a retrospective review of all symptomatic patients over 18 years of age who had undergone FIT testing in the community between 1 November 2021 and 11 February 2022 and who were referred directly to the UHNM colorectal pathway from primary care (n=2,374). FIT negativity was set at <9.9 μg/g of faeces, as per the National Institute for Health and Care Excellence (NICE) DG30 guidelines. Patients were investigated and risk stratified in accordance with their FIT result and presenting symptoms. RESULTS About 61.5% of patients referred were FIT negative (n=1,459) and 38.5% were FIT positive (n=915). Of those FIT-negative patients, 82 were excluded as their clinical outcomes were pending at the time of analysis. FIT positivity conferred a greater likelihood of colorectal cancer when compared with FIT-negative patients (p<0.0001). FIT-negative patients were most likely to have no significant pathology (32.5%, n=474). Incidence of colorectal cancer in the FIT-negative group was 0.5% (n=7) compared with 9.8% (n=89) in the FIT-positive group (odds ratio: 5.252, 95% CI: 4.012-6.875). Within the FIT-negative cohort, five patients were diagnosed with rectal cancer, one proximal descending colon cancer and one caecal cancer. CONCLUSION The use of a FIT-negative TTT pathway ensures that any symptomatic patients presenting with red flag symptoms can be investigated appropriately. It also provides reassurance to clinicians who have an ethical duty to investigate patients in whom they suspect sinister pathology. Moreover, a triage-to-Test pathway reduces outpatient capacity burden on healthcare trusts as they may send patients directly for investigation.
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Affiliation(s)
- Amal Boulbadaoui
- Colorectal Surgery, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | - Muhammad Umair Rashid
- General Surgery, University Hospitals of Derby and Burton NHS Foundation Trust, Stoke-on-Trent, GBR
| | - Nandu Nair
- Colorectal Surgery, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | - Guleed Mohamed
- Urology, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | - Shawn Poh
- Colorectal Surgery, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | - Ingrid Britton
- Radiology, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | | | - Anne Gaunt
- Colorectal Surgery, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
| | - Philip Varghese
- Colorectal Surgery, University Hospitals of North Midlands (UHNM) NHS Trust, Stoke-on-Trent, GBR
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Bonhof CS, de Rooij BH, Schoormans D, Wasowicz DK, Vreugdenhil G, Mols F. Sex differences in health-related quality of life and psychological distress among colorectal cancer patients: a 2-year longitudinal study. J Cancer Surviv 2024:10.1007/s11764-024-01616-0. [PMID: 38789659 DOI: 10.1007/s11764-024-01616-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 05/11/2024] [Indexed: 05/26/2024]
Abstract
PURPOSE While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up. METHODS Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 334) completed questions on HRQoL (EORTC QLQ-C30) and psychological distress (HADS) before initial treatment (baseline), 4 weeks after surgery, and at 1 and 2 years after diagnosis. Also, HRQoL and psychological distress were assessed in a sex- and age-matched reference population. RESULTS When directly comparing female (N = 126, 38%) and male (N = 208, 62%) CRC patients, female patients reported significantly worse HRQoL, such as more insomnia at baseline, worse physical and role functioning 4 weeks after surgery, more diarrhea at 1 year, and more pain and constipation at 2-year follow-up. However, a comparison with the reference population revealed larger differences between patients and reference in males than in females. For example, at 1- and 2-year follow-up, male patients reported significantly worse cognitive and social functioning, more insomnia, and more anxiety compared with a reference population. CONCLUSIONS Especially male CRC patients reported worse HRQoL and more psychological distress when compared with a reference population. IMPLICATIONS FOR CANCER SURVIVORS Knowledge of sex-specific differences in HRQoL and psychological distress among CRC patients may help healthcare providers anticipate and appropriately address patients' unique healthcare needs.
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Affiliation(s)
- Cynthia S Bonhof
- CoRPS-Center of Research on Psychological Disorders and Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Belle H de Rooij
- CoRPS-Center of Research on Psychological Disorders and Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Dounya Schoormans
- CoRPS-Center of Research on Psychological Disorders and Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Dareczka K Wasowicz
- Department of Surgery, Elisabeth-Twee Steden hospital, Tilburg, The Netherlands
| | - Gerard Vreugdenhil
- Department of Internal Medicine, Máxima Medical Centre, Eindhoven and Veldhoven, The Netherlands
| | - Floortje Mols
- CoRPS-Center of Research on Psychological Disorders and Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands.
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.
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Ribbing Wilén H, Blom J. Interval cancer after two rounds of a Swedish population-based screening program using gender-specific cut-off levels in fecal immunochemical test. J Med Screen 2024; 31:8-14. [PMID: 37455444 PMCID: PMC10878001 DOI: 10.1177/09691413231185722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/17/2023] [Accepted: 05/31/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVE To evaluate interval cancer (IC) after two screening rounds of the Swedish population-based screening program of Stockholm-Gotland applying gender-specific cut-off levels in the fecal immunochemical test (FIT). METHODS All 60- to 69-year-olds invited to screening 2015-2019 were included. The cut-off level for a positive test was 40 µg/g in women and 80 µg/g in men. Screening-detected colorectal cancers (SD CRCs) and ICs were verified in the Swedish Colorectal Cancer Register, and the follow-up time was two years from invitation. The test sensitivity, the IC rate (ICs per 10,000 screening negatives) and the IC incidence (ICs per 100,000 person-years) relative to the background CRC incidence were assessed by gender and age. The FIT levels were compared in men and women for CRCs diagnosed within one year of the sample. RESULTS In the second screening round, 229,187 were invited, and SD CRCs and ICs were diagnosed in 193 and 144, respectively. The IC rate was 8.9 (7.4-10.3) and test sensitivity 0.61 (0.55-0.66), and was similar in men and women. For two screening rounds, the IC rate was significantly higher in men than in women, but the IC incidence/ background CRC incidence was similar in both genders. The FIT levels in female participants with CRC were significantly lower overall, and in early-staged CRCs as compared to men, and proximal localization was more common in women. In multivariable analysis, FIT levels were significantly lower in proximal CRCs. CONCLUSION Over two rounds, the IC incidence relative to the background CRC incidence was similar in men and women supporting a gender-specific screening strategy. The results could be explained by lower FIT levels in women due to proximal CRC localization.
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Affiliation(s)
- Hanna Ribbing Wilén
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden
| | - Johannes Blom
- Department of Clinical Science and Education Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm, Sweden
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Hansen LØ, Fürst MB, Bjørsum-Meyer T, Schelde-Olesen B, Deding U, Kaalby L. Factors associated with negative colonoscopy in participants with a positive faecal immunochemical test from the Danish Colorectal Cancer Screening Program - a population-based study. Colorectal Dis 2024; 26:476-485. [PMID: 38297072 DOI: 10.1111/codi.16886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/19/2023] [Accepted: 01/06/2024] [Indexed: 02/02/2024]
Abstract
AIM In the Danish Colorectal Cancer Screening Program (DCCSP), 37% of participants undergoing colonoscopy have a negative result with no obvious findings that can be attributed to a positive faecal immunochemical test (FIT). The aim of this work was to identify predictors for a negative colonoscopy in DCCSP participants with a positive FIT. METHOD We included 73 655 FIT-positive DCCSP participants using the Danish Colorectal Cancer Screening Database and linked their screening results with data from several other national health registers. We stratified participants by all predictors, and compared them using multivariate logistic regression analysis. Results are reported as odds ratios (ORs). RESULTS We found that having a condition linked to gastrointestinal bleeding, for example fissures, haemorrhoids and inflammatory bowel disease, was strongly associated with the probability of having a negative colonoscopy [OR 2.77 (95% CI 2.59, 2.96)]. FIT concentration was inversely related to the probability of a negative colonoscopy, the OR decreased steadily from 0.79 (95% CI 0.75, 0.83) in the 40-59 μg/g group, to 0.44 (95% CI 0.42, 0.46) in the ≥200 μg/g group. Women had a 1.64 (95% CI 1.59, 1.70) times higher probability of a negative colonoscopy than men. CONCLUSION Our findings indicate that baseline conditions linked to gastrointestinal bleeding are an associating factor with having a negative colonoscopy. The same is true for low FIT concentration and female sex. Further studies with similar findings could suggest that an incorporation of these factors into a personalized screening approach by differentiating between diagnostic modalities could improve the process for the participant while alleviating the health care system.
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Affiliation(s)
| | | | - Thomas Bjørsum-Meyer
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Benedicte Schelde-Olesen
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ulrik Deding
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Lasse Kaalby
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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van Toledo DEFWM, Breekveldt ECH, IJspeert JEG, van Vuuren AJ, van Kemenade FJ, Ramakers C, Nagtegaal ID, van Leerdam ME, Spaander MCW, Lansdorp-Vogelaar I, Toes-Zoutendijk E, Dekker E. Advanced serrated polyps as a target of screening: detection rate and positive predictive value within a fecal immunochemical test-based colorectal cancer screening population. Endoscopy 2023; 55:526-534. [PMID: 36323332 DOI: 10.1055/a-1971-3488] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
BACKGROUND : Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on advanced adenomas and CRC only. We assessed the ASP detection rate, and positive predictive value (PPV) including ASPs in a fecal immunochemical test (FIT)-based screening program. METHODS : We analyzed the findings of follow-up colonoscopies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data were retrieved from the national screening and pathology database. An ASP was defined as any serrated polyp of ≥ 10 mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with ≥ 1 ASP. PPV was originally defined as the proportion of individuals with a CRC or advanced adenoma. The updated PPV definition included CRCs, advanced adenomas, and/or ASPs. RESULTS : 322 882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9 %. ASPs were detected more often in women than men (6.3 % vs. 5.6 %; P < 0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70 + were 5.2 %, 6.1 %, 6.1 %, and 5.9 %, respectively (P < 0.001). The PPV for CRCs and advanced adenomas was 41.1 % and increased to 43.8 % when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). CONCLUSIONS : 5.9 % of FIT-positive screenees had ASPs, but half of these were detected in combination with a CRC or advanced adenoma. Therefore, including ASPs results in a small increase in the yield of FIT-based screening.
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Affiliation(s)
- David E F W M van Toledo
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands
| | - Emilie C H Breekveldt
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Joep E G IJspeert
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands
| | - Anneke J van Vuuren
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Folkert J van Kemenade
- Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Christian Ramakers
- Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.,Department of Gastroenterology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Amsterdam, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Esther Toes-Zoutendijk
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands
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9
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Núñez Rodríguez MªH, Díez Redondo P, Riu Pons F, Cimavilla M, Loza A, Perez-Miranda M. Findings in the distal and proximal colon in colonoscopy screening after positive FIT and related pre-procedure factors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS : ORGANO OFICIAL DE LA SOCIEDAD ESPANOLA DE PATOLOGIA DIGESTIVA 2022; 114:719-724. [PMID: 35285657 DOI: 10.17235/reed.2022.8409/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Colonoscopy is the gold standard method for the early diagnosis and prevention of colorectal cancer (CRC). Screening programs include immune determination of blood in feces. Regardless of the method used, proximal colon lesions appear to be detected less frequently. OBJECTIVE Analyze the characteristics of proximal and distal lesions and possible predisposing factors. METHODS A cross-sectional study was performed of 692 patients from the CRC screening program with FIT ≥ 100ngHb/ml (October 2017 - October 2018). The right colon was examined twice as patients were participating in a randomized clinical trial to re-evaluate the right colon by forward-viewing endoscope or proximal retroflexion. The adenoma detection rate (ADR), advanced neoplasia (AN) and CRC in the proximal and distal colon, the histological and morphological characteristics in each section were analyzed. RESULTS 52.9% of the patients were male, with a mean age of 59.5 years (SD: 7.6). 1490 polyps were found and the ADR was 57.7% (distal 42% and proximal 37%). Detection rates were 45.8% for AN, 40.9% for advanced adenomas, 5.2% for advanced SSL and CRC was diagnosed in 4.8% of patients. Males had more AN than females. The mean age of patients with AN was significantly higher. AN were associated with smoking and alcohol consumption (p=0.0001). Globally, FIT levels were higher in patients with AN (p=0.003). Sixty-six per cent of cancers were distally located and 61.3% of CRC were diagnosed in the early stages. CONCLUSIONS In an average-risk asymptomatic population undergoing colonoscopy after positive FIT, AN were more common in the distal colon in males, older patients, smokers and those with alcohol intake.
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Affiliation(s)
| | | | | | | | - Andrea Loza
- Endoscopias/Digestivo, Hospital Santos Reyes
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10
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Clark GRC, Steele RJC, Fraser CG. Strategies to minimise the current disadvantages experienced by women in faecal immunochemical test-based colorectal cancer screening. Clin Chem Lab Med 2022; 60:1496-1505. [PMID: 35848100 DOI: 10.1515/cclm-2022-0583] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 07/04/2022] [Indexed: 08/16/2024]
Abstract
Currently, women are disadvantaged compared to men in colorectal cancer (CRC) screening, particularly in programmes that use faecal immunochemical tests for haemoglobin (FIT) followed by colonoscopy. Although there is no single cause for all the known disadvantages, many can be attributed to the ubiquitous finding that women have lower faecal haemoglobin concentrations (f-Hb) than men; there are many plausible reasons for this. Generally, a single f-Hb threshold is used in CRC screening programmes, leading to lower positivity for women than men, which causes poorer outcomes for women, including lower CRC detection rate, higher interval cancer (IC) proportion, and higher CRC mortality. Many of the now widely advocated risk scoring strategies do include factors taking account of sex, but these have not been extensively piloted or introduced. Using different f-Hb thresholds for the sexes seems advantageous, but there are difficulties, including deciding which characteristic should be selected to achieve equivalency, for example, positivity, IC proportions, or specificity. Moreover, additional colonoscopy resources, often constrained, would be required. Governments and their agencies should be encouraged to prioritise the allocation of resources to put simple strategies into practice, such as different f-Hb thresholds to create equal positivity in both sexes.
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Affiliation(s)
- Gavin R C Clark
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland, UK
| | - Robert J C Steele
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland, UK
| | - Callum G Fraser
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland, UK
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11
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One or two faecal immunochemical tests in an organised population-based colorectal cancer screening programme in Murcia (Spain). J Med Screen 2022; 29:231-240. [PMID: 35578555 DOI: 10.1177/09691413221094919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate. METHODS Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when >20 µg Hb/g faeces; two FIT, positive when either was >20 µg Hb/g faeces; and two FIT, positive when the mean was >20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected. RESULTS In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was >20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is >20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT. CONCLUSIONS In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed.
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12
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Thomas C, Mandrik O, Whyte S, Saunders CL, Griffin SJ, Usher‐Smith JA. Should colorectal cancer screening start at different ages for men and women? Cost-effectiveness analysis for a resource-constrained service. Cancer Rep (Hoboken) 2021; 4:e1344. [PMID: 33533190 PMCID: PMC8388164 DOI: 10.1002/cnr2.1344] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/18/2020] [Accepted: 01/13/2021] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Men have a greater risk of colorectal cancer (CRC) than women, but population screening currently starts at the same age for both sexes. AIM This analysis investigates whether, in a resource-constrained setting, it would be more effective and cost-effective for men and women to start screening for CRC at different ages. METHODS AND RESULTS An economic modeling analysis was carried out using the Microsimulation Model in Cancer of the Bowel to compare sex-stratification against screening everyone from the same age, taking an English National Health Service perspective. Screening men from age 56 and women from age 60, rather than screening everyone from age 58 using a Fecal Immunochemical Test (FIT) threshold of 120 μg/g is expected to produce an additional 0.0004 QALYs for a cost of £0.55 per person at model start (Incremental Cost-effectiveness Ratio = £1392), and to reduce CRC cases and mortality by 25 and 19 per 100 000 people respectively, while using a similar amount of screening resources. Probabilistic sensitivity analysis indicates a 61% probability that sex-stratification is more cost-effective than screening everyone at age 58. Similar benefits of sex-stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50. CONCLUSION Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost-effective and gain more health benefits overall than strategies where men and women start screening at the same age.
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Affiliation(s)
- Chloe Thomas
- School of Health and Related ResearchUniversity of SheffieldSheffieldUK
| | - Olena Mandrik
- School of Health and Related ResearchUniversity of SheffieldSheffieldUK
| | - Sophie Whyte
- School of Health and Related ResearchUniversity of SheffieldSheffieldUK
| | - Catherine L. Saunders
- The Primary Care Unit, Department of Public Health and Primary CareUniversity of Cambridge, School of Clinical MedicineCambridgeUK
| | - Simon J. Griffin
- The Primary Care Unit, Department of Public Health and Primary CareUniversity of Cambridge, School of Clinical MedicineCambridgeUK
| | - Juliet A. Usher‐Smith
- The Primary Care Unit, Department of Public Health and Primary CareUniversity of Cambridge, School of Clinical MedicineCambridgeUK
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13
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Vanaclocha-Espi M, Ibáñez J, Molina-Barceló A, Valverde-Roig MJ, Nolasco A, Pérez-Riquelme F, de la Vega M, Portillo I, Salas D. Optimal cut-off value for detecting colorectal cancer with fecal immunochemical tests according to age and sex. PLoS One 2021; 16:e0254021. [PMID: 34270590 PMCID: PMC8284629 DOI: 10.1371/journal.pone.0254021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/17/2021] [Indexed: 01/22/2023] Open
Abstract
In the fecal immunological test, a suitable cut-off value may be selected to classify results as either positive or negative. Our aim is to estimate the optimal cut-off value for detecting colorectal cancer in different age and sex groups. This is a multicentric retrospective cohort study of participants in CRC screening programs with FIT between 2006 and 2012. A total of 545,505 participations were analyzed. Cancers diagnosed outside of the program were identified after a negative test result (IC_test) up until 2014. The Wilcoxon test was used to compare fecal hemoglobin levels. ROC curves were used to identify the optimal cut-off value for each age and sex group. Screening program results were estimated for different cut-off values. The results show that the Hb concentration was higher in colorectal cancer (average = 179.6μg/g) vs. false positives (average = 55.2μg/g), in IC_test (average = 3.1μg/g) vs. true negatives (average = 0μg/g), and in men (average = 166.2μg/g) vs. women (average = 140.2μg/g) with colorectal cancer. The optimal cut-off values for women were 18.3μg/g (50-59y) and 14.6μg/g (60-69y), and 16.8μg/g (50-59y) and 19.9μg/g (60-69y) for men. Using different cut-off values for each age and sex group lead to a decrease in the IC_test rate compared to the 20μg/g cut-off value (from 0.40‰ to 0.37‰) and an increase in the false positive rate (from 6.45% to 6.99%). Moreover, test sensitivity improved (90.7%), especially in men and women aged 50-59y (89.4%; 90%) and women aged 60-69y (90.2%). In conclusion, the optimal cut-off value varies for different sex and age groups and the use of an optimal cut-off value for each group improves sensitivity and leads to a small decrease in IC_tests, but also to a larger increase in false positives.
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Affiliation(s)
- Mercedes Vanaclocha-Espi
- Foundation for the Promotion of Health and Biomedical Research-Public Health Research FISABIO–Public Health Research, Valencia, Spain
| | - Josefa Ibáñez
- Foundation for the Promotion of Health and Biomedical Research-Public Health Research FISABIO–Public Health Research, Valencia, Spain
- General Directorate Public Health, Valencian Community, Spain
| | - Ana Molina-Barceló
- Foundation for the Promotion of Health and Biomedical Research-Public Health Research FISABIO–Public Health Research, Valencia, Spain
| | | | | | - Francisco Pérez-Riquelme
- General Directorate of Public Health, Murcia Region, Spain
- Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), University Hospital “Virgen de la Arrixaca”, University of Murcia, Murcia, Spain
| | | | | | - Dolores Salas
- Foundation for the Promotion of Health and Biomedical Research-Public Health Research FISABIO–Public Health Research, Valencia, Spain
- General Directorate Public Health, Valencian Community, Spain
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14
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Clark GRC, Strachan JA, McPherson A, Digby J, Mowat C, Steele RJC, Fraser CG. Faecal haemoglobin distributions by sex, age, deprivation and geographical region: consequences for colorectal cancer screening strategies. Clin Chem Lab Med 2021; 58:2073-2080. [PMID: 32324157 DOI: 10.1515/cclm-2020-0268] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/02/2020] [Indexed: 02/07/2023]
Abstract
Objectives Faecal immunochemical tests for haemoglobin (FIT) are becoming widely used in colorectal cancer (CRC) screening and assessment of symptomatic patients. Faecal haemoglobin concentration (f-Hb) thresholds are used to guide subsequent investigation. We established the distributions of f-Hb in a large screening population by sex, age, deprivation and geography. Methods Single estimates of f-Hb were documented for all individuals participating in the first 18 months of the Scottish Bowel Screening Programme (SBoSP). The distributions of f-Hb were generated for all participants, all men and women, and men and women by age quintile and deprivation quintile. Distributions were also generated by geographical region for all participants, men and women, and by deprivation. Comparisons of f-Hb distributions with those found in a pilot evaluation of FIT and three other countries were performed. Results f-Hb was documented for 887,248 screening participants, 422,385 men and 464,863 women. f-Hb varied by sex, age, deprivation quintile and geographical region. The f-Hb distributions by sex and age differed between the SBoSP and the pilot evaluation and the three other countries. Conclusions f-Hb is higher in men than in women and increases with age and deprivation in both sexes. f-Hb also varies by geographical region, independently of deprivation, and by country. The f-Hb distribution estimated by pilot evaluation may not represent the population distribution. Decision limits have advantages over reference intervals. Use of partitioned f-Hb thresholds for further investigation, based on the data generated, has advantages and disadvantages, as do risk scores based on a spectrum of influencing variables.
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Affiliation(s)
- Gavin R C Clark
- Information Services Division, NHS National Services Scotland, Edinburgh, Scotland, UK.,Centre for Research into Cancer Prevention and Screening, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Judith A Strachan
- Department of Blood Sciences and Scottish Bowel Screening Laboratory, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Alisson McPherson
- Scottish Bowel Screening Laboratory, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Jayne Digby
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Craig Mowat
- Department of Gastroenterology, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Robert J C Steele
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Callum G Fraser
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
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15
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Ribbing Wilén H, Saraste D, Blom J. Gender-specific cut-off levels in colorectal cancer screening with fecal immunochemical test: A population-based study of colonoscopy findings and costs. J Med Screen 2021; 28:439-447. [PMID: 34106777 DOI: 10.1177/09691413211020035] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE In the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm-Gotland using the fecal immunochemical test (FIT), gender-specific cut-off levels of fecal hemoglobin are applied, since previous studies have indicated a lower sensitivity of FIT for CRC in women. The aim was to evaluate the diagnostic yield and the screening costs overall and per detected CRC of this strategy. METHODS All individuals aged 60-69 invited to screening in 2015-2017 were included. Cut-off level for positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. The yield of CRC and screening cost for the study period were assessed and compared to cut-off levels of 80 µg/g in both genders. RESULTS Approximately 230,000 individuals were invited. Overall participation rates were 72% in women and 65% in men (p < 0.05). FIT was positive in 4256 individuals (2.7% in both genders). In 3758 colonoscopies, 258 (6.9%) CRCs were detected. The positive predictive value for CRC was significantly higher in men (8.3% vs. 5.8%). In 120 women with CRC, 28 (23%) had FIT < 80 µg/g. Negative colonoscopies were more common in women (24% vs. 17%, p < 0.05). Total costs for the study period were 52,000,000SEK (≈5,200,000€), i.e. 16% higher compared to using cut-off levels of 80 µg/g in both genders, and corresponding to a 3% increment in cost per detected CRC. CONCLUSION The high rate of CRC detected in women in the lowest FIT category outweighs the minor reduction in screening costs if the same cut-off level was used as for men.
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Affiliation(s)
- Hanna Ribbing Wilén
- Department of Clinical Science and Education, Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm.,Trauma & Reparative Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Deborah Saraste
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Södersjukhuset, Stockholm, Sweden
| | - Johannes Blom
- Department of Clinical Science and Education, Södersjukhuset (KI SÖS), Karolinska Institutet, Stockholm
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16
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Keys MT, Serra-Burriel M, Martínez-Lizaga N, Pellisé M, Balaguer F, Sánchez A, Bernal-Delgado E, Castells A. Population-based organized screening by faecal immunochemical testing and colorectal cancer mortality: a natural experiment. Int J Epidemiol 2021; 50:143-155. [PMID: 33211822 DOI: 10.1093/ije/dyaa166] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Population-based organized screening programmes for colorectal cancer (CRC) are underway worldwide, with many based on the faecal immunochemical test (FIT). No clinical trials assessing FIT compared with no screening are planned, and few studies have assessed the population impact of such programmes. METHODS Before 2010, 11 out of 50 Spanish provinces initiated population-based organized screening programmes with FIT for an average-risk population aged 50-69 years. We used a quasi-experimental design across Spanish provinces between 1999 and 2016 to evaluate their impact on population age-standardized mortality and incidence rates due to CRC. Difference-in-differences and synthetic control analyses were performed to test for validation of statistical assumptions and to assess the dynamics of screening-associated changes in outcomes over time. RESULTS No differences in outcome trends between exposed (n = 11) and control (n = 36) provinces were observed for up to 7 years preceding the implementation of screening. Relative to controls, exposed provinces experienced a mean increase in age-standardized incidence of 10.08% [95% confidence interval (CI) (5.09, 15.07)] 2 years after implementation, followed by a reduction in age-standardized mortality rates due to CRC of 8.82% [95% CI (3.77, 13.86)] after 7 years. Results were similar for both women and men. No associated changes were observed in adjacent age bands not targeted by screening, nor for 10 other major causes of death in the exposed provinces. CONCLUSIONS FIT-based organized screening in Spain was associated with reductions in population colorectal cancer mortality. Further research is warranted in order to assess the replicability and external validity of our findings, and on gender-specific use of FIT in organized screening.
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Affiliation(s)
- Matthew T Keys
- Department of Public Health, Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark.,Department of Economics, Center for Research in Health and Economics (CRES), Pompeu Fabra University, Barcelona, Spain
| | - Miquel Serra-Burriel
- Department of Economics, Center for Research in Health and Economics (CRES), Pompeu Fabra University, Barcelona, Spain
| | - Natalia Martínez-Lizaga
- Data Science in Health Services and Policy Research, Institute for Health Sciences in Aragón (IACS), Zaragoza, Spain.,Spanish Health Services Research Network on Chronic Diseases (REDISSEC), Zaragoza, Spain
| | - Maria Pellisé
- Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Barcelona, Spain
| | - Francesc Balaguer
- Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Barcelona, Spain
| | - Ariadna Sánchez
- Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Barcelona, Spain
| | - Enrique Bernal-Delgado
- Data Science in Health Services and Policy Research, Institute for Health Sciences in Aragón (IACS), Zaragoza, Spain.,Spanish Health Services Research Network on Chronic Diseases (REDISSEC), Zaragoza, Spain
| | - Antoni Castells
- Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Barcelona, Spain
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17
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Tiankanon K, Aniwan S, Rerknimitr R. Current Status of Colorectal Cancer and Its Public Health Burden in Thailand. Clin Endosc 2021; 54:499-504. [PMID: 33721484 PMCID: PMC8357574 DOI: 10.5946/ce.2020.245-iden] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 11/13/2020] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC) accounts for approximately 10.3% of new cancer cases in Thailand and is currently the 3rd most prevalent cancer found among the Thai population. Starting in 2017, the Thai government announced the national CRC screening program as a response to this important issue. Among the 70 million people currently residing in Thailand, 14 million require screening, while there are approximately a total of 1,000 endoscopists available to perform colonoscopy. Due to the limited resources and shortage of endoscopists in Thailand, applying a population-based one-step colonoscopy program as a primary screening method is not feasible. To reduce colonoscopy workload, with the help of others, including village health volunteers, institution-based health personnel, reimbursement coders, pathologists, and patients due for CRC screening, a two-step approach of one-time fecal immunochemical test (FIT), which prioritizes and filters out subjects for colonoscopy, is chosen. Moreover, additional adjustments to the optimal FIT cutoff value and the modified Asia-Pacific Colorectal Screening risk score, including body weight, were proposed to stratify the priority of colonoscopy schedule. This article aims to give an overview of the past and current policy developmental strategies and the current status of the Thailand CRC screening program.
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Affiliation(s)
- Kasenee Tiankanon
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand.,Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
| | - Satimai Aniwan
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand.,Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Chulalongkorn University, Bangkok, Thailand.,Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
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18
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Peng L, Balavarca Y, Niedermaier T, Weigl K, Hoffmeister M, Brenner H. Risk-Adapted Cutoffs in Colorectal Cancer Screening by Fecal Immunochemical Tests. Am J Gastroenterol 2020; 115:1110-1116. [PMID: 32618662 DOI: 10.14309/ajg.0000000000000579] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Fecal immunochemical tests (FITs) for hemoglobin are increasingly used in colorectal cancer (CRC) screening. The use of uniform positivity thresholds (cutoffs) within screening populations is expected to imply lower positive predictive values (PPVs) and higher numbers of colonoscopies needed (numbers needed to scope [NNSs]) to detect advanced neoplasms among screening participants at lower risk compared with those at higher risk. We aimed to assess such variation and its potential implications in a large screening cohort. METHODS A quantitative FIT (FOB Gold; Sentinel Diagnostics, Milan, Italy) was conducted in fecal samples collected by 4,332 participants of screening colonoscopy before bowel preparation. Participants were classified into 3 risk groups (low, medium, and high) by tertiles of a previously derived risk-factor-based risk score. We determined the variation of PPVs and NNSs for detecting advanced neoplasms (i.e., CRC or advanced adenoma) when using the same FIT cutoffs and variation of FIT cutoffs that would yield uniform PPVs across risk groups. RESULTS When a fixed FIT cutoff of 10 μg/g was used, the PPV increased from 23.3% to 41.8% from the low- to the high-risk group, with NNS decreasing from 4.3 to 2.4 (P < 0.001). Similar variations of PPVs and NNSs across risk groups were observed at higher FIT cutoffs. When risk group-specific cutoffs were defined to achieve fixed PPVs of 25%, 30%, and 35% across all risk groups, cutoffs varied from 5.3 to 11.4, 6.5 to 18.7, and 7.5 to 31.0 μg hemoglobin/g feces, respectively, between high- and low-risk groups (P < 0.05 for all differences). DISCUSSION Using risk-adapted cutoffs may help to achieve target levels of PPV and NNS and might be an option to consider for personalized FIT-based CRC screening.
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Affiliation(s)
- Le Peng
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Yesilda Balavarca
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tobias Niedermaier
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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19
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Ribbing Wilén H, Blom J, Höijer J, Andersson G, Löwbeer C, Hultcrantz R. Fecal immunochemical test in cancer screening - colonoscopy outcome in FIT positives and negatives. Scand J Gastroenterol 2019; 54:303-310. [PMID: 30907196 DOI: 10.1080/00365521.2019.1585569] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: Fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, but evaluations of multiple sample strategies in colonoscopy screening cohorts are rare. The aim of this study was to assess accuracy of FIT for advanced neoplasia (AN) with two fecal samples in a colonoscopy screening cohort. Materials and methods: The study comprised 1155 participants of the colonoscopy arm in SCREESCO (Screening of Swedish Colons, NCT02078804), a randomized controlled study on CRC screening of 60-year-olds from the Swedish average-risk population. Participants provided two FIT samples prior to colonoscopy. First sample, mean of two, and any of the two samples above cut off level were assessed. Colonoscopy findings (CRC, advanced adenoma (AA), AN (CRC + AA) and adenoma characteristics) were evaluated in uni- and multivariable analysis in relation to FIT positivity (at ≥10 µg hemoglobin (Hb)/g). Results: Of 1155 invited, 806 (416 women, 390 men) participated. CRC, AA and non-AA were found in one (0.1%), 80 (9.9%) and 145 (18%), respectively. Sensitivity and specificity for AN were 20%/93%, 25%/92% and 26%/89% for first, mean of two and any of the two samples respectively at cut off level 10 µg/g, corresponding to 60 (74%)-65 (80%) participants with missed AN. The difference in sensitivity between screening strategies was non-significant. The specificity for first sample was significantly higher than for any of the two samples at cut off 10 µg/g (p = .02) and 20 µg/g (p = .04). FIT positivity in participants with adenoma was associated with pedunculated shape (p = .007) and high-risk dysplasia (p = .009). Conclusions: In an average-risk colonoscopy screening cohort of 60-year-olds, sensitivity for AN was modest and did not increase when using two samples instead of one. FIT predominantly detected adenomas with pedunculated shape and high-risk dysplasia, and participants with flat or broad based adenomas may thus be missed in screening.
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Affiliation(s)
- Hanna Ribbing Wilén
- a Department of Clinical Science, Intervention and Technology , Karolinska Institutet , Stockholm , Sweden.,b Trauma and Reparative Medicine, Division of Emergency Surgery , Karolinska University Hospital Huddinge , Stockholm , Sweden
| | - Johannes Blom
- c Department of Molecular Medicine and Surgery , Karolinska Institutet and Stockholm County Council , Stockholm , Sweden
| | - Jonas Höijer
- d Unit of Biostatistics Institute of Environmental Medicine , Karolinska Institutet , Stockholm , Sweden
| | - Gaya Andersson
- e Department of Clinical Chemistry , Aleris Medilab , Täby , Sweden
| | - Christian Löwbeer
- e Department of Clinical Chemistry , Aleris Medilab , Täby , Sweden.,f Department of Laboratory Medicine, Division of Clinical Chemistry , Karolinska Institutet , Stockholm , Sweden
| | - Rolf Hultcrantz
- g Department of Medicine , Solna Karolinska Institutet , Stockholm , Sweden
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Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance? Cancers (Basel) 2019; 11:cancers11010120. [PMID: 30669538 PMCID: PMC6356298 DOI: 10.3390/cancers11010120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/15/2019] [Accepted: 01/17/2019] [Indexed: 02/06/2023] Open
Abstract
A variety of fecal immunochemical tests (FITs) are used for colorectal cancer screening. FIT performance could be improved further. It is unclear, whether the combination of different FITs with different analytical characteristics (such as, different antibodies for the detection of fecal hemoglobin) can yield a better diagnostic performance. Fecal samples were obtained from 2042 participants of screening colonoscopy. All participants with advanced neoplasm (AN, colorectal cancer (n = 16) or advanced adenoma (n = 200)) and 300 randomly selected participants without AN were included. Nine quantitative FITs were evaluated simultaneously. Sensitivity and specificity was calculated for single tests (n = 9) and for their pairwise test combinations (n = 36) (requiring either both FITs (P++) or at least one FIT (P+) to be positive for defining a positive test result). Mean age of the participants (n = 516) was 63 (range: 50–79) years and 56% were men. At cutoffs yielding a specificity of 96.7% for single FITs, the median gain in specificity by P++ combination was +1.0%, whereas the median loss in sensitivity for AN was −4.2%. For P+ combination the median gain in sensitivity for AN was +2.8%, at a prize of median loss of −1.0% of specificity. Combinations of different FITs do not yield any relevant gain in diagnostic performance.
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Ribbing Wilén H, Blom J, Höijer J, Hultcrantz R. Fecal immunochemical test in colorectal cancer screening: Colonoscopy findings by different cut-off levels. J Gastroenterol Hepatol 2019; 34:103-112. [PMID: 29968937 DOI: 10.1111/jgh.14373] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/20/2018] [Accepted: 06/23/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, but number of tests and cut-off level differ by program. The aim was to evaluate CRC screening with two FIT samples in average-risk 60-year-old men and women and to investigate hemoglobin (Hb) level in correlation to adenoma characteristics. METHODS We analyzed a cohort from Screening of Swedish Colons trial where participants with at least one of two FIT samples ≥10 μg Hb/g are offered colonoscopy. FIT levels and colonoscopy findings were assessed in multivariable analyses. Cut-off levels 10-80 μg Hb/g for one and two samples were assessed. FIT levels and advanced neoplasia (AN) were investigated by gender. RESULTS A total of 12 383 participated and 1182 positives (551 women) completed colonoscopy diagnosing 27 (2.3%) CRC and 269 (23%) advanced adenomas (AA). Median FIT level was 241.0 and 23.8 for CRC and AA compared with 13.4-15.8 in other subgroups (P = 0.002) correlating with adenoma size (P = 0.038). CRC was detected in 22 and 19 subjects for the first sample at cut-off 20 and 40 μg Hb/g, compared with 20 and 17 for the mean of two samples at cut-off 40 and 80 μg Hb/g (P < 0.05). Men had more AN (CRC + AA), (P = 0.003). In women, similar number of AN would be detected with cut-off lowered from 40 to 20 or from 80 to 40 μg Hb/g, requiring additional 26-34% colonoscopies. CONCLUSION In average-risk 60-year-olds, FIT was higher in participants with AN and correlated with adenoma size. FIT screening with one sample at low cut-off detected more CRC than two samples at higher cut-off. Applying lower cut-off in women to equalize gender differences in AN would result in considerable increase in colonoscopy workload.
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Affiliation(s)
- Hanna Ribbing Wilén
- Department of Clinical Science, Intervention and Technology, Karolinska Institute, and Trauma and Reparative Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Johannes Blom
- Department of Molecular Medicine and Surgery, Karolinska Institute and Stockholm County Council, Stockholm, Sweden
| | - Jonas Höijer
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Rolf Hultcrantz
- Department of Medicine, Karolinska Institute, Stockholm, Sweden
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Participant-Related Risk Factors for False-Positive and False-Negative Fecal Immunochemical Tests in Colorectal Cancer Screening: Systematic Review and Meta-Analysis. Am J Gastroenterol 2018; 113:1778-1787. [PMID: 30158713 PMCID: PMC6768609 DOI: 10.1038/s41395-018-0212-7] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 06/29/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Colorectal cancer (CRC) screening using fecal immunochemical tests (FIT) may reduce CRC-related mortality but its effectiveness is influenced by the limited accuracy of FIT. Identifying individuals at increased risk of a false FIT result could improve screening, but the available evidence is conflicting. We performed a systematic review and meta-analysis on risk factors for false-positive and false-negative FIT results in CRC screening. METHODS A systematic search in MEDLINE, EMBASE, and Cochrane Library identified publications (before 29 January 2017) on risk factors (known at time of FIT invitation) associated with false FIT results (presence/absence of advanced neoplasia) in a CRC screening setting. Risk of bias was assessed using QUIPS. In meta-analysis, summary relative risk ratios and corresponding 95% confidence intervals were calculated for each risk factor. RESULTS Of 518 records identified, 14 studies with 54,499 participants in total were included for analysis. In meta-analysis, male sex was associated with a significantly lower risk of false-positivity (RR 0.84, CI 0.74-0.94), whereas participants using non-steroidal anti-inflammatory drugs (NSAIDs) had a higher risk (RR 1.16, CI 1.06-1.27). The use of anticoagulants was most frequently studied, without a significant effect on FIT positivity. Males (RR 1.83, CI 1.53-2.19), participants with a family history for CRC (RR 1.61, CI 1.19-2.15), hyperglycemia (RR 1.29, CI 1.02-1.65), hypertension (RR 1.50, CI 1.14-1.98), obesity (RR 1.38, CI 1.11-1.71), and (former) smokers (RR 1.93, CI 1.52-2.45) were all at significantly higher risk for false-negative results. Age was not found to have a systematic effect on either FIT false-positivity or false-negativity in meta-analysis. CONCLUSIONS Multiple risk factors, known at time of FIT invitation, are associated with false FIT results in CRC screening. This information can be used to identify populations risking false reassurance after a negative result or unnecessary colonoscopy after a positive result, and to further optimize CRC screening effectiveness.
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Alsayid M, Singh MH, Issaka R, Laleau V, Day L, Lee J, Allison J, Somsouk M. Yield of Colonoscopy After a Positive Result From a Fecal Immunochemical Test OC-Light. Clin Gastroenterol Hepatol 2018; 16:1593-1597.e1. [PMID: 29660528 PMCID: PMC6151285 DOI: 10.1016/j.cgh.2018.04.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 03/14/2018] [Accepted: 04/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about its ability to detect CRC in large average-risk populations. METHODS We performed a retrospective cohort study of patients (50-75 years old) in the San Francisco Health Network who were screened for CRC by OC-Light FIT from August 2010 through June 2015. Patients with a positive result were referred for colonoscopy. We used electronic health records to identify participants with positive FIT results, and collected results from subsequent colonoscopies and pathology analyses. The FIT positive rate was calculated by dividing the number of positive FIT results by the total number of FIT tests completed. The primary outcome was the positive rate from OC-Light FIT and yield of neoplasms at colonoscopy. Secondary outcomes were findings from first vs subsequent rounds of testing, and how these varied by sex and race. RESULTS We collected result from 35,318 FITs, performed on 20,886 patients; 2930 patients (8.3%) had a positive result, and 1558 patients completed the follow-up colonoscopy. A positive result from the FIT identified patients with CRC with a positive predictive value of 3.0%, and patients with advanced adenoma with a positive predictive value of 20.8%. The FIT positive rate was higher during the first round of testing (9.4%) compared to subsequent rounds (7.4%) (P < .01). The yield of CRC in patients with a positive result from the first round of the FIT was 3.7%, and decreased to 1.8% for subsequent rounds (P = .02). CONCLUSIONS In a retrospective analysis of patients in a diverse safety-net population who underwent OC-Light FIT for CRC screening, we found that approximately 3% of patients with a positive result from a FIT to have CRC and approximately 21% to have advanced adenoma.
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Affiliation(s)
- Muhammad Alsayid
- Department of Health Services, University of Washington School of Public Health, Seattle, Washington
| | | | - Rachel Issaka
- Clinical Research & Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington
| | - Victoria Laleau
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Lukejohn Day
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Jeffrey Lee
- Kaiser Permanente Division of Research, Vallejo, California; Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California
| | - James Allison
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California; Kaiser Permanente Division of Research, Vallejo, California
| | - Ma Somsouk
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California; Center for Vulnerable Populations, University of California, San Francisco, San Francisco, California.
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Brenner H, Qian J, Werner S. Variation of diagnostic performance of fecal immunochemical testing for hemoglobin by sex and age: results from a large screening cohort. Clin Epidemiol 2018; 10:381-389. [PMID: 29670403 PMCID: PMC5896664 DOI: 10.2147/clep.s155548] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective Fecal immunochemical tests (FITs) for hemoglobin in stool are increasingly used for colorectal cancer screening. Reported sensitivities and specificities have strongly varied between studies, but it is unclear to what extent such variation reflects differences between tests or between study population characteristics. We aimed to evaluate the key parameters of FIT performance for detecting advanced neoplasia (AN) according to sex and age. Methods Sex- and age-specific sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) for detecting AN of a quantitative FIT (FOB Gold®) were evaluated among 3211 men and women aged 50–79 years who underwent screening colonoscopy in Germany. Results At the cutoff recommended by the manufacturer (17 µg hemoglobin/g feces), sensitivity was higher (51.2% versus 34.7%, p=0.004) and specificity was lower (91.0% versus 94.8%, p<0.001) among 65–79 year-old participants compared with 50–64 year-old participants. PPVs and NPVs did not differ significantly between age groups. However, higher NPVs were observed among women compared with men (94.7% versus 92.5%, p=0.015). Specificity was also higher among women compared with men (94.7% versus 92.3%, p=0.007), while there was only a little variation in sensitivity (40.3% versus 41.8%, p=0.789) according to sex. In joint stratification by both factors, sensitivity ranged from 34.1% (95% CI 24.2%–45.2%) in 50–64 year-old women to 51.4% (95% CI 39.3%–63.3%) in 65–79 year-old men (p=0.029). The observed age and sex differences were highly consistent across a wide range of alternative cutoffs from 10 to 50 µg hemoglobin/g feces. Conclusion There are major differences in diagnostic performance parameters according to sex and age, which should receive careful attention in the interpretation and comparison of results of FIT-based colorectal cancer screening studies.
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Affiliation(s)
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jing Qian
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Simone Werner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Chen SLS, Hsu CY, Yen AMF, Young GP, Chiu SYH, Fann JCY, Lee YC, Chiu HM, Chiou ST, Chen HH. Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age/Sex-Specific Thresholds for Test Positivity. Cancer Epidemiol Biomarkers Prev 2018; 27:704-709. [PMID: 29593012 DOI: 10.1158/1055-9965.epi-17-0387] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 08/09/2017] [Accepted: 03/23/2018] [Indexed: 11/16/2022] Open
Abstract
Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown.Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a "universal" threshold, receiver-operating-characteristic curve-derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments.Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this "colonoscopy-capacity-adjusted" threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold.Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand.Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity. Cancer Epidemiol Biomarkers Prev; 27(6); 704-9. ©2018 AACR.
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Affiliation(s)
- Sam Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chen-Yang Hsu
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Amy Ming-Fang Yen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Graeme P Young
- Flinders Centre for Innovation in Cancer, Flinders University, Australia
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan.,Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jean Ching-Yuan Fann
- Department of Health Industry Management, School of Healthcare Management, Kainan University, Tao-Yuan, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shu-Ti Chiou
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Cheng Hsin General Hospital, Taipei, Taiwan
| | - Hsiu-Hsi Chen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
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Colorectal Cancer Biomarkers - A New Trend in Early Diagnosis. CURRENT HEALTH SCIENCES JOURNAL 2018; 44:140-146. [PMID: 30746161 PMCID: PMC6320460 DOI: 10.12865/chsj.44.02.08] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/27/2018] [Indexed: 12/12/2022]
Abstract
Colorectal cancer (CRC) is one of the most widespread malignancy, posing as a great challenge due to its high incidence and mortality in both genders. Yet, it also stands as one of the most preventable diseases because of its known malignant transformation mostly from tubular adenomas or serrated polyps, therefore offering a strong incentive to the screening programs that are being developed for this disease. Current diagnosis of CRC has surely evolved along with the evolutionary step in gastrointestinal technology of flexible endoscopy. These innovations have promoted colonoscopy as a primary choice for screening programs of colonic lesions, proving to be of great benefit for patient’s well-being. In this review, we present the current status of CRC screening methods from the non-invasive options to the long developed colonoscopic and imaging techniques. We search through PubMed and Medline databases and chose relevant articles on CRC with focus on blood based biomarkers and stool based tests. Additional relevant publications were also according to the reference lists of firstly identified articles.
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Arana-Arri E, Idigoras I, Uranga B, Pérez R, Irurzun A, Gutiérrez-Ibarluzea I, Fraser CG, Portillo I. Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex? BMC Cancer 2017; 17:577. [PMID: 28851318 PMCID: PMC5576224 DOI: 10.1186/s12885-017-3555-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 08/14/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. METHODS Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. RESULTS We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). CONCLUSIONS This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off.
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Affiliation(s)
- Eunate Arana-Arri
- BioCruces Health Research Institute, Plaza Cruces 12, 48903 Barakaldo, Bizkaia Spain
| | - Isabel Idigoras
- Colorectal Cancer Screening Programme Coordination Center, Bilbao, Spain
| | - Begoña Uranga
- Clinical Biochemistry Service, Donostia University Hospital, Basque Health Service, Donostia, Gipuzkoa Spain
| | - Raquel Pérez
- Clinical Biochemistry Service, Cruces University Hospital, Basque Health Service, Barakaldo, Bizkaia Spain
| | - Ana Irurzun
- Clinical Biochemistry Service, Donostia University Hospital, Basque Health Service, Donostia, Gipuzkoa Spain
| | | | - Callum G. Fraser
- Centre for Research into Cancer Prevention & Screening, University of Dundee, Dundee, Scotland
| | - Isabel Portillo
- Centre for Research into Cancer Prevention & Screening, University of Dundee, Dundee, Scotland
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Aniwan S, Ratanachu-Ek T, Pongprasobchai S, Limsrivilai J, Praisontarangkul OA, Pisespongsa P, Mairiang P, Sangchan A, Sottisuporn J, Wisedopas N, Kullavanijaya P, Rerknimitr R. Impact of Fecal Hb Levels on Advanced Neoplasia Detection and the Diagnostic Miss Rate For Colorectal Cancer Screening in High-Risk vs. Average-Risk Subjects: a Multi-Center Study. Clin Transl Gastroenterol 2017; 8:e113. [PMID: 28796231 PMCID: PMC5587841 DOI: 10.1038/ctg.2017.40] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 07/08/2017] [Indexed: 02/06/2023] Open
Abstract
Objectives: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to identify high-risk subjects for advanced neoplasia. However, the appropriate fecal immunochemical test (FIT) cutoff for high-risk population may be different from that of average-risk population. We aimed to evaluate the FIT performance at different cutoffs in high-risk subjects undergoing colorectal cancer (CRC) screening. Methods: We prospectively enrolled asymptomatic subjects aged 50–75 years. Using the APCS score, subjects were stratified into either the average-risk or high-risk groups. All subjects were tested with one-time quantitative FIT and underwent colonoscopy. We compared the FIT performance for advanced neoplasia between two groups using different cutoffs (5 (FIT5), 10 (FIT10), 20 (FIT20), 30 (FIT30), and 40 (FIT40) μg Hb/g feces). Results: Overall, 1,713 subjects were recruited, and 1,222 (71.3%) and 491 (28.7%) were classified as average-risk and high-risk, respectively. Advanced neoplasia was detected in 90 (7.4%) of the average-risk subjects and 65 (13.2%) of the high-risk subjects. In the high-risk group, by decreasing the cutoff from FIT40 to FIT5, the sensitivity increased by 33.8 percentage points with decreased specificity by 11 percentage points. In the average-risk group, the sensitivity increased by 20 percentage points with decreased specificity by 9.6 percentage points. At the lowest cutoff (FIT5), the number of needed colonoscopies to find one advanced neoplasia was 2.8 and 6.1 for the high-risk and average-risk groups, respectively. Conclusions: Using an appropriate FIT cutoff for CRC screening in high-risk subjects could improve CRC screening performance and reduce the unnecessary colonoscopies. To maintain high sensitivity and specificity for advanced neoplasia, the optimal cutoff FIT in the high-risk subjects should be lower than that in the average-risk subjects.
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Affiliation(s)
- Satimai Aniwan
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | | | - Supot Pongprasobchai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ong-Ard Praisontarangkul
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pises Pisespongsa
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pisaln Mairiang
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Apichat Sangchan
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Jaksin Sottisuporn
- NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand
| | - Naruemon Wisedopas
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pinit Kullavanijaya
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
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Meulen MPVD, Kapidzic A, Leerdam MEV, van der Steen A, Kuipers EJ, Spaander MCW, de Koning HJ, Hol L, Lansdorp-Vogelaar I. Do Men and Women Need to Be Screened Differently with Fecal Immunochemical Testing? A Cost-Effectiveness Analysis. Cancer Epidemiol Biomarkers Prev 2017; 26:1328-1336. [PMID: 28515110 DOI: 10.1158/1055-9965.epi-16-0786] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 02/24/2017] [Accepted: 05/04/2017] [Indexed: 11/16/2022] Open
Abstract
Background: Several studies suggest that test characteristics for the fecal immunochemical test (FIT) differ by gender, triggering a debate on whether men and women should be screened differently. We used the microsimulation model MISCAN-Colon to evaluate whether screening stratified by gender is cost-effective.Methods: We estimated gender-specific FIT characteristics based on first-round positivity and detection rates observed in a FIT screening pilot (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and costs of 480 gender-specific FIT screening strategies and compared them with uniform screening.Results: Biennial FIT screening from ages 50 to 75 was less effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY) gained, respectively] at higher costs (€42,161 vs. -€5,471, respectively). However, the incremental QALYs gained and costs of annual screening compared with biennial screening were more similar for both genders (8.7 QALYs gained and €26,394 for women vs. 6.7 QALYs gained and €20,863 for men). Considering all evaluated screening strategies, optimal gender-based screening yielded at most 7% more QALYs gained than optimal uniform screening and even resulted in equal costs and QALYs gained from a willingness-to-pay threshold of €1,300.Conclusions: FIT screening is less effective in women, but the incremental cost-effectiveness is similar in men and women. Consequently, screening stratified by gender is not more cost-effective than uniform FIT screening.Impact: Our conclusions support the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev; 26(8); 1328-36. ©2017 AACR.
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Affiliation(s)
| | - Atija Kapidzic
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Monique E van Leerdam
- Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
| | - Alex van der Steen
- Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, the Netherlands.,Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Harry J de Koning
- Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Lieke Hol
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, the Netherlands
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Blom J, Törnberg S. Interval cancers in a guaiac-based colorectal cancer screening programme: Consequences on sensitivity. J Med Screen 2017; 24:146-152. [DOI: 10.1177/0969141316682983] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Objective To evaluate interval cancers in the population-based colorectal cancer screening programme of Stockholm/Gotland, Sweden. Methods From 2008, individuals aged 60–69 were invited to colorectal cancer screening using biennial guaiac-based faecal occult blood test (Hemoccult®). Interval cancers, defined as colorectal cancer among participants not diagnosed by the screening programme but registered in the Swedish cancer register, were evaluated by cross-checking the screening histories for all cancers in the region 2008–2012. Results Of 203,848 individuals from nine different birth cohorts who participated (∼60%), 4530 (2.2%) tested positive. All invited individuals were followed up for 24 months after invitation. The cancer register reported 557 colorectal cancer, 219 (39.3%) screen-detected cancers and 338 (60.7%) interval cancers, generating both test- and episode sensitivities of approximately 40% and an interval cancer-rate of 17.1/10,000 tests. Among individuals with positive tests without colorectal cancer diagnosed at work-up colonoscopy, 37 interval cancers (10.9%) occurred. There was statistically significant lower sensitivity in women, ranging 22.4–32.2%, compared with 43.2–52.0% in men. Age-group and tumour location were not strongly correlated to screen-detected cancer rates. The programme sensitivity increased by year (20.3–25.0%), with successively more colorectal cancers diagnosed within the expanding programme (11.6–16.2%). Conclusion Interval cancer is a quality indicator of a screening programme. As the interval cancer-rate determined in a well-organized population-based screening programme was actually higher than the screen-detected cancer rate, a change to a more sensitive screening test is indicated. The lower screen-detected cancers among women, and compliance and quality of work-up colonoscopies also need attention.
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Affiliation(s)
- Johannes Blom
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Sven Törnberg
- Department of Oncology–Pathology, Karolinska Institutet and Regional Cancer Centre Stockholm Gotland, Stockholm, Sweden
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Wieten E, Schreuders EH, Nieuwenburg SAV, Hansen BE, Lansdorp-Vogelaar I, Kuipers EJ, Bruno MJ, Spaander MCW. Effects of Increasing Screening Age and Fecal Hemoglobin Cutoff Concentrations in a Colorectal Cancer Screening Program. Clin Gastroenterol Hepatol 2016; 14:1771-1777. [PMID: 27567693 DOI: 10.1016/j.cgh.2016.08.016] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 07/25/2016] [Accepted: 08/04/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Several countries have implemented programs to screen for colorectal cancer (CRC) by using the fecal immunochemical test (FIT). These programs vary considerably in age of the population screened and the cutoff concentration of fecal hemoglobin (Hb) used to identify candidates for further evaluation; these variations are usually based on a country's colonoscopy resources. We calculated how increasing the Hb cutoff concentration and screening age affects colonoscopy yield, missed lesions, and demand. METHODS We collected data from 10,008 average-risk individuals in The Netherlands, 50-74 years old, who were invited for an FIT in the first round of a population-based CRC screening program from November 2006 through December 2008. Fecal samples were collected, and levels of Hb were measured by using the OC-sensor Micro analyzer; concentrations ≥10 μg Hb/g feces were considered positive. Subjects with a positive FIT were scheduled for colonoscopy within 4 weeks. Logistic regression analysis was performed to evaluate the association between age and detection of advanced neoplasia. RESULTS In total, 5986 individuals (62%) participated in the study; 503 (8.4%) had a positive test result. Attendance, positive test results, detection of advanced neoplasia, and the FIT's positive predictive value all increased significantly with age (P < .001). Detection of advanced neoplasia ranged from 1.3% in the youngest age group to 6.2% in the oldest group; the positive predictive value of the FIT was 26% in the youngest group and 47% in the oldest group. Increasing the starting age of invitees from 50-74 years to 55-74 years reduced the proportion of subjects who underwent colonoscopy evaluation by 14% and resulted in 9% more subjects with advanced neoplasia being missed. Increasing the cutoff concentration from 10 to 15 μg Hb/g feces reduced the proportion of subjects who underwent colonoscopy evaluation by 11% and resulted in 6% of advanced neoplasia being missed. CONCLUSIONS In an analysis of an average-risk screening population in The Netherlands, we found that detection of advanced neoplasia by FIT increases significantly with age and fecal Hb cutoff concentration. Increasing the cutoff concentration or screening age reduces the numbers of patients who undergo colonoscopy evaluation in FIT-based CRC screening programs. Our findings provide insight in these effects per age category and cutoff concentration and the consequences in terms of missed lesions.
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Affiliation(s)
- Els Wieten
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Eline H Schreuders
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Stella A V Nieuwenburg
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
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Comparison of the yield from two faecal immunochemical tests at identical cutoff concentrations - a randomized trial in Latvia. Eur J Gastroenterol Hepatol 2016; 28:904-10. [PMID: 27120388 DOI: 10.1097/meg.0000000000000650] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE We have compared the performance of two faecal immunochemical tests (FIT) in an average-risk population. MATERIALS AND METHODS Altogether, 10 000 individuals aged 50-74 were selected randomly from the population of Latvia in 2011 and assigned randomly either to OC-Sensor or to FOB Gold single-time testing. Positivity of the test, frequency of colonic lesions, number needed to screen (NNscreen) and scope for the detection of an advanced neoplasm (cancer and advanced adenoma) were compared between the tests using the same cutoff concentrations in µg/g faeces. Confidence intervals (CIs) at 95% were calculated. RESULTS Positivity with the cutoff set at 10 µg/g faeces was 12.8% (95% CI: 11.4-14.2) for FOB Gold and 8.3% (95% CI: 7.2-9.4) for OC-Sensor (P<0.001). Positivity was higher in men and the older age groups. Colonoscopy compliance was 55.5%. There was no significant difference between the two tests at comparable cutoff concentrations in µg/g, colonoscopy attendance rate or colonoscopy results. For advanced neoplasm detection, there was no significant difference in number needed to scope and NNscreen at a cutoff of 10 µg/g faeces; however, lower NNscreen was required to detect advanced neoplasms with the FOB Gold test at increased cutoff concentrations. CONCLUSION Different quantitative FIT systems may report different positivity rate at identical cutoff concentrations, which has to be considered when implementing the use of FIT in national screening programmes.
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Grobbee EJ, Wieten E, Hansen BE, Stoop EM, de Wijkerslooth TR, Lansdorp-Vogelaar I, Bossuyt PM, Dekker E, Kuipers EJ, Spaander MC. Fecal immunochemical test-based colorectal cancer screening: The gender dilemma. United European Gastroenterol J 2016; 5:448-454. [PMID: 28507758 DOI: 10.1177/2050640616659998] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 06/01/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Despite differences between men and women in incidence of colorectal cancer (CRC) and its precursors, screening programs consistently use the same strategy for both genders. OBJECTIVE The objective of this article is to illustrate the effects of gender-tailored screening, including the effects on miss rates of advanced neoplasia (AN). METHODS Participants (age 50-75 years) in a colonoscopy screening program were asked to complete a fecal immunochemical test (FIT) before colonoscopy. Positivity rates, sensitivity and specificity for detection of AN at multiple cut-offs were determined. Absolute numbers of detected and missed AN per 1000 screenees were calculated. RESULTS In total 1,256 individuals underwent FIT and colonoscopy, 51% male (median age 61 years; IQR 56-66) and 49% female (median age 60 years; IQR 55-65). At all cut-offs men had higher positivity rates than women, ranging from 3.8% to 10.8% versus 3.2% to 4.8%. Sensitivity for AN was higher in men than women; 40%-25% and 35%-22%, respectively. More AN were found and missed in absolute numbers in men at all cut-offs. CONCLUSION More AN were both detected and missed in men compared to women at all cut-offs. Gender-tailored cut-offs could either level sensitivity in men and women (i.e., lower cut-off in women) or level the amount of missed lesions (i.e., lower cut-off in men).
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Affiliation(s)
- Esmée J Grobbee
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Els Wieten
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Esther M Stoop
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Thomas R de Wijkerslooth
- Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Patrick M Bossuyt
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Manon Cw Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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Alvarez-Urturi C, Andreu M, Hernandez C, Perez-Riquelme F, Carballo F, Ono A, Cruzado J, Cubiella J, Hernandez V, Mao CG, Perez E, Salas D, Andrés M, Bujanda L, Portillo I, Sarasqueta C, Quintero E, Morillas JD, Lanas A, Sostres C, Augé JM, Castells A, Bessa X. Impact of age- and gender-specific cut-off values for the fecal immunochemical test for hemoglobin in colorectal cancer screening. Dig Liver Dis 2016; 48:542-551. [PMID: 26936343 DOI: 10.1016/j.dld.2016.02.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2015] [Revised: 01/15/2016] [Accepted: 02/01/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is no information on the impact of age and gender on the diagnostic yield of different positivity thresholds for the fecal immunochemical test for hemoglobin (FIT). OBJECTIVES To evaluate the performance of this test at distinct positivity cut-offs in a population-based colorectal cancer (CRC) screening program. METHODS CRC detection rate (DR), and analysis of resources were evaluated retrospectively, at different cut-offs of FIT (20, 25, 30, 35 and 40μg Hb/g) respect to a reference value (15μg Hb/g), according to age and gender, in a screening population of 10,611 participants of the ColonPrev study (Quintero. NEJM 2013). RESULTS At the reference cut-off value, 36 CRC and 252 advanced adenomas (AA) were diagnosed. Increasing the cut-off in women ≤60 years decreases colonoscopies performed by 44.5% without modifying the CRC (DR). Same CRC DR was observed in men ≤60 years and women >60 years increasing cut-off at 25-30μg Hb/g. In men >60 years, all increases in the cut-off affected the CRC DR, especially when the cut-off was increased from 35 to 40μg Hb/g (CRC miss rate 25%). CONCLUSIONS To improve the performance of FIT in CRC screening programs, FIT cut-offs could be individualized by age and gender.
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Affiliation(s)
- Cristina Alvarez-Urturi
- Department of Gastroenterology, Hospital del Mar, Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Autonomous University of Barcelona and Pompeu Fabra University, Barcelona, Catalonia, Spain
| | - Montserrat Andreu
- Department of Gastroenterology, Hospital del Mar, Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Autonomous University of Barcelona and Pompeu Fabra University, Barcelona, Catalonia, Spain
| | - Cristina Hernandez
- Department of Epidemiology and Evaluation, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Catalonia, Spain
| | - Francisco Perez-Riquelme
- Colorectal Cancer Prevention Program of Murcia, Dirección General de Salud Pública, Consejería de Sanidad y Política Social, Murcia, Spain
| | - Fernando Carballo
- Colorectal Cancer Prevention Program of Murcia, Dirección General de Salud Pública, Consejería de Sanidad y Política Social, Murcia, Spain
| | - Akiko Ono
- Colorectal Cancer Prevention Program of Murcia, Dirección General de Salud Pública, Consejería de Sanidad y Política Social, Murcia, Spain
| | - Jose Cruzado
- Colorectal Cancer Prevention Program of Murcia, Dirección General de Salud Pública, Consejería de Sanidad y Política Social, Murcia, Spain
| | - Joaquín Cubiella
- Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, IBIV - Institute of Biomedical Research of Vigo, Vigo, Spain
| | - Vicent Hernandez
- Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, IBIV - Institute of Biomedical Research of Vigo, Vigo, Spain
| | | | - Elena Perez
- Colorectal Cancer Screening Program, Dirección General de Salud Pública, València, Spain
| | - Dolores Salas
- Colorectal Cancer Screening Program, Dirección General de Salud Pública, València, Spain
| | - Mercedes Andrés
- Colorectal Cancer Screening Program, Dirección General de Salud Pública, València, Spain
| | - Luis Bujanda
- Department of Gastroenterology, Donostia Hospital-Instituto Biodonostia, CIBERehd, University of Basque Country (UPV/EHU), San Sebastián, Spain
| | - Isabel Portillo
- Centro Coordinador del Programa de Cribado Cáncer Colorrectal, Organización Central de Osakidetza-Servicio Vasco de Salud, San Sebastián, Spain
| | - Cristina Sarasqueta
- Hospital Donostia, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), San Sebastián, Spain
| | - Enrique Quintero
- Department of Gastroenterology, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
| | | | - Angel Lanas
- Department of Gastroenterology, University of Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain
| | - Carlos Sostres
- Department of Gastroenterology, University of Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain
| | - Josep Maria Augé
- Department of Biochemistry and Molecular Genetics, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain
| | - Antoni Castells
- Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain
| | - Xavier Bessa
- Department of Gastroenterology, Hospital del Mar, Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Autonomous University of Barcelona and Pompeu Fabra University, Barcelona, Catalonia, Spain.
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Baxter NT, Ruffin MT, Rogers MAM, Schloss PD. Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions. Genome Med 2016; 8:37. [PMID: 27056827 PMCID: PMC4823848 DOI: 10.1186/s13073-016-0290-3] [Citation(s) in RCA: 218] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 03/16/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90% chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT). METHODS We sequenced the 16S rRNA genes from the stool samples of 490 patients. We used the relative abundances of the bacterial populations within each sample to develop a random forest classification model that detects colonic lesions using the relative abundance of gut microbiota and the concentration of hemoglobin in stool. RESULTS The microbiota-based random forest model detected 91.7% of cancers and 45.5% of adenomas while FIT alone detected 75.0% and 15.7%, respectively. Of the colonic lesions missed by FIT, the model detected 70.0% of cancers and 37.7% of adenomas. We confirmed known associations of Porphyromonas assaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, and Fusobacterium nucleatum with CRC. Yet, we found that the loss of potentially beneficial organisms, such as members of the Lachnospiraceae, was more predictive for identifying patients with adenomas when used in combination with FIT. CONCLUSIONS These findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.
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Affiliation(s)
- Nielson T. Baxter
- />Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI USA
| | - Mack T. Ruffin
- />Department of Family Medicine, University of Michigan, Ann Arbor, MI USA
| | - Mary A. M. Rogers
- />Department of Internal Medicine, University of Michigan, Ann Arbor, MI USA
| | - Patrick D. Schloss
- />Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI USA
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Abstract
Colorectal cancer (CRC) forms an important public health problem, especially in developed countries. CRC screening tests can be used to identify asymptomatic individuals with CRC precursors and (early) cancer. Removal of these lesions reduces CRC incidence and prevents CRC-related mortality. There are a range of screening tests available, each with advantages and disadvantages. Stool screening tests can broadly be divided into fecal occult blood tests (FOBTs) and molecular biomarker test, such as DNA/RNA marker tests, protein markers, and fecal microbiome marker tests. Guaiac fecal occult blood tests (gFOBT) have been demonstrated in large randomized screening trials to reduce CRC mortality. Fecal immunochemical tests (FIT) have superior adherence, usability, and accuracy as compared to gFOBT. Advantage of the use of quantitative FITs in CRC screening programs is the cut-off level that can be adjusted. Molecular biomarker DNA tests have shown to detect significantly more cancers than FIT. By combining biomarker DNA tests with FIT, sensitivity for advanced adenomas can be increased significantly. However, it has lower specificity thus demands more colonoscopy resources, is more cumbersome, and costly. The adherence has not been assessed in population screening trials. For these reasons, FIT is therefore at present regarded as the preferred method of non-invasive CRC screening. This chapter will review the current status of fecal test-based CRC screening.
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Correlating Quantitative Fecal Immunochemical Test Results with Neoplastic Findings on Colonoscopy in a Population-Based Colorectal Cancer Screening Program: A Prospective Study. Can J Gastroenterol Hepatol 2016; 2016:4650471. [PMID: 28116286 PMCID: PMC5220421 DOI: 10.1155/2016/4650471] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 11/06/2016] [Accepted: 11/09/2016] [Indexed: 02/06/2023] Open
Abstract
Background and Aims. The Canadian Partnership Against Cancer (CPAC) recommends a fecal immunochemical test- (FIT-) positive predictive value (PPV) for all adenomas of ≥50%. We sought to assess FIT performance among average-risk participants of the British Columbia Colon Screening Program (BCCSP). Methods. From Nov-2013 to Dec-2014 consecutive participants of the BCCSP were assessed. Data was obtained from a prospectively collected database. A single quantitative FIT (NS-Plus, Alfresa Pharma Corporation, Japan) with a cut-off of ≥10 μg/g (≥50 ng/mL) was used. Results. 20,322 FIT-positive participants underwent CSPY. At a FIT cut-off of ≥10 μg/g (≥50 ng/mL) the PPV for all adenomas was 52.0%. Increasing the FIT cut-off to ≥20 μg/g (≥100 ng/mL) would increase the PPV for colorectal cancer (CRC) by 1.5% and for high-risk adenomas (HRAs) by 6.5% at a cost of missing 13.6% of CRCs and 32.4% of HRAs. Conclusions. As the NS-Plus FIT cut-off rises, the PPV for CRC and HRAs increases but at the cost of missed lesions. A cut-off of ≥10 μg/g (≥50 ng/mL) produces a PPV for all adenomas exceeding national recommendations. Health authorities need to take into consideration endoscopic resources when selecting a FIT positivity threshold.
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