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Young GP, Senore C, Schoengold R, Laven-Law G, Saito H, Symonds EL. An Adjustable Positivity Threshold for Non-invasive Screening Tests for Colorectal Neoplasms Can Improve Screening Program Effectiveness and Feasibility. Dig Dis Sci 2024:10.1007/s10620-024-08657-6. [PMID: 39384709 DOI: 10.1007/s10620-024-08657-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 09/19/2024] [Indexed: 10/11/2024]
Abstract
BACKGROUND In two-step population screening for colorectal cancer (CRC), a simple non-invasive test, commonly a fecal immunochemical test for hemoglobin (FIT), is first undertaken to predict, based on the fecal hemoglobin concentration (f-Hb), who is more likely to have colorectal neoplasia and needs colonoscopy. AIM To evaluate the importance of being able to adjust the f-Hb threshold that triggers follow-up colonoscopy (the "positivity threshold"), we evaluated the predictive value of f-Hb for colorectal neoplasia and its implications for the configuration of new non-invasive tests. METHODS A literature review was conducted on the use of quantitative FIT to select the positivity threshold, followed by using f-Hb from a large population to model how adjusting the positivity threshold enabled achievement of the desired program outcomes in a feasible manner. RESULTS The literature review and the modeling found that while the f-Hb positivity threshold is predictive for colorectal neoplasia across a wide range of f-Hb, there is a complex relationship between program outcomes and f-Hb. The threshold determines not just clinical accuracy (including true- and false-positive results for CRC and/or advanced precursor lesions), but also the colonoscopy workload. A lower f-Hb threshold is associated with a higher sensitivity for neoplasia but a lower specificity and a heavier load of follow-up colonoscopies. Consequently, the threshold determines a program's impact on population CRC mortality and incidence, but also its feasibility and cost-effectiveness within a health-care system. DISCUSSION We are entering a new era of non-invasive screening tests, where multiple biomarkers found in biological samples such as blood as well as feces, are being developed and evaluated. These typically specify a non-transparent algorithm, developed with machine learning, to provide a predictive dichotomous positive/negative result with a fixed associated clinical accuracy and colonoscopy workload. This will restrict use of new tests in jurisdictions where the accuracy and workload implications do not match the desired screening program outcomes. CONCLUSION However, similar to flexible FIT positivity thresholds, it would be ideal if new tests also provide capacity for screening program providers to select the positivity threshold that delivers their desired screening outcomes in a feasible manner. How marketing, distribution and reimbursement of non-invasive tests are approved, funded and implemented varies widely across jurisdictions and must be taken into account.
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Affiliation(s)
- Graeme P Young
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia.
| | - Carlo Senore
- University hospital Città della salute e della Scienza, Turin, Italy
| | | | - Geri Laven-Law
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia
| | | | - Erin L Symonds
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia
- Bowel Health Service, Flinders Medical Centre, Adelaide, SA, Australia
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Pluimers SJKF, Wisse PHA, van Leerdam ME, Dekker E, van Lansdorp-Vogelaar I, Tanis PJ, Elferink MAG, den Hoed CM, Spaander MCW. Risk of Recurrence in Screen-Detected vs Non-Screen-Detected Colorectal Cancer Patients. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00861-9. [PMID: 39326582 DOI: 10.1016/j.cgh.2024.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 07/18/2024] [Accepted: 08/20/2024] [Indexed: 09/28/2024]
Abstract
BACKGROUND AND AIMS Patients with screen-detected colorectal cancer (CRC) have a better stage-specific overall survival than non-screen-detected CRC. Currently, it is unknown if recurrence rates differ between screen-detected and non-screen-detected CRCs, and whether this could explain the observed difference in overall survival. Therefore, we aimed to assess the disease-free survival (DFS) rates in screen-detected and non-screen-detected CRCs and if recurrence affects overall survival. METHODS Dutch CRC (stage I-III) patients, diagnosed by screening or not in the first 6 months of 2015, were included from the Netherlands Cancer Registry. DFS and survival data were retrieved and analyzed by Kaplan-Meier method. The association between mode of detection and recurrence and overall survival was evaluated with a Cox regression model. RESULTS A total of 3725 CRC patients were included, 2073 (55.7%) non-screen detected and 1652 (44.3%) screen detected. Three-year DFS was significantly higher in screen-detected CRC compared with non-screen-detected CRC (87.8% vs 77.2%; P < .001). Stage-specific DFS rates for screen-detected vs non-screen-detected CRC were 94.7% vs 92.3% for stage I (P = .45), 84.3% vs 81.4% for stage II (P = .17), and 77.9% vs 66.7% for stage III (P < .001), respectively. Detection by screening was independently associated with a lower risk of recurrence (hazard ratio, 0.67; 95% confidence interval, 0.55-0.81; P < .001) when adjusted for age, sex, tumor location, stage and treatment. Recurrence independently predicted overall survival (hazard ratio, 15.90; 95% confidence interval, 13.28-19.04; P < .001). CONCLUSION DFS was significantly better in screen-detected compared with non-screen-detected CRCs independent of age, sex, tumor location, stage and treatment, and was associated with an overall survival benefit.
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Affiliation(s)
- Sanne J K F Pluimers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Pieter H A Wisse
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, the Netherlands
| | - Evelien Dekker
- Departement of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, the Netherlands
| | | | - Pieter J Tanis
- Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Marloes A G Elferink
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Caroline M den Hoed
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
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Luu XQ, Lee K, Jun JK, Suh M, Jung KW, Choi KS. Effect of colorectal cancer screening on long-term survival of colorectal cancer patients: Results of the Korea National Cancer Screening Program. Int J Cancer 2022; 150:1958-1967. [PMID: 35099813 DOI: 10.1002/ijc.33953] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/27/2021] [Accepted: 01/13/2022] [Indexed: 11/08/2022]
Abstract
The Korea National Cancer Screening Program (KNCSP) provides fecal immunochemical test-based colorectal cancer (CRC) screening for people aged ≥50 years. This study aimed to investigate the long-term survival effects of CRC screening based on screening history and interval time since screening. The study cohort was obtained by linking three national databases, namely the Korea Central Cancer Registry, KNCSP database, and Death Certificate. We included 32 509 CRC patients diagnosed in 2008-2009, who underwent CRC screening via the KNCSP between 2004 and 2009. The patients were followed-up until 2019, and their survival was assessed according to their CRC screening history. Cox proportional hazards regression was used to compare time to deaths among CRC patients according to CRC screening history, after adjusting for covariates. Of the 32 509 patients, 20 022 (61.5%) patients were alive by the end of 2019. Long-term survival was significantly higher among screened patients (68.2%) than non-screened (57.2%) individuals. Compared with never-screened patients, the hazard ratio (HR) for CRC-specific death in screened patients was 0.77 (95% CI%, 0.73-0.80). Lowest HR was observed in screened, localized CRC patients (HR, 0.48; 95% CI, 0.42-0.56); HR for CRC-specific death was the lowest in patients screened within 12 months of diagnosis (HR, 0.70; 95% CI, 0.66-0.74), following which, the HRs increased with increasing time interval. CRC screening was positively associated with favorable prognosis in CRC patients aged 50-79 years. The effects on long-term survival according to interval time was the best among individuals screened within one year before diagnosis. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Xuan Quy Luu
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea
| | - Kyeongmin Lee
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea
| | - Jae Kwan Jun
- National Cancer Control Institute, National Cancer Center, Goyang, South Korea
| | - Mina Suh
- National Cancer Control Institute, National Cancer Center, Goyang, South Korea
| | - Kyu-Won Jung
- National Cancer Control Institute, National Cancer Center, Goyang, South Korea
| | - Kui Son Choi
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea
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Ray T, Ryusaki T, Ray PS. Therapeutically Targeting Cancers That Overexpress FOXC1: A Transcriptional Driver of Cell Plasticity, Partial EMT, and Cancer Metastasis. Front Oncol 2021; 11:721959. [PMID: 34540690 PMCID: PMC8446626 DOI: 10.3389/fonc.2021.721959] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 07/15/2021] [Indexed: 12/28/2022] Open
Abstract
Metastasis accounts for more than 90% of cancer related mortality, thus the most pressing need in the field of oncology today is the ability to accurately predict future onset of metastatic disease, ideally at the time of initial diagnosis. As opposed to current practice, what would be desirable is that prognostic, biomarker-based detection of metastatic propensity and heightened risk of cancer recurrence be performed long before overt metastasis has set in. Without such timely information it will be impossible to formulate a rational therapeutic treatment plan to favorably alter the trajectory of disease progression. In order to help inform rational selection of targeted therapeutics, any recurrence/metastasis risk prediction strategy must occur with the paired identification of novel prognostic biomarkers and their underlying molecular regulatory mechanisms that help drive cancer recurrence/metastasis (i.e. recurrence biomarkers). Traditional clinical factors alone (such as TNM staging criteria) are no longer adequately prognostic for this purpose in the current molecular era. FOXC1 is a pivotal transcription factor that has been functionally implicated to drive cancer metastasis and has been demonstrated to be an independent predictor of heightened metastatic risk, at the time of initial diagnosis. In this review, we present our viewpoints on the master regulatory role that FOXC1 plays in mediating cancer stem cell traits that include cellular plasticity, partial EMT, treatment resistance, cancer invasion and cancer migration during cancer progression and metastasis. We also highlight potential therapeutic strategies to target cancers that are, or have evolved to become, “transcriptionally addicted” to FOXC1. The potential role of FOXC1 expression status in predicting the efficacy of these identified therapeutic approaches merits evaluation in clinical trials.
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Affiliation(s)
- Tania Ray
- R&D Division, Onconostic Technologies (OT), Inc., Champaign, IL, United States
| | | | - Partha S Ray
- R&D Division, Onconostic Technologies (OT), Inc., Champaign, IL, United States
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Biological and prognostic differences between symptomatic colorectal carcinomas and those detected by screening. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2019; 45:1876-1881. [PMID: 31189513 DOI: 10.1016/j.ejso.2019.05.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 05/16/2019] [Accepted: 05/23/2019] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening. STUDY METHOD A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained. RESULTS A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms. CONCLUSIONS The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.
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Díaz-Tasende J. Colorectal cancer screening and survival. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:681-683. [PMID: 30284905 DOI: 10.17235/reed.2018.5870/2018] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
It is difficult to resist the undeniable allure of screening as a means to diagnose common, potentially serious diseases before their natural history reaches an incurable stage. Colorectal cancer (CRC) is a classical example where the benefits seem to be within reach: we have technologies available that allow its diagnosis before symptoms or signs develop, at a reasonable cost, and using methods acceptable by a significant percentage of the population.
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Affiliation(s)
- José Díaz-Tasende
- Servicio de Medicina del Aparato Digestivo, Hospital Universitario 12 de Octubre, España
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Caspersen M, Sørensen N, Schrohl A, Iversen P, Nielsen H, Brünner N. Investigation of Tissue Inhibitor of Metalloproteinases 1 in Plasma from Colorectal Cancer Patients and Blood Donors by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Int J Biol Markers 2018. [DOI: 10.1177/172460080702200213] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Early detection of colorectal cancer (CRC) improves patient survival. Plasma tissue inhibitor of metalloproteinases 1 (TIMP-1) measurements by enzyme-linked immunosorbent assay (ELISA) have been suggested as a new method for the early detection of CRC. To further investigate the nature of TIMP-1 in plasma, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS) was used. TIMP-1 measurements of plasma from 16 healthy donors and 14 CRC patients were performed using TIMP-1 monoclonal antibody in SELDI TOF MS and ELISA. SELDI TOF MS applying an antibody to TIMP-1 revealed that human plasma TIMP-1 has a mass of 25.1 kDa and exhibits several isoforms. Both methods showed increased plasma TIMP-1 values for cancer patients as compared to healthy individuals. The p values for the separation of the groups were 0.0019 for ELISA and <0.0001 for SELDI TOF MS. CRC did not fundamentally affect the appearance of TIMP-1 as evaluated by SELDI TOF MS.
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Affiliation(s)
- M.B. Caspersen
- Ciphergen Biosystems, Copenhagen, Faculty of Life Sciences, University of Copenhagen, Frederiksberg
| | - N.M. Sørensen
- Department of Veterinary Rathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg
| | - A.S. Schrohl
- Department of Veterinary Rathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg
| | - P. Iversen
- Ciphergen Biosystems, Copenhagen, Faculty of Life Sciences, University of Copenhagen, Frederiksberg
| | - H.J. Nielsen
- Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre - Denmark
| | - N. Brünner
- Department of Veterinary Rathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg
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van der Meulen MP, Lansdorp-Vogelaar I, Goede SL, Kuipers EJ, Dekker E, Stoker J, van Ballegooijen M. Colorectal Cancer: Cost-effectiveness of Colonoscopy versus CT Colonography Screening with Participation Rates and Costs. Radiology 2018; 287:901-911. [PMID: 29485322 DOI: 10.1148/radiol.2017162359] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Purpose To compare the cost-effectiveness of computed tomographic (CT) colonography and colonoscopy screening by using data on unit costs and participation rates from a randomized controlled screening trial in a dedicated screening setting. Materials and Methods Observed participation rates and screening costs from the Colonoscopy or Colonography for Screening, or COCOS, trial were used in a microsimulation model to estimate costs and quality-adjusted life-years (QALYs) gained with colonoscopy and CT colonography screening. For both tests, the authors determined optimal age range and screening interval combinations assuming a 100% participation rate. Assuming observed participation for these combinations, the cost-effectiveness of both tests was compared. Extracolonic findings were not included because long-term follow-up data are lacking. Results The participation rates for colonoscopy and CT colonography were 21.5% (1276 of 5924 invitees) and 33.6% (982 of 2920 invitees), respectively. Colonoscopy was more cost-effective in the screening strategies with one or two lifetime screenings, whereas CT colonography was more cost-effective in strategies with more lifetime screenings. CT colonography was the preferred test for willingness-to-pay-thresholds of €3200 per QALY gained and higher, which is lower than the Dutch willingness-to-pay threshold of €20 000. With equal participation, colonoscopy was the preferred test independent of willingness-to-pay thresholds. The findings were robust for most of the sensitivity analyses, except with regard to relative screening costs and subsequent participation. Conclusion Because of the higher participation rates, CT colonography screening for colorectal cancer is more cost-effective than colonoscopy screening. The implementation of CT colonography screening requires previous satisfactory resolution to the question as to how best to deal with extracolonic findings. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Miriam P van der Meulen
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - Iris Lansdorp-Vogelaar
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - S Lucas Goede
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - Ernst J Kuipers
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - Evelien Dekker
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - Jaap Stoker
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
| | - Marjolein van Ballegooijen
- From the Departments of Public Health (M.P.v.d.M., I.L.V., S.L.G., M.v.B.), Gastroenterology and Hepatology (E.J.K.), and Internal Medicine (E.J.K.), Erasmus Medical Centre, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands; Department of Gastroenterology and Hepatology (E.D.) and Department of Radiology (J.S.), Academic Medical Center, Amsterdam, the Netherlands
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Brenner H, Jansen L, Ulrich A, Chang-Claude J, Hoffmeister M. Survival of patients with symptom- and screening-detected colorectal cancer. Oncotarget 2018; 7:44695-44704. [PMID: 27213584 PMCID: PMC5190129 DOI: 10.18632/oncotarget.9412] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 04/26/2016] [Indexed: 12/23/2022] Open
Abstract
Background An increasing proportion of colorectal cancer (CRC) patients are diagnosed by screening rather than symptoms. Aims We aimed to assess and compare prognosis of patients with screen-detected CRC and symptom-detected CRC. Methods Overall and CRC specific mortality over a median follow-up of 4.8 years was assessed according to mode of diagnosis (symptoms, screening colonoscopy, fecal occult blood test [FOBT], other) in a multi-center cohort of 2,450 CRC patients aged 50-79 years recruited in Germany in 2003-2010. Results 68%, 11% and 10% were detected by symptoms, screening colonoscopy and FOBT, respectively. The screen-detected cancers had a more favorable stage distribution than the symptom-detected cancers (68% versus 50% in stage I or II). Age- and sex adjusted hazard ratios (HRs) of total mortality with 95% confidence intervals (95% CIs) compared to symptom-detected cancers were 0.35 (0.24-0.50) and 0.36 (0.25-0.53) for screening colonoscopy and FOBT detected CRCs, respectively. HRs were only slightly attenuated and remained highly significant after adjustment for stage and multiple other covariates (0.50 (0.34-0.73) and 0.54 (0.37-0.80), respectively). Even stronger associations were seen for CRC specific mortality. Patients with screen-detected stage III CRC had as good CRC specific survival as patients with symptom-detected stage I or II CRC. Conclusions Patients with screen-detected CRC have a very good prognosis far beyond the level explained by their more favorable stage distribution. Mode of detection is an important, easy-to-obtain proxy indicator for favorable diagnosis beyond earlier stage at diagnosis and as such may be useful for risk stratification in treatment decisions.
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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), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alexis Ulrich
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Jenny Chang-Claude
- Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Greuter MJE, Berkhof J, Fijneman RJA, Demirel E, Lew JB, Meijer GA, Stoker J, Coupé VMH. The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis. Br J Radiol 2016; 89:20150910. [PMID: 27194458 DOI: 10.1259/bjr.20150910] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. METHODS We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. RESULTS The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were €60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. CONCLUSION CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. ADVANCES IN KNOWLEDGE This is the first study to assess the cost-effectiveness of MRC screening for CRC.
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Affiliation(s)
- Marjolein J E Greuter
- 1 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands
| | - Johannes Berkhof
- 1 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands
| | - Remond J A Fijneman
- 2 Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Erhan Demirel
- 1 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands
| | - Jie-Bin Lew
- 3 Cancer Research Division, Cancer Council NSW, NSW, Australia
| | - Gerrit A Meijer
- 2 Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Jaap Stoker
- 4 Department of Radiology, Academic Medical Center, Amsterdam, Netherlands
| | - Veerle M H Coupé
- 1 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands
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Greuter MJE, Demirel E, Lew JB, Berkhof J, Xu XM, Canfell K, Dekker E, Meijer GA, Coupé VMH. Long-Term Impact of the Dutch Colorectal Cancer Screening Program on Cancer Incidence and Mortality-Model-Based Exploration of the Serrated Pathway. Cancer Epidemiol Biomarkers Prev 2015; 25:135-44. [PMID: 26598535 DOI: 10.1158/1055-9965.epi-15-0592] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 10/28/2015] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND We aimed to predict the long-term colorectal cancer incidence, mortality, and colonoscopy demand of the recently implemented Dutch colorectal cancer screening program. METHODS The Adenoma and Serrated pathway to Colorectal Cancer model was set up to simulate the Dutch screening program consisting of biennial fecal immunochemical testing combined with the new Dutch surveillance guidelines, between 2014 and 2044. The impact of screening and surveillance was evaluated under three sets of natural history assumptions differing in the contribution of the serrated pathway to colorectal cancer incidence. In sensitivity analyses, other assumptions concerning the serrated pathway were varied. Model-predicted outcomes were yearly colorectal cancer incidence, mortality, and colonoscopy demand per year. RESULTS Assuming an aging population, colorectal cancer incidence under 30 years of screening is predicted to decrease by 35% and 31% for a contribution of 0% and 30% of the serrated pathway to colorectal cancer, respectively. For colorectal cancer mortality, reductions are 47% and 45%. In 2044, 110,000 colonoscopies will be required annually assuming no contribution of the serrated pathway (27 per 1,000 individuals in the screening age range). Including the serrated pathway influences predicted screening effectiveness if serrated lesions are neither detected nor treated at colonoscopy, and/or if colorectal cancers arising from serrated lesions have substantially lower survival rates than those arising from adenomas. CONCLUSIONS The Dutch screening program will markedly decrease colorectal cancer incidence and mortality but considerable colonoscopy resources will be required. IMPACT Predictions of long-term screening effectiveness are preferably based on both pathways to colorectal cancer to transparently describe the impact of uncertainties regarding the serrated pathway on long-term predictions.
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Affiliation(s)
- Marjolein J E Greuter
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
| | - Erhan Demirel
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
| | - Jie-Bin Lew
- Lowy Cancer Research Centre, The University of NSW, New South Wales, Australia. Lowy Cancer Research Centre, Prince of Wales Clinical School, The University of NSW, New South Wales, Australia
| | - Johannes Berkhof
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
| | - Xiang-Ming Xu
- Lowy Cancer Research Centre, The University of NSW, New South Wales, Australia. Lowy Cancer Research Centre, Prince of Wales Clinical School, The University of NSW, New South Wales, Australia
| | - Karen Canfell
- Lowy Cancer Research Centre, The University of NSW, New South Wales, Australia. Lowy Cancer Research Centre, Prince of Wales Clinical School, The University of NSW, New South Wales, Australia
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands
| | - Gerrit A Meijer
- Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
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Coldman AJ, Phillips N, Brisson J, Flanagan W, Wolfson M, Nadeau C, Fitzgerald N, Miller AB. Using the Cancer Risk Management Model to evaluate colorectal cancer screening options for Canada. ACTA ACUST UNITED AC 2015; 22:e41-50. [PMID: 25908920 DOI: 10.3747/co.22.2013] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Several screening methods for colorectal cancer (crc) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (fobt), the fecal immunochemical test (fit), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, crc cases and deaths prevented, and direct health system costs. METHODS A natural history model of crc was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (crmm) from the Canadian Partnership Against Cancer. The crmm-crc permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the crmm-crc to run 10 million replicate simulations. RESULTS Using base parameter values and some user-specified values in the crmm-crc, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from crc. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the fit were predicted to be the most effective. In sensitivity analyses performed for the fobt and fit screening strategies, fobt parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The fit was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold. CONCLUSIONS The crmm-crc provides a sophisticated and flexible environment in which to evaluate crc control options. All screening scenarios considered in this study effectively reduced crc mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters.
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Affiliation(s)
| | - N Phillips
- BC Cancer Research Centre, Vancouver, BC
| | - J Brisson
- Institute de Santé Publique, Quebec City, QC
| | | | | | | | - N Fitzgerald
- Canadian Partnership Against Cancer, Toronto, ON
| | - A B Miller
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON
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COST-EFFECTIVENESS OF AN ADVANCE NOTIFICATION LETTER TO INCREASE COLORECTAL CANCER SCREENING. Int J Technol Assess Health Care 2013; 29:261-8. [DOI: 10.1017/s0266462313000226] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Objectives:The aim of this study is to evaluate the cost-effectiveness of a patient-direct mailed advance notification letter on participants of a National Bowel Cancer Screening Program (NBCSP) in Australia, which was launched in August 2006 and offers free fecal occult blood testing to all Australians turning 50, 55, or 65 years of age in any given year.Methods:This study followed a hypothetical cohort of 50-year-old, 55-year-old, and 65-year-old patients undergoing fecal occult blood test (FOBT) screening through a decision analytic Markov model. The intervention compared two strategies: (i) advance letter, NBCSP, and FOBT compared with (ii) NBCSP and FOBT. The main outcome measures were life-years gained (LYG), quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio.Results:An advance notification screening letter would yield an additional 54 per 100,000 colorectal cancer deaths avoided compared with no letter. The estimated cost-effectiveness was $3,976 per LYG and $6,976 per QALY gained.Conclusions:An advance notification letter in the NBCSP may have a significant impact on LYG and cancer deaths avoided. It is cost-effective and offers a feasible strategy that could be rolled out across other screening program at an acceptable cost.
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Nielsen HJ, Brünner N, Frederiksen C, Lomholt AF, King D, Jørgensen LN, Olsen J, Rahr HB, Thygesen K, Hoyer U, Laurberg S, Christensen IJ. Plasma tissue inhibitor of metalloproteinases-1 (TIMP-1): a novel biological marker in the detection of primary colorectal cancer. Protocol outlines of the Danish-Australian endoscopy study group on colorectal cancer detection. Scand J Gastroenterol 2008; 43:242-8. [PMID: 18224568 DOI: 10.1080/00365520701523439] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Hans Jørgen Nielsen
- Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark.
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15
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The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Occult Blood Testing. POINT OF CARE 2007. [DOI: 10.1097/poc0b013e31809ff851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Caspersen MB, Sørensen NM, Schrohl AS, Iversen P, Nielsen HJ, Brünner N. Investigation of Tissue Inhibitor of Metalloproteinases 1 in Plasma from Colorectal Cancer Patients and Blood Donors by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Int J Biol Markers 2007; 22:89-94. [PMID: 17549663 DOI: 10.1177/172460080702200201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Early detection of colorectal cancer (CRC) improves patient survival. Plasma tissue inhibitor of metalloproteinases 1 (TIMP-1) measurements by enzyme-linked immunosorbent assay (ELISA) have been suggested as a new method for the early detection of CRC. To further investigate the nature of TIMP-1 in plasma, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS) was used. TIMP-1 measurements of plasma from 16 healthy donors and 14 CRC patients were performed using TIMP-1 monoclonal antibody in SELDI TOF MS and ELISA. SELDI TOF MS applying an antibody to TIMP-1 revealed that human plasma TIMP-1 has a mass of 25.1 kDa and exhibits several isoforms. Both methods showed increased plasma TIMP-1 values for cancer patients as compared to healthy individuals. The p values for the separation of the groups were 0.0019 for ELISA and <0.0001 for SELDI TOF MS. CRC did not fundamentally affect the appearance of TIMP-1 as evaluated by SELDI TOF MS.
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Maciosek MV, Solberg LI, Coffield AB, Edwards NM, Goodman MJ. Colorectal cancer screening: health impact and cost effectiveness. Am J Prev Med 2006; 31:80-9. [PMID: 16777546 DOI: 10.1016/j.amepre.2006.03.009] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2005] [Revised: 03/15/2006] [Accepted: 03/17/2006] [Indexed: 01/28/2023]
Abstract
BACKGROUND Colorectal cancer is the second leading cause of cancer-related death in the United States, yet recommended screenings are not delivered to most people. This assessment of colorectal cancer screening's value to the U.S. population is part of the update to a 2001 ranking of recommended clinical preventive services found in the accompanying article. This article describes the burden of disease prevented and cost-effectiveness as a result of offering patients a choice of colorectal cancer screening tools. METHODS Methods used were designed to ensure consistent estimates across many services and are described in more detail in the companion articles. In a secondary analysis, the authors also estimated the impact of increasing offers for colorectal cancer screening above current levels among the current cross-section of adults aged 50 and older. RESULTS If a birth cohort of 4 million were offered screening at recommended intervals, 31,500 deaths would be prevented and 338,000 years of life would be gained over the lifetime of the birth cohort. In the current cross-section of people aged 50 and older, 18,800 deaths could be prevented each year by offering all people in this group screening at recommended intervals. Only 58% of these deaths are currently being prevented. In year 2000 dollars, the cost effectiveness of offering patients aged 50 and older a choice of colorectal cancer screening options is $11,900 per year of life gained. CONCLUSIONS Colorectal cancer screening is a high-impact, cost-effective service used by less than half of persons aged 50 and older.
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Kronborg O, Jørgensen OD, Fenger C, Rasmussen M. Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds. Scand J Gastroenterol 2004; 39:846-51. [PMID: 15513382 DOI: 10.1080/00365520410003182] [Citation(s) in RCA: 174] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Two large true population studies in Europe have shown a significant reduction in mortality from colorectal cancer (CRC) by screening with a faecal occult blood test. In one trial conducted in Funen County, 61,933 individuals (aged 45-75 years) were randomly allocated either to a control group or to receive a biennial Hemoccult-II test. METHODS These individuals were followed from 1985 to 2002 and 9 screening rounds were performed. RESULTS First screening was accepted by 67% (20,672). Positivity rates varied between 0.8% and 3.8%, and the cumulative proportion of the test group having colonoscopy was 5.3%. Screen-detected CRC was early (Dukes' A) in 36% compared to 11% among controls. Incidence of CRC was unchanged, but mortality was reduced by 11%. This figure increased to 43% in persons participating in all 9 rounds. No more than 8,558 were screened at the 9th round. Patients with CRC detected between screenings had better survival than controls. Death rates from causes other than CRC among participants never became higher than among controls. CONCLUSION The lesser reduction in mortality from CRC of 11% compared to 18% after 5 screening rounds may be explained by the decrease in the number screened. Efficacy in those screened supports the introduction of countrywide screening in Denmark, but it must be ascertained that acceptability, proportion of early CRC and logistics all reach the same standard as in the randomized trial.
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Affiliation(s)
- O Kronborg
- Department of Surgery A, Odense University Hospital, Linde Alle 32, DK-5230 Odense, Denmark.
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Zheng S, Liu XY, Ding KF, Wang LB, Qiu PL, Ding XF, Shen YZ, Shen GF, Sun QR, Li WD, Dong Q, Zhang SZ. Reduction of the incidence and mortality of rectal cancer by polypectomy: a prospective cohort study in Haining County. World J Gastroenterol 2002; 8:488-92. [PMID: 12046076 PMCID: PMC4656427 DOI: 10.3748/wjg.v8.i3.488] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To reduce the incidence and mortality of rectal cancer and address the hypothesis that colorectal cancer often arise from precursor lesion (s), either adenomas or non-adenomatous polyps, by conducting a population-based mass screening for colorectal cancer in Haining County, Zhejiang, PRC.
METHODS: From 1977 to 1980, physicians screened the population of Haining County using 15 cm rigid endoscopy. Of over 240000 participants, 4076 of them were diagnosed with precursor lesions, either adenomas or non-adenomatous polyps, which were then removed surgically. All individuals with precursor lesions were followed up and reexamined by endoscopy every two to five years up to 1998.
RESULTS: After the initial screening, 953 metachronous adenomas and 417 non-adenomatous polyps were detected and removed from the members of this cohort. Further, 27 cases of colorectal cancer were detected and treated. Log-rank tests showed that the survival time among those cancer patients who underwent mass screening increased significantly compared to that of other colorectal cancer patients (P < 0.0001). According to the population-based cancer registry in Haining County, age-adjusted incidence and mortality of rectal cancer decreased by 41% and 29% from 1977-1981 to 1992-1996, respectively. Observed cumulative 20-year rectal cancer incidence was 31% lower than the expected in the screened group; the mortality due to rectal cancer was 18% lower than the expected in the screened group.
CONCLUSION: Mass screening for rectal cancer and precursor lesions with protocoscopy in the general population and periodical following-up with routine endoscopy for high-risk patients may decrease both the incidence and mortality of rectal cancer.
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Affiliation(s)
- Shu Zheng
- Cancer Institute, Zhejiang University, 88 Jiefang Road, HangZhou 310009, Zhejiang Province, China.
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Alberts DS. Reducing the risk of colorectal cancer by intervening in the process of carcinogenesis: a status report. Cancer J 2002; 8:208-21. [PMID: 12074318 DOI: 10.1097/00130404-200205000-00002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Risk factors for colorectal cancer have been identified, and significant advances have been made in understanding the process of colorectal carcinogenesis. The transition from normal colonic mucosa to adenomatous polyp to adenocarcinoma is a gradual process involving genetic and epigenetic instability that can take decades, offering numerous opportunities for early detection (e.g., colonoscopy screenings), lifestyle changes (e.g., reduced red meat intake, increased physical activity, and reduced alcohol/ tobacco exposure), and chemopreventive interventions. Aspirin and various other nonsteroidal anti-inflammatory drugs may have chemopreventive benefits for colorectal cancer and other human epithelial carcinomas, butthe long-term use of nonsteroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects. Recently, overexpression of cyclooxygenase-2 has been documented in colorectal tumors and numerous other pre-cancers and cancers. The development of selective cyclooxygenase-2 inhibitors, such as celecoxib, provides an opportunity for preventive intervention in the carcinogenic process. Celecoxib has been approved for the management of familial adenomatous polyposis and is under investigation for the management of sporadic colorectal polyps and for its potential as a chemopreventive agent for other cancers.
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Affiliation(s)
- David S Alberts
- Cancer Prevention and Control, Arizona Cancer Center, University of Arizona, Tucson 85724, USA
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Abstract
Screening for colorectal cancer has not obtained worldwide acceptance in spite of its proven survival benefit for average-risk persons and some high-risk groups. The incidence of and mortality from colorectal cancer are worrying in Europe as well as in the USA, Australia and Japan. The best evidence-based studies are those published on screening using faecal occult blood tests, endoscopic methods and different tumour markers having been evaluated to a lesser degree. Feasibility studies are necessary before massive screening can be undertaken because the results obtained from randomized studies may not be reproduced to a satisfactory degree in average- as well as high-risk populations. Primary prevention by dietary intervention and drugs has been studied in great detail, so far without any major breakthrough. This chapter will address different screening methods in populations with a varying risk of colorectal cancer, together with providing a short review of prevention and intervention strategies.
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Affiliation(s)
- O Kronborg
- Department A, Odense University Hospital, Odense C, DK-5000, Denmark
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Abstract
BACKGROUND Randomized controlled trials (RCTs) of lung cancer screening consistently show an excess number of cancer cases and longer survival in screened groups, but no difference in mortality between screened and control populations. METHODS The current study reviewed the various types of biases that confuse comparisons based on intermediate endpoints such as stage distribution and survival and the reasons for basing evaluations in RCTs of screening for early cancers on mortality from a specific cancer. RESULTS Four RCTs all showed improved stage of disease and survival in screened subjects, but there was no difference in mortality between screened and unscreened populations. The possible explanations for the higher incidence are chance (failed randomization) or "overdiagnosis" (detection of cases by screening that otherwise would never have surfaced). Analysis of the trial results confirmed that chance alone was a very unlikely explanation. Evidence suggests that some overdiagnosis of lung cancer is likely in screened subjects. This is a consistent observation in all other programs of screening for early cancers (breast, prostate, and neuroblastoma). CONCLUSIONS Overdiagnosis of cancer cases resulting from the screening process itself will give rise to excess cases of disease, and may, at least in part, explain the observations in the randomized trials.
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Affiliation(s)
- D M Parkin
- The International Agency for Research on Cancer, Lyon, France.
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