Colorectal cancer screening: A comparison of 35 initiatives in 17 countries

Authors


  • The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

  • International Colorectal Cancer Screening Network members: Principal Investigators, W.S. Atkin, J. Patnick; Expert working group, W.S. Atkin, J. Patnick, A. Miles, S.M. Moss, D. Weller, R. Ancelle-Park, N. Segnan, C. Senore, R.C. Klabunde, R.A. Smith, M. Nadel; Collaborators (in alphabetical order of department or institution), Cancer Care Ontario, Toronto, ON, Canada: T. Sullivan; Cancer Control Department, American Cancer Society, Atlanta, GA, USA: R.A. Smith; Cancer Office, General Direction of Health, Ministry of Health, Paris, France: M. Chedru, H. Creusvaux; Cancer Epidemiology Unit, University of Oxford, England, UK: V.S. Benson, J. Green, J. Watson; Cancer Research UK Health Behaviour Unit, Department of Epidemiology and Public Health, University College London, England, UK: A. Miles; Cancer Screening Technology Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan: H. Saito; Carmel Medicine Centre, Haifa, Israel: G. Rennert; Catalan Institute of Oncology, Barcelona, Spain: J. Espinas Pinol; Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA: M.R. Nadel; Centro di Prevenzione Oncologica, Rome, Italy: M. Crespi, D Lisi; Center for the Study of Cancer, Florence, Italy: M. Zappa; CPO Piemonte, Turin, Italy: N. Segnan, C. Senore; Department of Clinical Health Psychology, University College London, England, UK: A.K. Davies; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York: S.J. Winawer; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA: A.G. Zauber; Department of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong: J Sung, B. Wong; Division of Cancer Control and Population Sciences, National CancerSciences, National Cancer Institute, Bethesda, MD, USA: C. Klabunde; Division of Community Health Sciences, University of Edinburgh, Scotland, UK: D. Weller; Division of Gasteroenterology, Sunnybrook and Womens College Health, Toronto, ON, Canada: L. Rabeneck; Division of Gasteroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA: R. Schoen; Flinders Medical Centre, Adelaide, Australia: G. Young; Finnish Cancer Registry, Helsinki, Finland: N. Malila; Institut de Veille Sanitaire, Saint Maurice, France: R. Ancelle-Park, H. Goulard; Institut Jules Bordet, Brussels, Belgium: A. Grivegnée; Institute for Studies in Gastroenterology, Prague, Czech Republic: M. Zavoral; Institute of Cancer Research, London, England, UK: S.M. Moss; Institute of Oncology, Warsaw, Poland: E. Butruk, J. Regula; Institute of Preventative Medicine, National Taiwan University, Taipei, Taiwan: T, Hsiu-His Chen; Istito Oncologico Veneto, Padova, Italy: M. Vettorazzi, M. Zorzi; Servizio di Gastroenterologia, Verona, Italy: A. Ederle, A. Fantin; Kaiser Permanente, Oakland, CA, USA: T.R. Levin; Kirurgisk Afdeling A, Odense Universitets Hospital, Odense K, Denmark: O. Kronborg; National Cancer Control Initiative, Carlton, Victoria, Australia: J. St. John; NHS Cancer Screening Programmes, Sheffield, England: J. Patnick; Population Screening Section, Australian Government Department of Health and Aging, Canberra, Australia: A. Koukari, M. Otuszewski; Veteran Affairs Medical Center, Portland, OR, USA: D. Lieberman; Quästor der GMS, Kantonsspitla Uri, Switzerland: U. Marbet; Registre des Cancers, Dijon, France: J. Faivre; Shin Kong Wu Hol Su Memorial Hospital, Taipei, Taiwan: K. Yang; The Cancer Registry of Norway, Montebello, Norway: G. Hoff; The Scarborough Hospital, Scarborough, ON, Canada: T.F. Shapero; UK Colorectal Cancer Unit, St Mark's Hospital, NW London Hospitals Trust, Harrow, Middlesex, England, UK: W.S. Atkin; University of Western Australia, Western Australia, Australia: J. Olynyk

Abstract

Although in its infancy, organized screening for colorectal cancer (CRC) in the general population is increasing at regional and national levels. Documenting and describing these initiatives is critical to identifying, sharing and promoting best practice in the delivery of CRC screening. Subsequently, the International Colorectal Cancer Screening Network (ICRCSN) was established in 2003 to promote best practice in the delivery of organized screening programs. The initial aim was to identify and document organized screening initiatives that commenced before May 2004. Each identified initiative was sent 1 questionnaire per screening modality: fecal occult blood test, flexible sigmoidoscopy or total colonoscopy. Information was collected on screening methodology, testing details and initiative status. In total, 35 organized initiatives were identified in 17 countries, including 10 routine population-based screening programs, 9 pilots and 16 research projects. Fecal occult blood tests were the most frequently used screening modality, and total colonoscopy was seldom used as a primary screening test. The eligible age for screening ranged from 40 years old to no upper limit; most initiatives included participants aged 50 to 64. Recruitment was usually done by a mailed invitation or during a visit to a family physician. In conclusion, this is the first investigation describing the delivery of CRC screening protocols to various populations. The work of the ICRCSN is enabling valuable information to be shared and a common nomenclature to be established. © 2007 Wiley-Liss, Inc.

Worldwide each year, more than 940,000 new cases of colorectal cancer (CRC) are diagnosed and nearly 500,000 people die from the disease.1 CRC is the third most common cancer in both men and women worldwide, and the second most common cancer in the industrialized world.2

Early detection of CRC has been shown to improve outcomes through the detection of early-stage cancers and precursor lesions.3 Because early-stage disease frequently is asymptomatic, screening of the general population could decrease CRC incidence and mortality. There are 3 frequently used screening modalities: fecal occult blood test (FOBt), which reveals traces of blood in stool samples (an early sign of CRC); flexible sigmoidoscopy (FS), which involves visual inspection of the distal bowel for polyps and cancers; and total colonoscopy (TC), which visualizes the entire bowel and therefore is a more invasive examination.

Biennial screening using a guaiac FOBt (gFOBt) was found to decrease mortality by ∼15% after 13 years of follow-up in a large randomized trial in Funen, Denmark,4, 5 and by 13% after an 11-year follow-up in Nottingham, United Kingdom.6, 7 Neither study found a decrease in incidence, although follow-up continues. A more complex trial in Minnesota, USA, compared annual and biennial screening using FOBt.8 After an 18-year follow-up, mortality decreased by 33% in participants screened annually, and 21% in those screened biennially.9 Reductions in incidence of 20% and 17% were also observed for annually and biennially screened individuals, respectively.10

Four large-scale randomized clinical trials are evaluating FS as a screening tool. Baseline findings have been published showing that FS screening is safe (no major complications and relatively few perforations) and acceptable to the population.11–15 A randomized clinical trial of FS screening in Telemark, Norway reported an 80% reduction in CRC incidence rates with a 13-year follow-up. The numbers in this study were small, however.16

Although TC detects adenomas beyond the reach of FS no randomized clinical trials have been conducted. However, the U.S. National Polyp Study reported a reduction in the incidence of CRC when comparing those who had a complete colonoscopy where all adenomas were removed, to 3 reference groups: patients with polyps ≥1 cm who declined to undergo surgery; patients who had all rectal adenomas removed; and the final cohort was a sample of the general population.17

A country's screening initiatives need to be adapted to suit its population size, health care system and methods of funding. However, it will be beneficial to collect and share implementation and performance data among countries. Information on the effectiveness of technologies and methodologies can benefit existing programs. It can also provide insights and guidance to those in the planning stages of screening initiatives. Additionally, comparing the effectiveness of different screening modalities within a country could inform decision-making about an appropriate national screening protocol specific to the needs of that country. To facilitate the sharing of such information and comparisons, it is important to have a common nomenclature and for initiatives to be collecting the appropriate data. However, because colorectal screening is in its infancy in most countries, a common language to describe the screening process and common measures by which quality can be examined for all tests and types of programs have yet to be established.

In June 2002, the International Union Against Cancer and the American Cancer Society sponsored an international workshop in Oslo, Norway, on facilitating screening for CRC.18 From this meeting it was clear that a great deal of CRC screening activity was taking place worldwide, and that it would be beneficial to describe the activity and build a network to share experience and knowledge. Subsequently, the Centers for Disease Control and Prevention and the American Cancer Society supported a collaborative effort with Cancer Research UK to develop the International Colorectal Cancer Screening Network (ICRCSN).

The first aim of the ICRCSN was to identify and document the status of organized screening initiatives, and that information is reported in the present article. As a next step, the ICRCSN is focused on establishing a consensus minimum set of screening program descriptors and quality assurance measures with common definitions and measurement metrics to enable program evaluation and comparisons.

Abbreviations:

CoCaP, Colon Cancer Prevention Program; CRC, colorectal cancer; FIT, fecal immunochemical test; FOBt, fecal occult blood test; FS, flexible sigmoidoscopy; gFOBt, guaiac fecal occult blood test; ICRCSN, International Colorectal Cancer Screening Network; PLCO, Prostate, Lung, Colon and Ovarian; TC, total colonoscopy; VA, Veterans Affairs.

Methods

Known colorectal screening initiatives in progress (either screening or in follow-up after screening) as of May 2004 were contacted to assess their interest and potential for involvement in the ICRCSN. Initial approaches were made through personal knowledge of grant holders, conference contacts and literature and internet searches. Each contact was asked to identify other initiatives. The lead of each initiative was identified and a working group, composed of 11 members from 5 countries, was convened to develop the methodology and principles for the survey.

To be included in the Network, screening initiatives were required to meet a set of criteria. Initiatives were required to be carrying out screening of the general population, targeting asymptomatic people within a defined age range, and in an organized manner, as defined by the International Agency for Research on Cancer (IARC).19 Characteristics of an organized screening program include an explicit policy with specified age categories, method and interval for screening; a defined target population; a management team responsible for implementation; a health care team for decisions and care; a quality assurance structure; and a method for identifying cancer occurrence in the target population. Initiatives were further classified as (i) programs in which screening is offered as part of routine health care; (ii) pilot studies carried out in a limited population for a limited time to assess feasibility, with a view to possibly extending to a program, or (iii) research projects with a fixed sample size and duration aimed at answering a specific question. If an initiative used more than 1 screening modality, then each modality (or combination of modalities offered to the same participant) was considered a separate activity.

Between November 2003 and March 2004, 2 questionnaires were designed to elicit information about screening initiatives in the countries and regions represented by members of the ICRCSN. The questionnaires were patterned after instrumentation developed by the International Breast Cancer Screening Network to characterize breast cancer screening activities among participating countries (http://appliedresearch.cancer.gov/ICSN/). The first questionnaire, the National Questionnaire, asked about a country's policies and guidelines on CRC screening, as well as for specific information about screening initiatives. The questionnaire included details of modality, target population and some information about protocol.

In addition to the National Questionnaire, modality-specific questionnaires were designed for FOBt, FS and TC. The questionnaires contained 6 sections: contact details for activity leads and other individuals involved in the activity, screening methodology, testing details, status of the initiative/activity, screening performance and outcomes and quality assurance.

Drafts were reviewed by a subgroup of the working group and pilot tested with a sample of initiative representatives of the ICRCSN. The finalized questionnaires were distributed in March 2004 via email to representatives from all known initiatives.

An international workshop for survey respondents was held in London in May 2004. Results of the survey were described and discussed. Areas requiring classification or confirmation were identified and refinements made. Unclear responses to the questionnaire were clarified by subsequent communications with the initiative leads.

Results

A total of 35 organized independent initiatives delivering CRC screening to asymptomatic populations were identified. These were then analyzed by geographic location, screening modality and type of initiative.

Geographical variation

The 35 organized initiatives were identified in 17 countries in 3 geographic regions (as defined by the World Health Organization, or by proximity where necessary): Europe (n = 23), the Americas (n = 6) and the Western Pacific (n = 6) (Table I). Initiatives were funded primarily by public funds, usually from central and local governments. Forty-six percent of the initiatives were funded only by government funds, and 31% were funded by the government and at least one other source. Initiatives were funded to a lesser extent by charities, health insurance and self-funding. A very small contribution came from industry or other private sources.

Table I. A Description of Each Initiative, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004
CountryInitiative typeModalityName of initiativeRegion(s)Target populationAge rangeTarget population in age rangeFunding sourceYear activity beganTotal screening episodes before May 2004
  • CG, central government; FOBt, fecal occult blood test; FP, family practitioner; FS, flexible sigmoidoscopy; HI, health insurance; HMO, Health Maintenance Organization; LG, local government; O, other; PC, private/charity; S, self-funded; TC, total colonoscopy.

  • 1

    The number of screening episodes at the end of 2004.

  • 2

    Size of trial population.

  • 3

    Not a country defined in the WHO regions, but is located in the Western Pacific.

EUROPE
BelgiumResearchFSScreening for CRC Using SigmoidoscopyAllHMO members50–7510,000S19931,912
Czech RepublicProgramFOBtNational Program of Screening for CRCAllPopulation visiting FP50+3,700,000CG, HI20011,000,000
DenmarkResearchFOBtRandomized Study of Screening for CRC with FOBtFunenResident population45–75140,000PC, CG1985128,703
FranceResearchFOBtBurgundy StudyBurgundy, Saône-et-LoireResident population45–74155,000CG, HI198845,642
PilotFOBtNational Program for CRC22 DépartementsResident population50–744,500,000CG, HI2003716,5221
 IsraelProgramFOBtCHS National CRC Screening ProgramAllHMO members50–74700,000HMO199360,000
 ItalyResearchFSSCOREArezzo, Biella, Genova, Milan, Rimini, TurinVolunteers55–64256,000PC19959,999
PilotFOBtSCORE 2Biella, Florence, Milan, Rimini, TurinResident population55–64122,000LG, PC19995,120
FS9,525
ProgramFOBtNHS Funded Regional Screening ProgramTuscanyResidential population of 7 local health units50–70969,000LG2000259,227
ProgramFOBtNHS Funded Regional Screening ProgramVenetoResident population of 4 local health units50–69173,000LG200242,800
ResearchFOBtAccademia Multidisciplinare Oncologia Digestiva (AMOD)65 FP centers within 9 regionsFP patients55–649,8992PC2002732
TC236
ProgramFSUn'occhiata ti salva la vitaVenetoResidential population of 1 local health unit605,000LG20031,600
ResearchFOBtSCORE 3Biella, Florence. Milan, Rimini, Turin, VeronaResident population55–64122,000LG, PC20031,965
FS1,944
TC1,597
ProgramFOBtNHS Funded Regional Screening Program (Prevenzione Serena)Turin, NovaraResident population5817,900LG20035,333
FS TurinResident population59–69125,00020043,284
 NorwayResearchFS onlyNORCCAP-1Oslo, TelemarkResident population50–64100,000CG, PC19996,695
FS + FOBt6,266
 PolandProgramTCColonoscopic CRC ScreeningAllFP patients50–656,500,000CG200030,360
 SpainPilotFOBtCatalan CRC Pilot Screening ProgrammeCatalonia, l'HospitaletResident population50–6969,000LG200010,962
ResearchFOBtSigmoidoscopy Screening Research ProjectCatalonia, Vilafranca del PenedèsResident population50–694,726LG2004322
FS    2,023  1,084
 SwitzerlandResearchFOBtGlarus, Vallée du Joux, UriResident population50–8020,000O2000297
FS       112
TC       2,044
FS + FOBt       278
United KingdomResearchFOBtThe Nottingham CRC Screening TrialNottingham, EnglandFP patients45–74153,0002CG1981134,128
ResearchFSUK FS Screening Trial14 areas in England, Scotland and WalesFP patients55–64376,000CG, PC199640,674
PilotFOBtThe UK Pilot of CRC ScreeningEngland (3 areas) and NE Scotland (2 areas)Resident population50–69476,000CG2000260,000
ResearchFSNurses Led FS Screening StudyHarrow, North LondonFP patients60–64500PC2003150
 THE AMERICAS
 CanadaProgramFSColon Cancer Detection ClinicOntarioFP patients50+500,000HI19991,865
PilotFOBtOntario FOBT Pilot StudyOntario6 regions of FP patients, public health units50–75440,000LG2004Not known
 United States of AmericaResearchFSPLCO Cancer Screening Trial10 states10 Clinical Centers55–74154,000CG199364,700
ProgramFSCoCaP (Kaiser Permanente)Northern CaliforniaHMO members50+500,000CG, HMO, O1994350,000
PilotFOBtFOBt in Veterans AffairsAllVeterans Affairs patients50+30,000CG2000Not known
ResearchTCNational Colonoscopy Study (Phase I)3 statesHMO members, wellness clinic, resident population50–64975,000CG2000622
 WESTERN PACIFIC
 AustraliaPilotFSFS for CRC in Average-Risk SubjectsFremantle, WAResident suburban population55–6480,000LG19953,500
ResearchFOBtRelative performance and acceptability of FOBt typesAdelaide, SASouthern residential population50+100,000CG, PC, O19974,165
PilotFOBtThe Australian Bowel Cancer Screening PilotMelbourne, Vic; Adelaide SA; MacKay, QldResident population55–7457,000LG, CG200225,840
 Hong KongResearchTCScreening for CRC in ChineseAllResident population50–70480,000PC2000510
 JapanProgramFOBtNational CRC Screening ProgramAllNational health insurance holders40+35,000,000CG, S1992∼6.4 million
 Taiwan3PilotFOBtKeelung Community- based Integrated ScreeningKelung, Northern TaiwanResident population50–7981,000LG199922,716

Modality analysis

We gathered information on 3 screening modalities: FOBt (Table IIa), FS (Table IIb) and TC (Table IIc). Seven initiatives used more than 1 modality or combination of modalities. Due to different protocols, each activity was described separately, which resulted in 45 activities overall.

Table IIa. A Description of Each Activity, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004. FOBt Protocol
Country, region (initiative)Type of initiativeType of testBrand name of testScreening intervalNumber of bowel movements sampledTotal samplesRoutine dietary restriction
  • G, guaiac; I, immunochemical.

  • 1

    In combination with flexible sigmoidoscopy.

  • 2

    Not a country defined in the WHO regions, but is located in the Western Pacific.

EUROPE
Czech Republic (National study)ProgramGHemoccultBiennial33Yes
Denmark, FunenResearchGHemoccult IIBiennial36Yes
France (National pilot)PilotGHemoccultBiennial36No
France, BurgundyResearchGHemoccultBiennial36No
Israel (National study)ProgramGHemoccult SENSAAnnual36Yes
Italy (SCORE 2)PilotIRPHA immudiaBiennial11No
Italy, TuscanyProgramIAlpha WassermanBiennial11No
Italy (AMOD)ResearchGHemoccult SENSA IIAnnual36Yes
Italy, VenetoProgramIAlpha Wasserman, SentinelBiennial11No
Italy (SCORE 3)ResearchIRPHA immudiaBiennial11No
Italy (Prevenzione Serena)ProgramIAlpha WassermanBiennial11No
Norway (NORCCAP-1)1ResearchIFlexSure OBTOnce33No
Spain, CataloniaPilotGHema ScreenBiennial36No
Spain, CataloniaResearchGHema ScreenBiennial36No
SwitzerlandResearchGHemoccultAnnual33No
Switzerland1ResearchGHemoccultAnnual33No
United Kingdom, NottinghamResearchGHemoccultBiennial36Yes
United Kingdom, England and ScotlandPilotGHema ScreenBiennial36No
THE AMERICAS
Canada, OntarioPilotGHemoccult IIOnce36No
United States of America (Veterans Affairs)PilotGHemoccult IIAnnual33No
WESTERN PACIFIC
Australia, AdelaideResearchG, IHemoccult, InSureAnnual33Yes
Inform22No
 Australia (Pilot)PilotIMagstream HemS, InformBiennial22No
 JapanProgramINot specifiedAnnual22No
 Taiwan2PilotIEikenAnnual11No
Table IIb. A Description of Each Activity, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004. Flexible Sigmoidoscopy Protocol
Country, region (initiative)Type of initiativeScreening intervalDiscipline of endoscopistWhere is screening conducted?Bowel preparationBowel preparation locationCriteria for polyp removal at sigmoidoscopyCriteria for colonoscopy
  • G, gastroenterologist; M, medics: consultants and specially trained junior doctors; N, nurse; P, program; PCP, primary care practitioner; PS, pilot study; RP, research project; S, surgeon.

  • 1

    In combination with fecal occult blood tests.

EUROPE
BelgiumResearchEvery 5 yearsGHospitalEnemaHomeNone removed5+ adenomas, adenomas ≥ 10 mm, adenomas with >25% villous structure, high-grade dysplasia
Italy (SCORE)ResearchOnceGHospitalEnemaHomePolyps ≤5 mmPolyps >5 mm, high risk small polyps
Italy (SCORE 2)PilotOnceG, SHospitalEnemaHomePolyps <10 mm3 adenomas <10 mm, polyps ≥10 mm, CRC, polyps with severe dysplasia or villous component <20%
Italy, VenetoProgramOnceGHospitalEnemaHomePolyps <6 mm3 adenomas <10 mm, polyps ≥10 mm, CRC, polyps with severe dysplasia or villous component <20%
Italy (Prevenzione Serena)ProgramOnceG, SHospitalEnemaHomePolyps <10 mm3 adenomas <10 mm, polyps ≥10 mm, CRC, polyps with severe dysplasia or villous component <20%
Italy (SCORE 3)ResearchOnceG, SHospitalEnemaHomePolyps <10 mm3 adenomas <10 mm, polyps ≥10 mm, CRC, polyps with severe dysplasia or villous component <20%
Norway1ResearchOnceMHospitalEnemaUnitNone removedPolyp >10 mm and any adenoma
SpainResearchOnceGHospitalEnemaHomePolyps <10 mm3+ adenomas, polyps 10 mm, tubulovillous or villous histology, or severe dysplastic or neoplastic polyp
SwitzerlandResearchEvery 5 yearsGHospital, officeEnemaUnitNone removedAny polyp
Switzerland1ResearchEvery 5 yearsGHospital, officeEnemaUnitNone removedAny polyp
United Kingdom (Nurse-led Study)ResearchOnceNHospitalEnemaHomePolyps <10 mm3+ adenomas, polyps >10 mm
United Kingdom (Flexisig trial)ResearchOnceG, SHospitalEnemaHomePolyps <10 mm3+ adenomas, 20+ hyperplastic polyps above the distal rectum, polyps ≥10 mm, tubulovillous or villous histology, severe dysplasia
THE AMERICAS
Canada, OntarioProgramEvery 5 yearsNHospitalEnemaHomeNone removedAny polyp
United States of America (PLCO)ResearchEvery 5 yearsG, NHospital, officeEnemaHomeNone removedAs per FP
United States of America (CoCaP)ProgramEvery 10 yearsG, PCP, NHospitalEnema, laxativeHomePolyps <5 mm2+ tubulovillous adenomas (1 if family history), polyps >10 mm, with villous histology or high grade dysplasia
WESTERN PACIFIC
Australia, FremantlePilotEvery 5 yearsG, SHospitalEnemaUnitNone removedAdenomas, multiple hyperplastic polyps
Table IIc. A Description of Each Activity, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004. Total Colonoscopy Protocol
Country, region (initiative)Type of initiativeScreening intervalDiscipline of endoscopistWhere is screening conducted?
  • G, gastroenterologist; S, surgeon.

  • 1

    Office of the endoscopist.

EUROPE
Italy (AMOD)ResearchOnceGHospital
Italy (SCORE 3)ResearchOnceGHospital
PolandProgramEvery 10 yearsG, SHospital
SwitzerlandResearchEvery 10 yearsGHospital, office1
THE AMERICAS
United States of America (National Study)ResearchOnceGOutpatient endoscopy unit
WESTERN PACIFIC
Hong KongResearchEvery 5 yearsGHospital

Of the 45 activities, 22 were using FOBt only. In addition, 2 research projects, 1 in Norway and 1 in Switzerland, used FOBt in combination with FS. Fourteen were using a gFOBt only, 9 used a fecal immunochemical test (FIT) only and 1, an Australian research project, used both types. Fourteen of the FOBt activities used biennial screening, 8 screened annually, and 2 screened once only during the study period.

The age groups of the target populations varied widely. Although all FOBt activities included adults aged 59–64 years, some enrolled participants in their 40s. Some activities had no upper age limit, while others ended recruitment between ages 64 and 80. Dietary restriction was common for those using gFOBt, with counseling to remove vitamin C, red meats and nonsteroidal anti-inflammatory drugs from the diet prior to stool samples being taken. Every activity used colonoscopy for investigation after a positive FOBt result. The definition of a positive test varied. For example, some activities recorded a participant as positive if 1 or more test squares were positive on the FOBt card (pilot studies in particular). Other activities deemed a participant as positive if 5 or more squares on multiple cards were positive.

Fourteen of the initiatives were using FS only as their screening modality. In addition, 1 initiative in Norway and 1 in Switzerland used FS in combination with FOBt. Nine of these 16 activities were “once only” screening, although whether this was offered at a particular age (58 or 60 years old) or to an age range (50–64 years old) varied. Six of the activities offered screening every 5 years; one, the Colon Cancer Prevention Program (CoCaP) in Northern California, offered screening every 10 years. Many of the activities used a home-based enema administered by the patient as their bowel preparation, whereas Australia, Norway and Switzerland routinely used enemas in the screening unit. The CoCaP also used laxatives as part of its bowel preparation.

Nurses performed endoscopy in a program in Ontario, Canada and a research study in the United Kingdom. Nurses, gastroenterologists or primary care practitioners performed endoscopy in the U.S. Prostate, Lung, Colon and Ovarian (PLCO) cancer screening trial and the CoCaP program. Elsewhere, gastroenterologists and (to a lesser extent) surgeons performed the procedure.

Most activities had clear protocols for polyp removal and criteria for referral for a colonoscopy. In Australia (the pilot study), Belgium, Canada, Norway, Switzerland and the U.S. PLCO trial, polyps were not removed during FS and patients were referred for colonoscopy.

Six activities used colonoscopy as a screening technique; 3 on a once-only basis, 1 at 5-year intervals, and 2 at 10-year intervals. All colonoscopy activities offered screening to participants aged 55–64; however, the age at screening ranged from 50 to 80, depending on the activity. Colonoscopies were routinely conducted in the hospital, except in the Swiss research project (in which they also were carried out in a doctor's office) and in the U.S. National Colonoscopy Study (in which colonoscopies were performed in an outpatient endoscopy unit). In all studies, gastroenterologists performed the screening colonoscopy. In Poland, surgeons were also able to perform colonoscopy.

Initiative designs

Ten routine population screening programs were identified in 7 countries. Eight countries (9 initiatives) were running pilot studies, and research projects continued in 11 countries (16 initiatives). Italy was running a number of different local programs, rather than a single national program. Research projects coexisted in countries that were operating pilot projects or full programs.

Programs

Five of the identified programs offered FOBt only, 3 offered FS only, 1 offered TC only and 1 program in Italy (Prevenzione Serena) offered both FOBt and FS (Table IIIa). The most established programs were in Japan and Israel, as well as CoCaP in the United States. These programs began recruitment in 1992, 1993 and 1994, respectively. A variety of recruitment methods were used; a mailed invitation, usually personalized, was the most popular method where population registers were available. Other methods included referral by a family practitioner and the use of media. Practice varied as to whether the written results were sent to the patient, the patient's usual family physician, or both. All programs had mechanisms to follow up all positive FOBt or FS results, except for the Czech Republic and the CoCaP program. All programs had evaluation systems in place.

Table IIIa. Initiative Designs, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004
Country, region (initiative)ModalityInvitations and remindersStructured system for evaluationWritten confirmation of normal and abnormal resultsMechanism to follow up positive test
System1Population register2MethodAre reminders sent?
  • ER, electoral roll; FOBt, fecal occult blood test; FP, family physician; FPR, family physician registry; FS, flexible sigmoidoscopy; HMO, Health Maintenance Organization; IR, insurance registry; LHA, local health authority; N/A, not applicable; PR, population registry (e.g. national registry); PSR, pap smear registry; SCR, screening clinic registry; TC, total colonoscopy; VAR, veteran affairs register.

  • 1

    Is a structured information system used to manage invitations and reminders?

  • 2

    A register that contains a list of possible participants, such as a population census.

  • 3

    Not a country defined in the WHO regions, but is located in the Western Pacific.

  • 4

    Doctor received only normal results.

  • 5

    Doctor received only abnormal results.

PROGRAMS
 EUROPE
Czech RepublicFOBtNoNoneOpportunistic: When visit FP, public campaignNoYesDoctorNo
IsraelFOBtYesHMOMailed invite and post card to order test kitNoYesDoctorYes
Italy, TuscanyFOBtYesFPR, PRMailed personal invite and leaflet from FP, mediaYesYesPatientYes
Italy, VenetoFOBtYesFPR, PRMailed personal invite and leaflet from FP, mediaYesYesDoctor, PatientYes
Italy, VenetoFSYesFPR, PRMailed personal invite, leaflet and appointment date from FP, age dependent self-referral, mediaYesYesDoctor, PatientYes
Italy (Prevenzione Serena)FSYesFPR, PRMailed personal invite, leaflet and prefixed appointment from FP, age dependent self-referral, mediaYesYesDoctor, PatientYes
FOBtMailed personal invite and leaflet from FP, media
 PolandTCNoNoneOpportunistic: When visit FP, mediaNoYesPatientN/A
 THE AMERICAS
 CanadaFSNoNoneOpportunistic: when visit FPNoYesDoctorYes
 United States of America (CoCaP)FSNoNoneOpportunistic: when visit FPNoYesDoctor, PatientNo
 WESTERN PACIFIC
 JapanFOBtYesPR, IROpportunistic: news letter issued by local governmentNoYesPatientYes
 PILOT STUDIES
  EUROPE
 FranceFOBtYesIRFP if visit FP, mailed invite otherwiseYesYesDoctor, PatientYes
 Italy (SCORE 2)FOBtYesFPR, PRMailed personal invite from FP, leaflet and test kit mailed to 1st arm in 1st roundYesYesDoctor, PatientYes
FSMailed personal invite from FP, leaflet, and prefixed appointment
 SpainFOBtYesFPRMailed invite and leafletYesYesDoctor, PatientYes
 United Kingdom, England  and ScotlandFOBtYesLHAMailed invite, then test kit, mediaYesYesDoctor, PatientYes
 THE AMERICAS
 CanadaFOBtYesFPROpportunistic: face-to-face, mediaNoYesDoctorNo
 United States of America (VA)FOBtYesVARFP receive annual computer prompt when patient is visitingNoYesDoctor, PatientNo
 WESTERN PACIFIC
 Australia, FremantleFSYesERMailed inviteYesYesDoctor, PatientYes
 Australia (Pilot)FOBtYesIRMailed invite, booklet, questionnaire, consent form and test kitYesYesDoctor, PatientYes
 Taiwan3FOBtYesPR, PSRTelephone inviteNoYesPatientNo
RESEARCH PROJECTS
 EUROPE
BelgiumFSYesSCROpportunistic: when visit FPYesYesDoctor, PatientYes
Denmark, FunenFOBtYesPRMailed invite and test kitYesYesDoctor, Patient4Yes
France, BurgundyFOBtYesIRMailed invite and leafletYesYesDoctor, PatientYes
Italy (SCORE)FSYesFPRMailed personal invite and prefixed appointment from FPYesYesDoctor, PatientYes
Italy (AMOD)FOBtYesFPRPersonal mailed invite from FPYes (telephone)YesDoctor, PatientNo
TCN/A
 Italy (SCORE 3)FOBtYesFPR, PRPersonal mailed invite from FP, media in 1 regionYesYesDoctor, PatientYes
FSPersonal mailed invite and prefixed appointment from FP, media in 1 regionYes
TCPersonal mailed invite and prefixed appointment from FP, media in 1 regionN/A
 NorwayFS onlyYesPRMailed invite and appointment dateYesYesPatientYes
FS + FOBtMailed invite, test, and appointment date
 SpainFS, FOBtYesFPRMailed invite and leafletYesYesDoctor, PatientYes
 SwitzerlandFOBtYesPRMailed invite, public lectures, mediaYesYesPatientYes
FSYesYes
TCNoN/A
FS + FOBtYesYes
 Nottingham,  United KingdomFOBtYesFPRPersonal mailed test kit and invite from FPNoYesDoctor, PatientYes
 United Kingdom  (Flexisig)FSYesFPRMailed invite with prefixed appointmentYesYesDoctor, PatientYes
 United Kingdom (Nurse-led study)FSYesFPRMailed leaflet, followed by mailed invite, appointment given, enema postedYesYesDoctor, PatientYes
 THE AMERICAS
 United States of America (PLCO)FSYesERMailed invite and leaflet, mediaYesYesDoctor, PatientYes
 United States of America (National TC Study)TCYesHMO, PR, SCRMailed invite, telephone, face-to-faceYesYesDoctor, PatientN/A
 WESTERN PACIFIC
 Australia, AdelaideFOBtYesERMailed invite and test kitYesYesDoctor, Patient5Yes
 Hong KongTCNoNoneHealth Exhibition, volunteerNoNoDoctor, PatientN/A

Pilot studies

Seven of the identified pilot projects offered FOBt, 1 offered FS and 1 in Italy (SCORE 2) offered both (Table IIIa). All 9 projects had some form of population register available, and systems in place for invitations and reminders (except for Canada, the U.S. Veterans Affairs (VA) pilot study and Taiwan). All studies had structured systems in place for evaluations, and 7 sent the results to both the patient and their usual doctor. The exceptions were Canada (only the patient's doctor received the results) and Taiwan (only the patient received the results). Canada, the U.S. VA pilot study and Taiwan had no mechanisms to follow up a positive test.

Research projects

Four of the identified research projects offered FOBt only, 5 offered FS only, 2 offered TC only and 5 offered a combination of 2 or 3 modalities (Table IIIa). Half of the population in the Norwegian study received FOBt screening in combination with FS. All except Hong Kong used some form of population register for recruitment. In addition, the majority of the initiatives had systems in place for evaluation, as well as routinely sending reminders to nonresponders. All projects reported normal and abnormal results to the patients. Eleven also reported normal results to physicians; 13 reported abnormal results to physicians.

Most of the projects were randomized controlled trials. Switzerland and Hong Kong described their studies as cohort studies; Belgium and the nurse-led study in the United Kingdom were described as feasibility studies (Table IIIb). It was in these initiatives that the greatest mix of protocols was found, with various combinations of modalities being used.

Table IIIb. Research Project Status, Presented Alphabetically by Country Within Regions Defined by the World Health Organization Where Possible, 2004
Country, region (initiative)ModalityNature of initiativeRecruitment complete prior to May 2004Evaluation complete prior to May 2004Research question
  1. C, cohort; F, feasibility study; FOBt, fecal occult blood test; FS, flexible sigmoidoscopy; RCT, randomized clinical trial; TC, total colonoscopy.

EUROPE
BelgiumFSFNoNoIs left colonoscopy a good screening tool in a population attending general cancer screening visits?
Denmark, FunenFOBtRCTYesYesDoes Biennial screening by FOBt reduce mortality from CRC?
Burgundy, FranceFOBtRCTYesYesTo assess acceptability and efficiency of FOBt screening in reduction of mortality from CRC
Italy (SCORE)FSRCTYesNoTo assess the FS screened individuals to controls of usual care
Italy (AMOD)FOBt, TCRCTNoNoTo assess the rate of compliance to and relative efficacy of FOBt and TC in screening for CRC
Italy (SCORE 3)FOBt, FS, TCRCTNoNoComparisons of attendance, detection rates and acceptability of TC, FS and FOBt as primary screening tests for CRC
NorwayFOBt + FSRCTYesNoComparison of effectiveness of once-only FS or FOBt and FS combined in detection of CR Neoplasm
SpainFOBt, FSRCTYesYesComparisons of acceptability of FS and FOBt
SwitzerlandFOBt, FS, TC, FS + FOBtCYesNoInvestigating preference, acceptance, compliance and quality of screening in a population based set-up
United Kingdom, NottinghamFOBtRCTYesNoDoes Biennial FOB screening reduce mortality from CRC?
United Kingdom (Flexisig)FSRCTYesYesIs FS screening effective in reducing CRC incidence and mortality?
United Kingdom (Nurse-led study)FSFNoNoTo examine the feasibility and acceptability of a nurse-led screening FS service
THE AMERICAS
United States of America (PLCO)FSRCTYesOngoingIs FS screening effective in reducing CRC mortality?
United States of America (National TC Study)TCRCTYesNoWhat is the feasibility of screening TC in a mixed gender, geographically representative population as measured by resource utilization, acceptance, outcome and facilitation of access to screening?
WESTERN PACIFIC
Australia, AdelaideFOBtRCTNoNoComparison of Guaiac and FIT for screening for CRC, looking mainly at relative performance of different FOBt and behavioural issues
Hong KongTCCYesYesAssess the accuracy and safety of FOBt and FS, and compared against TC for screening of CR neoplasms in average-risk Chinese subjects older than 50 years

Discussion

The publication during the early and mid 1990s of trial and study results demonstrating the efficacy of screening for CRC had led, by the early years of the 21st century, to the implementation of a number of diverse screening initiatives in several countries of the world, in particular those with a high incidence of CRC. This is the first investigation describing the delivery of screening protocols to various populations.

Of the 17 countries identified by the ICRCSN that had begun organized CRC screening prior to May 2004, only 4 provided national programs. Three of these programs offered FOBt (Czech Republic, Israel and Japan) as their screening modality; one, Poland, offered TC. Six other programs (4 in Italy) were offered only at a regional level. In addition, there were 4 central government-funded pilot studies reported (France, United Kingdom, United States and Australia), most of which have subsequently progressed into national programs [France, United Kingdom (http://www.cancerscreening.nhs.uk/bowel/index.html) and the U.S. VA program]. Several of the other pilot studies had local government funding and may advance to regional programs in the future.

Fecal occult blood testing was the most frequently used screening modality, possibly because of the encouraging results in terms of acceptability, feasibility and efficacy from previous randomized clinical trials.4, 6, 8 In 1999, FOBt was accepted by the European Union as the standard for CRC screening.20 Several initiatives have used protocols based on those from the randomized clinical trials (for example, timing of screening, use of gFOBt, taking 2 samples from 3 consecutive bowel movements and dietary restriction). Some more recent FOBt initiatives have used FIT rather than gFOBt.

FS also was frequently used. Although large clinical trials of FS screening do exist (none are completed), they are more recent than those using FOBt, and there are fewer, if any, initiatives following trial protocols.11, 12, 14, 15 Bowel preparation for FS screening was fairly uniform, in that every participant had an enema that was typically self-administered at home. Screening typically occurred only once, but 5-year and 10-year intervals also were used. Referral for colonoscopy varied from any polyp being identified to criteria based on the number, size and histopathology of polyps found through FS.

TC was used in only 6 initiatives (1 program and 5 research projects), even though it is considered the “gold standard” for CRC identification. Gastroenterologists always performed TC, except in Poland where surgeons also performed the procedure. Colonoscopies were conducted in a hospital for all initiatives, as well as in the office of the gastroenterologist in Switzerland and in an outpatient endoscopy unit in the United States. Once-only screening was most common, however, 5-year screening was conducted in Hong Kong, and 10-year screening in Poland and Switzerland.

At this stage there appears to be no preferred method of conducting CRC screening, defining a positive screening test for purposes of initiating follow-up, and for follow-up itself. Information was collected in the survey on screening performance and outcomes and quality assurance measures; however, because of the lack of standardized definitions, more information is required on these topics before conclusions can be drawn. Consequently, continued activity for the ICRCSN will concentrate on the development of quality assurance protocols and indicators to allow commonly understandable results to be reported across all participants in the Network.

Unfortunately, not all organized CRC screening initiatives in existence in 2003/2004 were included in this report. Some initiatives were not brought to the attention of the ICRCSN until after data collection. We will continue to include initiatives as they are identified.

In conclusion, the knowledge gained from programs, research projects and pilot studies can be shared and used in the advancement of CRC screening. The establishment of the ICRCSN has made the sharing of valuable information possible and has created a connection among initiatives across the world. It is the intention that preferred protocols will be established in the future, establishing uniform screening methodologies and guidelines that can be followed by future initiatives. The continued support of the Network's members will help both new and existing initiatives reach their full potentials.

Ancillary