Impact on CRC Mortality of Screening Programs Based on FIT
Impact on CRC Mortality of Screening Programs Based on FIT
In the Veneto Region (Italy), which has about 4.9 million inhabitants, CRC is the second most common cancer (13% of all cancers) and the second most important cause of death from tumours (11%).
The Regional Health System is subdivided into 21 local health units (LHUs) which are the public agencies that organise and administer the health services, including screening programmes, in 581 municipalities. According to Italian law and in line with the recommendations of the European Council, population-based CRC screening programmes started in 2002 in the Veneto Region and are still being implemented. The screening programmes involve residents from 50 to 69 years of age who are invited via mail every 2 years to perform a single FIT, without any dietary restriction. Non-compliers with the first invitation are mailed a reminder, usually within 6 months. Most programmes use the OC-Hemodia latex agglutination test, developed with the OC-Sensor Micro instrument (Eiken, Tokyo, Japan), excluding one LHU which used FOB Gold (Sentinel Diagnostics, Milan, Italy) for the first 3 years.
Preanalytical and analytical aspects of the programmes are reported in online supplementary appendix 1, according to the Standard for Faecal Immunochemical TesTs for Haemoglobin Evaluation Reporting (FITTER) guidelines that have been recently proposed by the World Endoscopy Organization. Quantitative haemoglobin analysis is performed by automated instruments; the cut-off for test positivity is 20 μg Hb/g faeces (100 ng Hb/mL buffer). Subjects are notified of their results by mail and people with a negative FIT are advised to repeat the screening in 2 years. Subjects with a positive screening test are contacted by telephone to undergo a total colonoscopy (TC) performed at an endoscopic referral centre during dedicated sessions. Patients with screening-detected cancer are referred to surgery or surgical endoscopy and then enrolled in a follow-up programme.
FIT screening programmes were established in different LHUs between 2002 and 2009. The LHUs where screening was set up in 2002–2004 were classified as 'early screening areas' (ESA) and those where screening started in 2008–2009 as 'late screening areas' (LSA). All the following analyses have been restricted to the ESA and the LSA, thus excluding LHUs that instituted screening programmes between 2005 and 2007.
Death certificates are sent by each municipality to the LHU. Until 2005, causes of death were coded in each LHU according to International Classification of Disease (ICD)9. Since 2006, LHUs have transmitted a copy of the certificate to the Regional Epidemiological Department for coding of the underlying cause (using ICD10 since 2007) and entry into the electronic regional archive of causes of death.
The mortality records of residents in the Veneto Region in the period 1995–2011 were used to identify all deaths of subjects aged 50–74 years due to CRC (ICD9 153–154; ICD10 C18–C21). A sensitivity analysis was carried out adding codes for malignancy of the intestinal tract, part unspecified (ICD9 159.0, ICD10 C26.0).
The 70–74 age group was included in the analysis in order to account for the medium–long-term effect of screening on mortality (as well as incidence and surgery) rates, which is also expected to take place in older subjects who were screened in their 60s.
The Veneto Tumour Registry (VTR) covers 49% of the regional population (about 2.3 million inhabitants) and has been active since 1989. A case-resolution programme resolves more than half the diagnoses by evaluating the concordance among the three main sources (hospital discharge records, pathology records and death certificates). The remaining cases are ascertained through the consultation of medical charts.
All malignant incident cases are recorded according to the third version of the International Classification of Diseases for Oncology (ICD-O 3). Multiple primaries are coded according to the 2004 classification proposed by the International Association of Cancer Registries, the International Agency for Research on Cancer and the European Network of Cancer Registries. Incidence rates are available up to 2007. This analysis includes invasive CRC (ICD-X C18–21) diagnosed from 1995 to 2007 among subjects aged 50–74 years in the areas covered by the VTR (ESA: LHUs 2-Feltre and 13-Mirano; LSA: LHUs 3-Bassano del Grappa, 12-Veneziana and 19-Adria; figure 1).
(Enlarge Image)
Figure 1.
Map of local health units of the Veneto Region by period of activation of a colorectal screening programme.
The regional archives of hospital discharge records include all hospitalisations in regional hospitals as well as discharges of residents hospitalised outside the region, thus ensuring complete coverage of all major surgical procedures performed in the population. Discharge diagnoses and procedures are recorded according to the ICD, 9th edition—Clinical Modification.
All discharges from 1 January 2001 to 31 December 2012 of patients aged 50–74 years with a diagnosis of CRC (ICD9-CM diagnostic codes 153–154, 230.3, 230.4) and intervention codes 45.7–45.8 (colon resection) and 48.35, 48.5, 48.61–48.69 (rectal resection) were extracted. In the case of repeated admissions of the same subject with the selected codes, only the first hospitalisation was considered. Subjects already hospitalised for CRC surgery in 2000 were excluded from the analyses.
Crude and age-specific mortality, incidence and surgery rates were computed as the number of events per 100 000 people, with population data derived from the National Institute for Statistics (http://demo.istat.it/). Age-standardised rates were obtained by the direct standardisation method, taking the European standard population as reference.
A difference in mortality due to an earlier adoption of the screening programme was assessed by two Poisson regression models of CRC mortality rates. A first model examined three approximately equal calendar periods: before introduction of the screening programmes in the Veneto Region (1995–2000), and around (2001–2005) and after (2006–2011) the establishment of the screening programmes in the ESA; an interaction term between the study area and the calendar period explored any differences in the time change in CRC mortality rates between the ESA and the LSA.
Thereafter, a model of segmented Poisson regression was built assuming that a different trend in mortality could be observed immediately after the start of the screening programme in the ESA:
where the trend is a continuous variable equal to the years since the start of the study period. Change is a continuous variable that is the number of years since the intervention in 2002. The difference in change is equal to the change for the ESA and to 0 for the LSA; X is the set of other covariates in the model (age class and gender). According to this parameterisation, β1 corresponds to the difference in log-rates between the ESA and the LSA before the intervention, β2 corresponds to the common time trend in both areas before the intervention, β3 to the change in trend after 2002 in the LSA and β4 to the different change in trend in the ESA with respect to the LSA after 2002.
The above models were run in the total population aged 50–74 years adjusting for gender and 5-year age classes, and in men and women separately.
Methods
CRC Programmes in the Veneto Region
In the Veneto Region (Italy), which has about 4.9 million inhabitants, CRC is the second most common cancer (13% of all cancers) and the second most important cause of death from tumours (11%).
The Regional Health System is subdivided into 21 local health units (LHUs) which are the public agencies that organise and administer the health services, including screening programmes, in 581 municipalities. According to Italian law and in line with the recommendations of the European Council, population-based CRC screening programmes started in 2002 in the Veneto Region and are still being implemented. The screening programmes involve residents from 50 to 69 years of age who are invited via mail every 2 years to perform a single FIT, without any dietary restriction. Non-compliers with the first invitation are mailed a reminder, usually within 6 months. Most programmes use the OC-Hemodia latex agglutination test, developed with the OC-Sensor Micro instrument (Eiken, Tokyo, Japan), excluding one LHU which used FOB Gold (Sentinel Diagnostics, Milan, Italy) for the first 3 years.
Preanalytical and analytical aspects of the programmes are reported in online supplementary appendix 1, according to the Standard for Faecal Immunochemical TesTs for Haemoglobin Evaluation Reporting (FITTER) guidelines that have been recently proposed by the World Endoscopy Organization. Quantitative haemoglobin analysis is performed by automated instruments; the cut-off for test positivity is 20 μg Hb/g faeces (100 ng Hb/mL buffer). Subjects are notified of their results by mail and people with a negative FIT are advised to repeat the screening in 2 years. Subjects with a positive screening test are contacted by telephone to undergo a total colonoscopy (TC) performed at an endoscopic referral centre during dedicated sessions. Patients with screening-detected cancer are referred to surgery or surgical endoscopy and then enrolled in a follow-up programme.
FIT screening programmes were established in different LHUs between 2002 and 2009. The LHUs where screening was set up in 2002–2004 were classified as 'early screening areas' (ESA) and those where screening started in 2008–2009 as 'late screening areas' (LSA). All the following analyses have been restricted to the ESA and the LSA, thus excluding LHUs that instituted screening programmes between 2005 and 2007.
Mortality
Death certificates are sent by each municipality to the LHU. Until 2005, causes of death were coded in each LHU according to International Classification of Disease (ICD)9. Since 2006, LHUs have transmitted a copy of the certificate to the Regional Epidemiological Department for coding of the underlying cause (using ICD10 since 2007) and entry into the electronic regional archive of causes of death.
The mortality records of residents in the Veneto Region in the period 1995–2011 were used to identify all deaths of subjects aged 50–74 years due to CRC (ICD9 153–154; ICD10 C18–C21). A sensitivity analysis was carried out adding codes for malignancy of the intestinal tract, part unspecified (ICD9 159.0, ICD10 C26.0).
The 70–74 age group was included in the analysis in order to account for the medium–long-term effect of screening on mortality (as well as incidence and surgery) rates, which is also expected to take place in older subjects who were screened in their 60s.
Incidence
The Veneto Tumour Registry (VTR) covers 49% of the regional population (about 2.3 million inhabitants) and has been active since 1989. A case-resolution programme resolves more than half the diagnoses by evaluating the concordance among the three main sources (hospital discharge records, pathology records and death certificates). The remaining cases are ascertained through the consultation of medical charts.
All malignant incident cases are recorded according to the third version of the International Classification of Diseases for Oncology (ICD-O 3). Multiple primaries are coded according to the 2004 classification proposed by the International Association of Cancer Registries, the International Agency for Research on Cancer and the European Network of Cancer Registries. Incidence rates are available up to 2007. This analysis includes invasive CRC (ICD-X C18–21) diagnosed from 1995 to 2007 among subjects aged 50–74 years in the areas covered by the VTR (ESA: LHUs 2-Feltre and 13-Mirano; LSA: LHUs 3-Bassano del Grappa, 12-Veneziana and 19-Adria; figure 1).
(Enlarge Image)
Figure 1.
Map of local health units of the Veneto Region by period of activation of a colorectal screening programme.
Surgical Resections
The regional archives of hospital discharge records include all hospitalisations in regional hospitals as well as discharges of residents hospitalised outside the region, thus ensuring complete coverage of all major surgical procedures performed in the population. Discharge diagnoses and procedures are recorded according to the ICD, 9th edition—Clinical Modification.
All discharges from 1 January 2001 to 31 December 2012 of patients aged 50–74 years with a diagnosis of CRC (ICD9-CM diagnostic codes 153–154, 230.3, 230.4) and intervention codes 45.7–45.8 (colon resection) and 48.35, 48.5, 48.61–48.69 (rectal resection) were extracted. In the case of repeated admissions of the same subject with the selected codes, only the first hospitalisation was considered. Subjects already hospitalised for CRC surgery in 2000 were excluded from the analyses.
Statistical Analysis
Crude and age-specific mortality, incidence and surgery rates were computed as the number of events per 100 000 people, with population data derived from the National Institute for Statistics (http://demo.istat.it/). Age-standardised rates were obtained by the direct standardisation method, taking the European standard population as reference.
A difference in mortality due to an earlier adoption of the screening programme was assessed by two Poisson regression models of CRC mortality rates. A first model examined three approximately equal calendar periods: before introduction of the screening programmes in the Veneto Region (1995–2000), and around (2001–2005) and after (2006–2011) the establishment of the screening programmes in the ESA; an interaction term between the study area and the calendar period explored any differences in the time change in CRC mortality rates between the ESA and the LSA.
Thereafter, a model of segmented Poisson regression was built assuming that a different trend in mortality could be observed immediately after the start of the screening programme in the ESA:
where the trend is a continuous variable equal to the years since the start of the study period. Change is a continuous variable that is the number of years since the intervention in 2002. The difference in change is equal to the change for the ESA and to 0 for the LSA; X is the set of other covariates in the model (age class and gender). According to this parameterisation, β1 corresponds to the difference in log-rates between the ESA and the LSA before the intervention, β2 corresponds to the common time trend in both areas before the intervention, β3 to the change in trend after 2002 in the LSA and β4 to the different change in trend in the ESA with respect to the LSA after 2002.
The above models were run in the total population aged 50–74 years adjusting for gender and 5-year age classes, and in men and women separately.