Cost analysis of colorectal cancer screening with CT colonography in Italy.

OBJECTIVE: Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy. METHODS: Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, per-participant to screening CTC, and per-subject with advanced neoplasia. RESULTS: Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of the entire screening CTC pathway was €196.80. Average cost per-participant for the screening invitation process was €17.04 and €9.45 for the pre-examination consultation process. Average cost per-participant of the CTC execution and reading process was €146.08 and of the diagnostic assessment colonoscopy process was €24.23. Average cost per-subject with advanced neoplasia was €3777.30. CONCLUSIONS: Cost of screening CTC was €196.80 per-participant. Our data suggest that the more relevant cost of screening CTC, amenable of intervention, is related to CTC execution and reading process.

Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test.

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22-28°C) and up to 60% at outside temperature (29°C, range 16-39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Reduced and Full-Preparation CT Colonography, Fecal Immunochemical Test, and Colonoscopy for Population Screening of Colorectal Cancer: A Randomized Trial.

BACKGROUND: Population screening for colorectal cancer (CRC) is widely adopted, but the preferred strategy is still under debate. We aimed to compare reduced (r-CTC) and full cathartic preparation CT colonography (f-CTC), fecal immunochemical test (FIT), and optical colonoscopy (OC) as primary screening tests for CRC. METHODS: Citizens of a district of Florence, Italy, age 54 to 65 years, were allocated (8:2.5:2.5:1) with simple randomization to be invited by mail to one of four screening interventions: 1) biennial FIT for three rounds, 2) r-CTC, 3) f-CTC, 4) OC. Patients tested positive to FIT or CTC (at least one polyp ≥6mm) were referred to OC work-up. The primary outcomes were participation rate and detection rate (DR) for cancer or advanced adenoma (advanced neoplasia). All statistical tests were two-sided. RESULTS: Sixteen thousand eighty-seven randomly assigned subjects were invited to the assigned screening test. Participation rates were 50.4% (4677/9288) for first-round FIT, 28.1% (674/2395) for r-CTC, 25.2% (612/2430) for f-CTC, and 14.8% (153/1036) for OC. All differences between groups were statistically significant (P = .047 for r-CTC vs f-CTC; P < .001 for all others). DRs for advanced neoplasia were 1.7% (79/4677) for first-round FIT, 5.5% (37/674) for r-CTC, 4.9% (30/612) for f-CTC, and 7.2% (11/153) for OC. Differences in DR between CTC groups and FIT were statistically significant (P < .001), but not between r-CTC and f-CTC (P = .65). CONCLUSIONS: Reduced preparation increases participation in CTC. Lower attendance and higher DR of CTC as compared with FIT are key factors for the optimization of its role in population screening of CRC.

The impact of immunochemical faecal occult blood testing on colorectal cancer incidence.

BACKGROUND: The efficacy of colorectal cancer screening based on faecal immunochemical test, in terms of reduction of colorectal cancer incidence, is under debate. In the district of Florence, an organized screening programme based on faecal immunochemical test has been running since the early 1990s. The aim of this study was to compare the risk of developing colorectal cancer for subjects undergoing faecal immunochemical test with those who did not undergo the test in the same period. METHODS: Two cohorts were analyzed: subjects who underwent an initial faecal immunochemical test between 1993 and 1999 ("attenders"), and unscreened residents in the same municipalities invited to perform the faecal immunochemical test in the same period ("non-attenders"). Kaplan-Meier and Cox regression analysis were performed to evaluate the risk of developing colorectal cancer. RESULTS: The attenders' and non-attenders' cohorts included 6961 and 26,285 subjects, respectively. Cox analysis showed a reduction in colorectal cancer incidence of 22% in the attenders' compared to the non-attenders' cohort (hazard ratio = 0.78, 95% Confidence Interval: 0.65-0.93). CONCLUSION: Our results support the hypothesis that screening based on a single faecal immunochemical test every 2 years produces a significant decrease in colorectal cancer incidence after an average follow-up observation period of 11 years.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study).

BACKGROUND: Colorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening. METHODS/DESIGN: A total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥ 6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC. DISCUSSION: This study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01651624.

Computed tomographic colonography in subjects with positive faecal occult blood test refusing optical colonoscopy.

BACKGROUND: Refusal of colonoscopy is a drawback of colorectal cancer screening programmes based on faecal occult blood test. Computed-tomographic-colonography is generally more accepted than colonoscopy. AIM: To compare adherence to computed-tomographic-colonography and second-invitation colonoscopy in subjects with positive faecal test refusing colonoscopy. METHODS: We performed a prospective study in 198 subjects with positive faecal test who refused first referral to colonoscopy in one endoscopy service of the Florence screening programme. Subjects were randomly invited to computed-tomographic-colonography (n = 100) or re-invited to colonoscopy (n = 98). Mail invitation was followed by a questionnaire administered by phone. Computed-tomographic-colonography findings were verified with colonoscopy. RESULTS: 32 subjects could not be reached, 71 (35.9%) had undergone colonoscopy on their own; 4 were excluded for contraindications; 30/48 (62.5%) in the computed-tomographic-colonography arm and 11/43 (25.6%) in the colonoscopy arm accepted the proposed examinations (p < 0.001). Four advanced adenomas and 1 cancer were found in the 28 subjects who ultimately underwent computed-tomographic-colonography and 2 advanced adenomas and 2 cancers in the 9 subjects who ultimately underwent second-invitation colonoscopy. CONCLUSION: Subjects with positive faecal occult blood test refusing colonoscopy show a higher adherence to computed-tomographic-colonography than to second invitation colonoscopy.

Familial risk of colorectal cancer in subjects attending an organised screening programme.

BACKGROUND: First degree relatives of colorectal cancer patients are at increased risk for the same disease. AIMS: To evaluate the prevalence of familial risk and its association with the occurrence of pathological significant lesions in subjects with positive faecal occult blood testing leading to colonoscopy. METHODS: Faecal occult blood testing is offered biennially to subjects aged 50-70. Subjects with a positive faecal test are invited to undergo colonoscopy. Familial history for colorectal cancer in subjects undergoing colonoscopy was routinely recorded. RESULTS: From 1995 to 2009, 4833 screenees with positive faecal occult blood test undergoing colonoscopy were enrolled. Twelve percent reported a positive first degree family history. Multivariate analysis evidenced that the probability of detecting pathological significant lesions was statistically associated with age, gender, type of test, repeated or first screening, and having at least 1 first degree relative with colorectal cancer. CONCLUSIONS: Subjects attending colonoscopy reporting a positive first degree family history are at increased risk for pathologically significant lesions.

Comparing different strategies for colorectal cancer screening in Italy: predictors of patients' participation.

OBJECTIVES: The objective of this study was to study predictors of patients' participation in colorectal cancer (CRC) screening. METHODS: Men and women, aged 55-64 years, were randomized to the following: (i) biennial fecal occult blood test (FOBT) delivered by mail (n=2,266); (ii) FOBT delivered by a general practitioner (GP)/screening facility (n=5,893); (iii) "once-only" sigmoidoscopy (FS) (n=3,650); (iv) FS followed by FOBT for screenees with negative FS (n=10,867); and (v) patient's choice between FS and FOBT (n=3,579). A stratified (by screening arm) random sample of attenders and nonattenders was contacted by trained interviewers 4 months after the initial invitation. Subjects giving their consent were administered a questionnaire (available online) investigating perceptions of individual CRC risk, attitudes toward prevention, adoption of health protective behaviors, and reasons for attendance/nonattendance. Adjusted prevalence odds ratios (ORs) were computed by multivariable logistic regression. RESULTS: The response rate was 71.9% (701 of 975) among nonattenders and 88.9% (773 of 870) among attenders. Adjusting for screening arm, center, gender, age, and education, participation was significantly higher among people who consulted their GP before undergoing screening (OR: 4.24; 95% confidence interval (CI): 3.11-5.78), who mentioned one first-degree relative with CRC (OR: 3.62; 95% CI: 2.02-6.49), who reported regular physical activity (OR: 1.85; 95% CI: 1.33-2.55), and who read the mailed information (letter only: OR: 1.85; 95% CI: 1.23-2.78; letter+leaflet: OR: 3.18; 95% CI: 2.12-4.76). People who considered screening to be ineffective (OR: 0.12; 95% CI: 0.08-0.19), those who considered it to be effective but reported even moderate levels of anxiety (OR: 0.32; 95% CI: 0.23-0.45), and those who mentioned previous knowledge of CRC screening tests were less likely to accept the invitation (OR: 0.49; 95% CI: 0.34-0.70). CONCLUSIONS: Adoption of health protective behaviors is associated with a higher attendance rate, whereas anxiety represents a strong barrier, even among people who deemed screening to be effective. Increasing the proportion of people who consult their GP when making a decision regarding screening might enhance participation.

Colorectal cancer mortality in two areas of Tuscany with different screening exposures.

Several randomized trials have demonstrated the efficacy of colorectal cancer screening by the fecal occult blood test in reducing colorectal cancer mortality, but an evaluation of population-based screening programs is still lacking. We compared the colorectal cancer mortality rates (both adjusted rates and 3-year moving average rates) during 1985-2006 for two geographic areas in the provinces of Florence and Prato in the Tuscany region of Italy that began active population-based screening for colorectal cancer at different times: the Empolese-Mugello district, in the early 1980s, and the rest of the Florence and Prato provinces, in early 2000. A log-linear Poisson model was used to estimate the annual percent change in mortality and to examine whether geographic area modified the effect of calendar year on it. The Empolese-Mugello district had a greater decrease in colorectal cancer mortality than the rest of the Florence and Prato provinces (estimated annual percent change in age-adjusted colorectal cancer mortality rate, 2.7% decrease per year [95% confidence interval {CI} = 1.7% to 3.7%] vs 1.3% decrease per year [95% CI = 0.8% to 1.7%], respectively). The interaction between calendar period and area was statistically significant (P < .001). Our results support the hypothesis that the implementation of colorectal cancer screening in the early 1980s in the Empolese-Mugello district, where approximately 17 500 people were tested each year with the fecal occult blood test, was associated with a larger reduction in colorectal cancer mortality than that observed in the rest of Florence and Prato provinces, where screening started 15-20 years later and where approximately 38 000 people were screened each year beginning in 2000.

Cost evaluation in a colorectal cancer screening programme by faecal occult blood test in the District of Florence.

OBJECTIVES: To evaluate the direct costs of first and repeat colorectal cancer screening by immunochemical faecal occult blood testing (I-FOBT). METHODS: Florence district residents aged 50-70 were invited to undergo one-time I-FOBT every two years. Full colonoscopy was recommended for FOBT-positive subjects. Direct cost analysis was carried out separately for the first and repeat screening. All relevant resources consumed by the programme were calculated. RESULTS: Among 25,428 or 62,369 subjects invited to the first or repeat screening, respectively, the corresponding participation rate was 47.8% or 52.3%, and the positivity rate was 4.4% and 3.3%. Corresponding detection rates and positive predictive values for cancer and advanced adenoma were 11.3% or 8.9% and 32.4% or 32.8%, respectively. The assessment phase accounted for the major cost, as compared with recruitment and screening. All cost indicators were slightly higher in the first screening compared with repeat screening. Cost per cancer and advanced adenoma detected was similar in the first or repeat screening. A higher than observed participation rate would have substantially reduced screening cost. CONCLUSION: Analysis of I-FOBT-organized population-based screening cost demonstrates lower cost at repeat compared with first screening and provides reference for decision-making in screening implementation.

CT colonography after incomplete colonoscopy in subjects with positive faecal occult blood test.

AIM: To report our experience with computed tomography colonography (CTC) systematically performed in subjects with positive faecal occult blood test (FOBT) and an incomplete colonoscopy in the setting of a population-based screening for colorectal cancer (CRC). METHODS: From April 2006 to April 2007, 43290 individuals (age range 50-70) who adhered to the regional screening program for the prevention of CRC underwent immunochemical FOBT. FOBT was positive in 1882 subjects (4.3%). 1463 (77.7%) of these subjects underwent colonoscopy, 903 performed in a single center. Of 903 colonoscopies 65 (7.2%) were incomplete. Forty-two of these subjects underwent CTC. CTC was performed with a 16-MDCT scanner after standard bowel prep (polyethyleneglycole) in both supine and prone position. Subjects whose CTC showed polyps or masses were referred to the endoscopist for repeat colonoscopy under sedation or underwent surgery. Per-lesion and per-segment positive predictive values (PPV) were calculated. RESULTS: Twenty-one (50%) of 42 CTCs showed polyps or masses. Fifty-five of these subjects underwent a repeat colonoscopy, whereas 2 subjects underwent surgery for colonic masses of indeterminate nature. Four subjects refused further examinations. CTC correctly identified 2 colonic masses and 20 polyps. PPV for masses or polyps greater than 9 mm was of 87.5%. Per-lesion and per-segment PPV were, respectively, 83.3% and 83.3% for polyps greater or equal to 10 mm, and 77.8% and 85.7% for polyps of 6-9 mm. CONCLUSION: In the context of a screening program for CRC based on FOBT, CTC shows high per-segment and per-lesion PPV for colonic masses and polyps greater than 9 mm. Therefore, CTC has the potential to become a useful technique for evaluation of the non visualized part of the colon after incomplete colonoscopy.

Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening.

BACKGROUND & AIMS: We conducted a study to estimate population coverage and detection rate (DR) achievable through different strategies of colorectal cancer (CRC) screening. METHODS: A population-based multicenter randomized trial comparing 3 strategies was used: (1) biennial immunologic fecal occult blood test (FIT), (2) "once only" sigmoidoscopy (FS), and (3) "once only" colonoscopy (TC). A random sample of men and women, aged 55 to 64 years, was drawn from general practitioners' (GP) rosters. Eligible subjects, randomized within GP, were mailed a personal invitation. Nonresponders in groups 2 and 3 were invited again at 12 and 24 months. Screenees with "high-risk" distal polyps (villous component >20%, high-grade dysplasia, CRC, size >or=10 mm, >2 adenomas) at FS, or with positive FIT, were referred for TC. RESULTS: The attendance rate was 32.3% (1965/6075) for FIT, 32.3% (1944/6018) for FS, 26.5% (1597/6021) for TC. FIT detected 2 patients with CRC (0.1%) and 21 with an advanced adenoma (1.1%). The corresponding figures were as follows: 12 (0.6%) and 86 (4.5%) patients, respectively, for FS; 13 (0.8%) and 100 (6.3%) patients, respectively, for TC. To detect 1 advanced neoplasm, it would be necessary to invite 264 people with FIT, 60 with FS, 53 with TC. FS would have detected 27.3% of the proximal advanced neoplasms detected at TC. Assuming the same participation rate at TC as at FS, 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS. CONCLUSIONS: When participants are offered 1 screening test, participation is lower in a TC than in an FS program. However, DR of advanced neoplasia is higher with TC.

Randomized trial of different screening strategies for colorectal cancer: patient response and detection rates.

BACKGROUND: Although there is general consensus concerning the efficacy of colorectal cancer screening, there is a lack of agreement about which routine screening strategy should be adopted. We compared the participation and detection rates achievable through different strategies of colorectal cancer screening. METHODS: From November 1999 through June 2001 we conducted a multicenter, randomized trial in Italy among a sample of 55-64 year olds in the general population who had an average risk of colorectal cancer. People with previous colorectal cancer, adenomas, inflammatory bowel disease, a recent (< or =2 years) colorectal endoscopy or fecal occult blood test (FOBT), or two first-degree relatives with colorectal cancer were excluded. Eligible subjects were randomly assigned, within the roster of their general practitioner, to 1) biennial FOBT (delivered by mail), 2) biennial FOBT (delivered by general practitioner or a screening facility), 3) patient's choice of FOBT or "once-only" sigmoidoscopy, 4) "once-only" sigmoidoscopy, or 5) sigmoidoscopy followed by biennial FOBT. An immunologic FOBT was used. Participation and detection rates of the strategies tested were compared using multivariable logistic regression models that adjusted for age, sex, and screening center. All statistical tests were two-sided. RESULTS: Of 28 319 people sampled, 1637 were excluded and 26 682 were randomly assigned to a screening arm. After excluding undelivered letters (n = 427), the participation rates for groups 1, 2, 3, 4, and 5 were 30.1% (682/2266), 28.1% (1654/5893), 27.1% (970/3579), 28.1% (1026/3650), and 28.1% (3049/10 867), respectively. Of the 2858 subjects screened by FOBT, 122 (4.3%) had a positive test result, 10 (3.5 per 1000) had colorectal cancer, and 39 (1.4%) had an advanced adenoma. Among the 4466 subjects screened by sigmoidoscopy, 341 (7.6%) were referred for colonoscopy, 18 (4 per 1000) had colorectal cancer, and 229 (5.1%) harbored an advanced adenoma. CONCLUSIONS: The participation rates were similar for sigmoidoscopy and FOBT. The detection rate for advanced neoplasia was three times higher following screening by sigmoidoscopy than by FOBT.

Interobserver agreement in the histologic diagnosis of colorectal polyps. the experience of the multicenter adenoma colorectal study (SMAC).

Current clinical practice guidelines for patients with colorectal polyps are mainly based on the histologic characteristics of their lesions. However, interobserver variability in the assessment of specific polyp characteristics was evaluated in very few studies. The purpose of this study was to evaluate the interobserver agreement of four pathologists in the diagnosis of histologic type of colorectal polyps and in the degree of dysplasia and of infiltrating carcinoma in adenomas. A stratified random sample of 100 polyps was obtained from the 4,889 polyps resected within the Multicentre Adenoma Colorectal Study (SMAC), and the slides were blindly reviewed by the four pathologists. Agreement was analyzed using kappa statistics. A median kappa of 0.89 (range 0.79-1.0) was estimated for the interobserver agreement for the diagnosis of hyperplastic polyp vs. adenoma. The agreement in the diagnosis of tubular, tubulovillous, and villous type, was given by median kappa values of 0.50, 0.15, and 0.36, respectively. The median kappa for the diagnosis of infiltrating carcinoma was 0.78 (range 0.73-0.84). Agreement on diagnosis of adenoma histologic subtypes, degrees of dysplasia, or infiltrating carcinoma in adenoma was moderate. A simpler classifications might help to better identify patients at different risk of colorectal cancer.

Role of double-contrast barium enema in colorectal cancer screening based on fecal occult blood.

AIMS AND BACKGROUND: Screening for colorectal cancer by fecal occult-blood testing has been shown to be effective in reducing colorectal cancer mortality. Total colonoscopy is the test of choice for the assessment of fecal occult blood-positive subjects. Double-contrast barium enema is commonly employed to study the rest of the colon when colonoscopy is incomplete. The present study evaluated the contribution of double-contrast barium enema in detecting neoplastic lesions of the colon in fecal occult-blood-positive subjects with incomplete colonoscopy. METHODS: In the frame of a screening program for colorectal cancer in the Florence District, a new immunochemical fecal occult-blood test replaced the classic guaiac fecal occult-blood test in 1993. Subjects with a positive fecal occult-blood test were invited to undergo total colonoscopy. Incomplete colonoscopy prompted double-contrast barium enema. Type and rate of neoplastic lesions detected by endoscopy or double-contrast barium enema as single methods or combined were evaluated. RESULTS: A total of 38,829 subjects underwent fecal occult-blood testing in the period 1993-2000. Overall, 1,542 were positive. Assessment was refused by 235 subjects. Out of 1,307 subjects accepting assessment, total colonoscopy was attempted in 1,294: of these, it was not possible in 343 cases, and double-contrast barium enema was advised and performed in 261 subjects. Colorectal cancer was detected in 115 subjects, single or multiple adenomas in 323, hyperplastic polyps in 58, inflammatory, hamartomatous or not histologically confirmed polyps in 38, and other benign non-polypoid findings or no abnormality in 773. There were significant differences between the rates of detected colorectal cancers or adenomas of total and incomplete colonoscopy. There were also significant differences between incomplete colonoscopy and the combination of incomplete colonoscopy and double-contrast barium enema as regards rates of detected colorectal cancer, and between total colonoscopy and the combination of incomplete colonoscopy with double-contrast barium enema as regards rates of detected adenomas. Double-contrast barium enema associated to incomplete colonoscopy was responsible for an increase in detection rates of cancer or adenoma of 2.3/1000 or 3.8/1000, respectively. CONCLUSIONS: Double-contrast barium enema was useful in detecting colorectal cancer beyond the range reached by incomplete colonoscopy, whereas our data confirmed a lower sensitivity of double-contrast barium enema for polyps. The diagnostic contribution observed in the present survey confirms the opportunity of performing double-contrast barium enema as a routine adjunct to incomplete colonoscopy. Nevertheless, in order to maximize the detection rate of adenomas, the rate of total colonoscopy should be kept as high as possible.