Interval colorectal cancers after negative faecal immunochemical test in a 13-year screening programme.

OBJECTIVE: To assess faecal immunochemical test sensitivity for cancer in a very large population-based cohort followed up for six rounds with biennial faecal immunochemical test repetition. METHODS: This study is based on interval colorectal cancers diagnosed in a cohort of subjects aged 50-69 undergoing repeated faecal immunochemical test screening (six rounds) from 2002 to 2015. Test sensitivity was calculated using both the Proportional Interval Cancer Rate and the Interval Cancer Proportion method. RESULTS: Among 441,647 faecal immunochemical tests (123,347 individuals), 150 interval colorectal cancers were detected after a negative faecal immunochemical test. Interval colorectal cancer incidence rate was 1.87 per 10,000 person-years (95%CI: 1.60-2.20), and it was higher during the second interval year (rate ratio: 1.78; 95%CI: 1.28-2.47), for proximal locations (rate ratio: 3.00; 95%CI: 1.92-4.68), and among 60-71 year old subjects (rate ratio: 2.37; 95%CI: 1.61-3.50). The Proportional Interval Cancer Rate was 13.1%, with an overall faecal immunochemical test sensitivity of 86.9% (95%CI: 84.7-89.0). Sensitivity was lowest at the first round (81.5%; 95%CI: 75.6-86.2), and increased to 91.9% (95%CI: 83.9-96.5) for subsequent rounds. Applying the Interval Cancer Proportion method, sensitivity was 83.9% (95%CI: 81.3-86.2), and it was highest at the first round (89.0%; 95%CI: 85.7-91.6), ranging between 73% and 83.1% at subsequent rounds. CONCLUSIONS: A faecal immunochemical test sensitivity for cancer higher than 80% resulted in a low incidence of interval colorectal cancers, representing an accurate estimate of one of the major limits of screening programmes. Due to intrinsic biases, the Proportional Interval Cancer Rate and the Interval Cancer Proportion methods generated different trends in faecal immunochemical test sensitivity by screening round.

Divergent Long-Term Detection Rates of Proximal and Distal Advanced Neoplasia in Fecal Immunochemical Test Screening Programs: A Retrospective Cohort Study.

Background: Short-term studies have reported that the fecal immunochemical test (FIT) is less accurate in detecting proximal than distal colorectal neoplasia. Objective: To assess the long-term detection rates for advanced adenoma and colorectal cancer (CRC), according to anatomical location. Design: Retrospective study. Setting: Population-based, organized screening program in the Veneto region of Italy. Participants: Persons aged 50 to 69 years who completed 6 rounds of FIT screening. Measurements: At each screening round, the detection rates for advanced adenoma and cancer, as well as the proportional interval cancer rate (PICR), were calculated by anatomical location (proximal colon, distal colon, or rectum). Results: Between 2002 and 2014, a total of 123 347 participants had 441 647 FITs. The numbers of advanced adenomas and cancer cases detected, respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal colon, and 1220 and 209 in the rectum. Although the detection rate for proximal colon cancer declined only from the first to the second screening round (0.63 to 0.36 per 1000 screenees), the rate for both distal colon and rectal cancer steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17 in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar trends were found for advanced adenoma (proximal colon, 5.32 in the first round to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]). Limitations: Participants with irregular attendance were censored. Those who had a false-positive result on a previous FIT but negative colonoscopy results were included in subsequent rounds. Conclusion: This FIT-based, multiple-round, long-term screening program had a negligible reduction in detection rates for neoplastic lesions in the proximal versus the distal colon after the first round. This was related to a higher PICR in the proximal colon and suboptimal efficacy in preventing the age-related proximal shifting of CRC. Primary Funding Source: None.

Impact of breast cancer screening in a population with high spontaneous coverage with mammography.

OBJECTIVE: The impact of organized screening programs on breast cancer (BC) mortality is unclear in an era of high spontaneous referral of women to mammography. The aim of this study was to analyze if the introduction of mammographic screening programs reduced BC mortality in the Veneto region, Italy, despite already widespread spontaneous access to mammography. METHODS: In Veneto, screening was introduced in different years between 1999 and 2009 across 21 local health units (LHUs), inviting asymptomatic women aged 50-69 years to undergo mammography biennially. We compared BC mortality for the 1995-2014 period of women aged 40-49 and 50-74 years who were resident in LHUs where screening programs started in 2003 (early LHUs) with women resident in LHUs where screening was introduced later (late LHUs). Poisson regression models were applied to incidence-based mortality (IBM), including only deaths from BC arising within the screening period. RESULTS: In the prescreening period and until 2010, BC mortality rates in early and late LHUs were similar in both age groups. In the last study period (2010-2014), we observed a 10% decrease in overall BC mortality in early compared to late LHU, limited to women aged 50-74 years. IBM was reduced by 8% (95% CI 1%-16%) in the overall study period and by 16% (6%-25%) in 2010-2014. CONCLUSIONS: In the Veneto region, screening programs were associated with a significant impact on BC-specific mortality; such effect appeared at least 8 years after screening implementation.

Long-term performance of colorectal cancerscreening programmes based on the faecal immunochemical test.

BACKGROUND: The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. METHODS: In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT. RESULTS: Over 12 years (2002-2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5‰ (95% CI 7.8 to 9.2), and 58.9‰ (95% CI 56.9 to 61.0), respectively. CONCLUSIONS: Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy.

Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy.

BACKGROUND AND STUDY AIMS: The high volume and poor palatability of 4 L of polyethylene glycol (PEG)-based bowel cleansing preparation required before a colonoscopy represent a major obstacle for patients. The aim of this study was to compare two low volume PEG-based preparations with standard 4 L PEG in individuals with a positive fecal immunochemical test (FIT) within organized screening programs in Italy. PATIENTS AND METHODS: A total of 3660 patients with a positive FIT result were randomized to receive, in a split-dose regimen, 4 L PEG or 2 L PEG plus ascorbate (PEG-A) or 2 L PEG with citrate and simethicone plus bisacodyl (PEG-CS). The noninferiority of the low volume preparations vs. 4 L PEG was tested through the difference in proportions of adequate cleansing. RESULTS: A total of 2802 patients were included in the study. Adequate bowel cleansing was achieved in 868 of 926 cases (93.7 %) in the 4 L PEG group, in 872 out of 911 cases in the PEG-A group (95.7 %, difference in proportions  + 1.9 %, 95 % confidence interval [CI]  - 0.1 to 3.9), and in 862 out of 921 cases in the PEG-CS group (93.6 %, difference in proportions  - 0.2 %, 95 %CI  - 2.4 to 2.0). Bowel cleansing was adequate in 95.5 % of cases when the preparation-to-colonoscopy interval was between 120 and 239 minutes, whereas it dropped to 83.3 % with longer intervals. Better cleansing was observed in patients with regular bowel movements (95.6 %) compared with those with diarrhea (92.4 %) or constipation (90.8 %). CONCLUSION: Low volume PEG-based preparations administered in a split-dose regimen guarantee noninferior bowel cleansing compared with 4 L PEG. Constipated patients require a personalized preparation. TRIAL REGISTRATION: EudraCT 2012 - 003958 - 82.

Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test.

OBJECTIVES: To assess the appropriateness of recommendations for endoscopic surveillance in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). DESIGN: 74 Italian CRC screening programmes provided aggregated data on the recommendations given after FIT-positive colonoscopies in 2011 and 2013. Index colonoscopies were divided into negative/no adenoma and low- risk, intermediate-risk and high-risk adenomas. Postcolonoscopy recommendations included a return to screening (FIT after 2 years or 5 years), an endoscopic surveillance after 6 months or after 1 year, 3 years or 5 years, surgery or other. We assessed the deviation from the postcolonoscopy recommendations of the European Guidelines in 2011 and 2013 and the correlation between overuse of endoscopic surveillance in 2011 and the process indicators associated with the endoscopic workload in 2013. RESULTS: 49 704 postcolonoscopy recommendations were analysed. High-risk, intermediate-risk and low-risk adenomas, and no adenomas were reported in 5.9%, 19.3%, 15.3% and 51.5% of the cases, respectively. Endoscopic surveillance was inappropriately recommended in 67.4% and 7%, respectively, of cases with low-risk and no adenoma. Overall, 37% of all endoscopic surveillance recommendations were inappropriate (6696/17 860). Overuse of endoscopic surveillance was positively correlated with the extension of invitations (correlation coefficient (cc) 0.29; p value 0.03) and with compliance with post-FIT+ colonoscopy (cc 0.25; p value 0.05), while it was negatively correlated with total colonoscopy waiting times longer than 60 days (cc -0.26; p value 0.05). CONCLUSIONS: In organised screening programmes, a high rate of inappropriate recommendations for patients with low risk or no adenomas occurs, affecting the demand for endoscopic surveillance by a third.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We present the main results of the 2011-2012 survey of the Italian screening programmes for colorectal cancer carried out by the National centre for screening monitoring (Osservatorio nazionale screening, ONS) on behalf of the Ministry of Health. By the end of 2012, 112 programmes were active, of which 11 had been activated during 2012 and 4 during 2011. The national theoretical extension increased from 66% of Italians aged 50-69 years residing in areas covered by organized screening programmes in 2010 to 73.7% in 2012. The majority of programmes employ the fecal immunochemical test (FIT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime and FIT for non-responders to FS. Overall, about 7,744,000 subjects were invited to undergo FIT, 53.1% of those to be invited within the two years. The adjusted attendance rate was 47.1%and 3,531,937 subjects were screened. Large differences in the attendance rate were observed among regions. Positivity rate of FIT programmes was 5.2% at first screening (range: 1.0-12.4%) and 4.0% at repeat screening (range: 3.4-6.4%). The average attendance rate to total colonoscopy (TC) was 81.2% and in two regions (Molise and Campania) it was lower than 70%. Completion rate for total colonoscopy (TC) was 91%. Among the 1,316,327 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.0 for invasive cancer and 9.1 ‰ for advanced adenomas (AA, adenomas with a diameter ≥1 cm, with villous/tubulo-villous type or high-grade dysplasia). As expected, the corresponding figures in the 2,215,610 subjects at repeat screening were lower (1.0‰ and 6.8‰ for invasive cancer and AA, respectively). Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FIT+ subjects: in 15% of cases the waiting time was longer than two months. Ten programmes in 2011 and eight in 2012 employed FS as the screening test: 24,549 subjects were screened in the two years, with an attendance rate of 24.5%. Overall, 85.9% of FSs were classified as complete. Overall, TC referral rate was 9.8% and the DR per 1,000 screened subjects was 3.0 and 48.2 for invasive cancer and AA, respectively.

Colorectal cancer screening of immigrants to Italy. Figures from the 2013 National Survey.

BACKGROUND: Colorectal cancer screening programmes in Italy invite 50-69-year-old residents for a faecal immunochemical test every two years, regardless of their citizenship. METHODS: The 2013 National Survey on Italian colorectal cancer screening programmes compared immigrants born in low- or middle-income countries with subjects who were born in Italy, by collecting aggregated data on compliance, faecal immunochemical test results, compliance with colonoscopy, detected lesions and stage at diagnosis separately for Italians and immigrants. RESULTS: Overall, 85 screening programmes invited 3,292,451 subjects, of whom 192,629 had been born abroad (5.9%). Compliance with invitation was lower in immigrants (34.3% vs. 51.3% in Italians), with p<0.001. Compliance was higher in females, regardless of the country of birth, in the youngest age group of immigrants but in the oldest of Italians. Immigrants showed a borderline excess of standardised faecal immunochemical test positivity rate at first screening (5.4% vs. 5.1% in Italians, p=0.05) and a significant excess at repeat screenings (4.8% vs. 4.4%, p=0.002). The detection rates for carcinoma and advanced adenomas were lower in immigrants than in Italians at first screening (respectively 1.34‰ vs. 1.62‰ and 8.41‰ vs. 9.25‰) - although the differences were not statistically significant - but not at repeat screening (respectively 1.06‰ vs. 0.98‰ and 6.90‰ vs. 6.79‰). CONCLUSIONS: Migrants showed a lower compliance with screening than Italians. The prevalence of neoplasia was lower at first screening and similar to the Italians' at repeat screenings.