Quality control on digital cancer registration.

Population-based cancer registration methods are subject to internationally-established rules. To ensure efficient and effective case recording, population-based cancer registries widely adopt digital processing (DP) methods. At the Veneto Tumor Registry (RTV), about 50% of all digitally-identified (putative) cases of cancer are further profiled by means of registrars' assessments (RAs). Taking these RAs for reference, the present study examines how well the registry's DP performs. A series of 1,801 (putative) incident and prevalent cancers identified using DP methods were randomly assigned to two experienced registrars (blinded to the DP output), who independently re-assessed every case. This study focuses on the concordance between the DP output and the RAs as concerns cancer status (incident versus prevalent), topography, and morphology. The RAs confirmed the cancer status emerging from DP for 1,266/1,317 incident cancers (positive predictive value [PPV] = 96.1%) and 460/472 prevalent cancers (PPV = 97.5%). This level of concordance ranks as "optimal", with a Cohen's K value of 0.91. The overall prevalence of false-positive cancer cases identified by DP was 2.9%, and was affected by the number of digital variables available. DP and the RAs were consistent in identifying cancer topography in 88.7% of cases; differences concerned different sites within the same anatomo-functional district (according to the International Agency for Research on Cancer [IARC]) in 9.6% of cases. In short, using DP for cancer case registration suffers from only trivial inconsistencies. The efficiency and reliability of digital cancer registration is influenced by the availability of good-quality clinical information, and the regular interdisciplinary monitoring of a registry's DP performance.

Non-compliance with colonoscopy after a positive faecal immunochemical test doubles the risk of dying from colorectal cancer.

BACKGROUND: The risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality. METHODS: The FIT-based CRC screening programme in the Veneto region (Italy) invited persons aged 50 to 69 years with a positive FIT (>20 µg Hb/g faeces) for diagnostic colonoscopy at an endoscopic referral centre. In this retrospective cohort study, we compared the 10-year cumulative CRC incidence and mortality among FIT positives who completed a diagnostic colonoscopy within the programme (compliers) and those who did not (non-compliers), using the Kaplan-Meier estimator and Cox-Aalen models. RESULTS: Some 88 013 patients who were FIT positive complied with colonoscopy (males: 56.1%; aged 50-59 years: 49.1%) while 23 410 did not (males: 54.6%; aged 50-59 years: 44.9%).The 10-year cumulative incidence of CRC was 44.7 per 1000 (95% CI, 43.1 to 46.3) among colonoscopy compliers and 54.3 per 1000 (95% CI, 49.9 to 58.7) in non-compliers, while the cumulative mortality for CRC was 6.8 per 1000 (95% CI, 5.9 to 7.6) and 16.0 per 1000 (95% CI, 13.1 to 18.9), respectively. The risk of dying of CRC among non-compliers was 103% higher than among compliers (adjusted HR, 2.03; 95% CI, 1.68 to 2.44). CONCLUSION: The excess risk of CRC death among those not completing colonoscopy after a positive faecal occult blood test should prompt screening programmes to adopt effective interventions to increase compliance in this high-risk population.

Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy.

OBJECTIVES: To ascertain if the use of hydroxychloroquine(HCQ)/cloroquine(CLQ) and other conventional DMARDs (cDMARDs) and rheumatic diseases per se may be associated with COVID-19-related risk of hospitalization and mortality. METHODS: This case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. The risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis comparing HCQ/CLQ vs MTX, vs other cDMARDs and vs non-use of these drugs. The presence of rheumatic diseases vs their absence in a non-nested population was investigated. RESULTS: A total of 1275 patients hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of MTX, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization [odds ratio (OR) 0.83 (95% CI 0.69, 1.00)] or mortality [OR 1.19 (95% CI 0.85, 1.67)] was observed. A lower risk was found when comparing HCQ/CLQ use with the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either MTX monotherapy [OR 1.19 (95% CI 1.05, 1.34)] or other cDMARDs [OR 1.21 (95% CI 1.08, 1.36)] vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. CONCLUSION: HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19-related outcomes. The use of other cDMARDs was associated with an increased risk when compared with non-use and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably due to immunosuppressive action.

Incidence of interval cancers in faecal immunochemical test colorectal screening programmes in Italy.

Objective In Italy, colorectal screening programmes using the faecal immunochemical test from ages 50 to 69 every two years have been in place since 2005. We aimed to measure the incidence of interval cancers in the two years after a negative faecal immunochemical test, and compare this with the pre-screening incidence of colorectal cancer. Methods Using data on colorectal cancers diagnosed in Italy from 2000 to 2008 collected by cancer registries in areas with active screening programmes, we identified cases that occurred within 24 months of negative screening tests. We used the number of tests with a negative result as a denominator, grouped by age and sex. Proportional incidence was calculated for the first and second year after screening. Results Among 579,176 and 226,738 persons with negative test results followed up at 12 and 24 months, respectively, we identified 100 interval cancers in the first year and 70 in the second year. The proportional incidence was 13% (95% confidence interval 10-15) and 23% (95% confidence interval 18-25), respectively. The estimate for the two-year incidence is 18%, which was slightly higher in females (22%; 95% confidence interval 17-26), and for proximal colon (22%; 95% confidence interval 16-28). Conclusion The incidence of interval cancers in the two years after a negative faecal immunochemical test in routine population-based colorectal cancer screening was less than one-fifth of the expected incidence. This is direct evidence that the faecal immunochemical test-based screening programme protocol has high sensitivity for cancers that will become symptomatic.

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.

Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.

BACKGROUND: The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. METHODS: The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. RESULTS: Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. CONCLUSIONS: Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+.

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

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9% were screen-detected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended.

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

We utilised the IMPATTO study's archives to describe the 2000-2008 colorectal cancer (CRC) incidence rate trends in Italy, once screening programmes based on the faecal immunochemical test were implemented in different areas. Data on CRCs diagnosed in Italy from 2000 to 2008 in subjects aged 40-79 years were collected by 23 cancer registries. Incidence rate trends were evaluated as a whole and by macro-area (North-Centre and South-Islands), presence of a screening programme, sex, ten-year age class, anatomic site, stage at diagnosis, and pattern of diagnosis (screen-detected, non-screen-detected). The annual percent change (APC) of incidence rate trends, with 95% confidence intervals (95%CI), were computed. The study included 46,857 CRCs diagnosed in subjects aged 40-79 years, of which 2,806 were screen-detected. The incidence rates in the North-Centre were higher than in the South and on the Islands. During the study period, screening programmes had been implemented only in the North-Centre and had a significant effect on incidence rates, with an initial sharp increase in incidence, followed by a decrease that started in the 3rd-4th years of screening. These incidence rate trends were exclusively due to modifications in the rates of stage I cases. After screening programmes started, incidence increased in all anatomic sites, particularly in the distal colon. The differential figures introduced by the implementation of screening programmes warrant a continuous surveillance of CRC incidence and mortality trends to monitor the impact of screening at a national level.

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

OBJECTIVE: Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. DESIGN: In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). RESULTS: Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). CONCLUSIONS: FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies.

Screening patterns within organized programs and survival of Italian women with invasive cervical cancer.

OBJECTIVES: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). METHODS: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. RESULTS: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC. CONCLUSION: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

Screening for colorectal cancer in Italy, 2009 survey.

We present the main results of the sixth 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 2009, 98 programmes were active, of which 13 had been activated during the year, and 59% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Eleven regions had their whole population covered. In the South of Italy and Islands, 4 new programmes were activated in 2009, with a theoretical extension of 22%. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime and FOBT for non-responders to FS. Overall, about 2,935,000 subjects were invited to undergo FOBT, 40% of those to be invited within the year. The adjusted attendance rate was 50% and approximately 1,426,000 subjects were screened. Large differences in the attendance rate were observed among regions, with 10% of programmes reporting values lower than 29%. Positivity rate of FOBT programmes was 5.6% at first screening (range: 2.5-12.4%) and 4.2% at repeat screening (range: 2.5-7.3%). The average attendance rate to total colonoscopy (TC) was 82.5%and in one region it was lower than 70%. Completion rate for total colonoscopy (TC) was 91.2%. Among the 631,460 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.4 for invasive cancer and 11.6 for advanced adenomas (AA - adenomas with a diameter ≥ 1 cm, with villous/tubulo-villous type or with high-grade dysplasia). As expected, the corresponding figures in the 824,562 subjects at repeat screening were lower (1.3‰ and 7.6‰ for invasive cancer and AA, respectively). The DR of cancer and adenomas increased with age and was higher among males. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FOBT+ subjects: in 16% of cases the waiting time was longer than two months. Nine programmes employed FS as the screening test: 65% of the target population (about 60,000 subjects) were invited and 9 511 subjects were screened, with an attendance rate of 24.3%. Overall, 81% of FS were classified as complete. Overall TC referral rate was 11% and the DR per 1,000 screened subjects was 2.6 and 43.7 for invasive cancer and AA, respectively.

Interval cancers in breast cancer screening: comparison of stage and biological characteristics with screen-detected cancers or incident cancers in the absence of screening.

AIMS AND BACKGROUND: To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen-detected cancers and "clinical" cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry. METHODS AND STUDY DESIGN: Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67). RESULTS: We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P=106), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10(-6)), pN (P = 10(-6)), grading (P = 10(-6)), estrogen receptors (P = 10(-5)), progesterone receptors (P = 10(-6)), and Ki67 (P = 10(-6)). CONCLUSIONS: Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis.

Screening for colorectal cancer in Italy: 2008 survey.

We present the main results from the fifth 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 2008, 87 programmes were active (14 had been activated during the year), and 52,9%of Italians aged 50- 69 years were residing in areas covered by organised screening programmes (theoretical extension). Ten Regions had their whole population covered. In the South of Italy and Islands, 12 new programmes were activated in 2008, including those of Abruzzo and Molise Regions, with an increase of theoretical extension from 7% to 21%. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime, or a combination of both. Overall, about 2,593,000 subjects were invited to undergo FOBT, 71%of those to be invited within the year. The adjusted attendance rate was 47.5% and approximately 1,171,000 subjects were screened. Large differences in the attendance rate were observed among Regions, with 10% of programmes reporting values lower than 30%. Positivity rate of FOBT programmes was 5.9% at first screening (range 2.0-11%) and 4% at repeat screening (range 2.9-6.5%). The average attendance rate for total colonoscopy (TC) was 81.3% and in three Regions it was lower than 70%. Completion rate of TC was 92.2%. Among the 665,264 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.7 for invasive cancer and 13.1 for advanced adenomas (AA, adenomas with a diameter ≥1 cm, with villous/ tubulo-villous type or with high-grade dysplasia). As expected, the corresponding figures in the 552,391 subjects at repeat screening were lower (1.3‰ and 8.3‰ for invasive cancer and AA, respectively). The DR of cancer and adenomas increased with age and was higher among males. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FOBT+ subjects: in 16.0% of cases the waiting time was longer than two months. Seven programmes employed FS as the screening test: 58.8% of the target population (about 50,000 subjects) were invited and 8,135 subjects were screened, with an attendance rate of 27.2%. Overall, 83% of FS were classified as complete. Overall TC referral rate was 13.5% and the DR per 1,000 screened subjects was 4.7 and 47.5 for invasive cancer and AA, respectively.