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

Abstract

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.

Keywords

Mass screening colorectal cancer faecal occult blood test sensitivity interval cancers

Introduction

Colorectal cancer (CRC) is the third leading cancer by incidence and the second by mortality in Italy.¹ Large randomised trials showed that screening with the Guaiac faecal occult blood test reduces mortality for CRC by more than 15%,² but the more sensitive and specific³ faecal immunochemical test (FIT) has now been adopted in most population-based screening programmes. The performance and effectiveness of screening programmes in part depend on the sensitivity of the screening algorithm, i.e. on the ability to identify cancers and pre-cancerous lesions that would otherwise produce symptoms in subsequent years. Screening programme sensitivity can be measured by comparing the incidence of interval cancers with the incidence of cancers in the absence of screening. This indicator does not require assumptions on the lead time (i.e. to what extent the diagnosis has been anticipated) and it is not influenced by potentially over-diagnosed cancers. However, it only makes sense when adopting a pre-fixed time frame and it cannot easily take into account the cancers occurring after the recommended interval and before the actual invitation due to delay and other organisational problems related to the programme.⁴ Studies on interval cancers give quite consistent estimates of the test sensitivity and proportional incidence in routine screening programmes, ranging from 73% to 82%.^5–8

In Italy, the implementation of organised CRC screening programmes started in 2005–2006, but the national scale-up has happened slowly and inconsistently. By 2013, active screening programmes covered about 79% of the Italian population, and about 62% were regularly invited.⁹ In 2008, the Ministry of Health funded a project for systematically evaluating the impact of screening programmes by merging screening and cancer registry archives (the IMPATTO study).^10,11

We examined the proportional incidence of interval cancers in Italian biennial FIT CRC screening, as estimated from the routine survey of the National Screening Monitoring Center and from cancer registry archives, completed with individual screening history.

Methods

Setting

The Italian guidelines recommend organised population-based screening programmes for CRC. The target population is aged 50–69, but in some regions this has been extended to age 74. Programmes may exclude from invitation people who had an invasive CRC or a recent documented colonoscopy. In this study, 5.5% were excluded from invitation, and 1.4% were excluded after presentation. The interval is two years. The OC-Hemodia latex agglutination test, developed with the OC-Sensor Micro instrument (Eiken, Tokyo, Japan), was used by all included programmes. The FIT positivity threshold is 100 ng Hb/mL. Subjects with a positive FIT are contacted to undergo a total colonoscopy, usually performed at an endoscopic referral centre. Patients with screen-detected neoplasms are treated endoscopically or referred for surgery, and then enrolled in a follow-up programme.

The oldest programme commenced in 1982, but most started after 2005. The implementation of screening programmes is almost complete in Northern and Central Italy, but in the South and Islands there are still large areas where programmes are not active, or invite a small proportion of the target population.⁹ Participation in the screening programmes included in this study from 2011 to 2012 ranged from 25% to 72% (average 45%).⁹ In Italy, cancer registries are not mandatory, but many local or regional health authorities have set up a register. In 2015, the population coverage was 53%.¹ The IMPATTO study collected data from CRC cases in subjects aged 40–79 that were diagnosed between 2000 and 2008 in the populations covered by 23 population-based cancer registries in 13 Italian regions.^10,11 Participation in the IMPATTO study was voluntary. Of 84 screening programmes active in 2008, 43 were in an area covered by a cancer registry. Only 16 pairs of cancer registries and screening programme coordinating centres participated in the IMPATTO study.

Data sources

All CRC cases (International Classification of Diseases, 10th revision: C18–C20) diagnosed during the study period in people aged 50–79 were collected. The inclusion criteria for cancer are described in detail elsewhere.¹⁰ The minimum core dataset included incidence date, morphology and topography, stage at diagnosis (according to Dukes’ classification as modified by Astler and Coller ¹²) and grading, surgical intervention, lymph nodes examined and positive lymph nodes. The tumour histological type was recorded according to the International Classification of Diseases for Oncology, 3rd edition. All the participating registries fulfilled quality criteria for inclusion in the IARC database,¹³ death certificate only cases for CRC being below 1%. Cancer registries and screening programmes linked the two databases to retrieve individual data on the screening history of patients before the incidence date by collecting the date of the first invitation and the dates of screening tests. Patients were then classified according to the following screening patterns:

screen-detected at the first screening episode;

screen-detected at a repeat screening episode;

screen-detected at follow-up, i.e. after a positive FIT, but detected after the first colonoscopy;

cancer in subjects with a positive screening FIT, but not compliant with diagnostic work-up;

interval cancers, i.e. cancer in subjects with at least one previous negative screening test;

cancers in subjects who have been invited but never participated (i.e. invited, but not tested within the screening programme);

never invited to screening.

Our study only includes interval cancers with an interval between the last negative test and the incidence of ≤24 months.

Denominators

Data on the number of negative tests performed each year by the screening programmes were collected through the survey conducted by the National Screening Monitoring Center. Surveys for CRC screening are available from 2005 and have been integrated by the coordinating centres of the SPs. The surveys collect data on the programmes’ target populations, invitations, test attendance and results, ascertainment, and final findings. The data are checked for consistency and completeness, in collaboration with the regional and local screening coordinating centres.

Reference incidence

Age- and sex-specific data on incidence in the year leading up to screening start were used to estimate the expected cases. For the Florence area, where the cancer registry started registration after screening implementation, we used the incidence estimated for the geographic macro area by the pool of Italian cancer registries at the beginning of the study period.

Data analysis

We classified cancers diagnosed within 12 months after negative screening as interval cancers 0–12, and those between 12 and 24 months as interval cancers 12–24. On the basis of the survey data, follow-ups of 12 and 24 months were defined for each screening programme and cancers with a screening test after the follow-up period were excluded. The cancers expected if screening had not taken place were calculated by applying the sex- and age-specific reference incidence rate to the number of negative tests recorded (person-years at risk) during follow-up. To determine the proportional incidence, the interval cancers were divided by the expected cancers. An overall 0–24 proportional incidence was estimated as the rate between the average incidence of interval cancer 0–12 and 12–24 and the expected incidence in the first year. We calculated 95% confidence intervals (CIs) assuming a Poisson distribution of the observed cases. The proportional incidence calculation is based on the assumption that subjects with a negative test were not re-tested before 24 months, and that screening tests were performed in the same calendar year as the screening invitation. We also assumed that the follow-up fixed at 12 or 24 months, together with the use of whole calendar years, does not require an equal distribution of calls during the calendar year. In addition, a likelihood-ratio test was used to determine whether the proportional incidence varied according to screening programme and anatomic site. After the application of these analysis criteria, three registries were excluded because they did not have one year of complete cancer registry follow-up after the activation of the screening programme.

Results

The available data for the IMPATTO study include 13 screening programmes for incidence in the first year after a negative screening test, and 11 for incidence in the second year (Figure 1), for a total of 579,176 and 226,738 screened people, respectively. In these populations, we observed 172 interval cancers, 100 in the first and 72 in the second year. The number of expected cancers was 794 in the first year and 317 in the second year, respectively. The overall proportional incidence was 13% (95% CI 10–15%) and 23% (95% CI 18–29%), respectively. Despite a higher incidence in the second year, the distribution of cancers by month in each year did not show a clear increasing trend as time elapsed following a negative test (Figure 2). The variability among programmes of proportional incidence is that expected due to random fluctuations (likelihood ratio test χ²= 13.57, df = 11, p = 0.2575) (Table 1). Women had a slightly higher proportional incidence in the second year, despite a similar absolute incidence of interval cancer, due to a lower expected incidence (Table 2). The proportional incidence was slightly lower in the distal colon than in the proximal colon and rectum, particularly in the second year after a negative test (p = 0.3914 and p = 0.0964 in the first year and second year, respectively) (Table 2). We estimated the overall 0–24 proportional incidence by averaging the value observed in the first year and the value observed in the second year. This estimate can be considered a direct indicator of one sensitivity of the screening algorithm. Overall, we estimated an 18% proportional incidence, 21% for females and 15% for males (p for heterogeneity = 0.02). No clear trend with age was detectable either in males or females. The screening protocol was more sensitive for distal cancers than for rectal and proximal cancers (Table 3).

Figure 1.

Years of screening activity and follow-up included in the study and number of yearly negative screening tests, by area. The boxed area represents the period of cancer registry data availability for each area; the dark grey area represents the years of screening activity (with relative numbers of negative tests per year) for which at least 24 months of follow-up are available and that are suitable for analysis of interval cancers in the first and second interval year; the light grey area represents the years of screening activity (with numbers of negative test) for which only 12 months of follow-up are available and are suitable only for the analysis of interval cancers in the first interval year; the striped area represents the last year of cancer registry data. All the screening programmes are continuing screening activity up to 2016.

Figure 2.

Distribution of interval cancers diagnosed in the first and second year after a negative screening test, by month.

Table 1.

Negative screening tests, expected cancers, observed interval cancers, and proportional incidence with 95% confidence interval in the first and second years after a negative test, by screening programme.

	First year after a negative test				Second year after a negative test
Screening programme	Negative tests	Expected cancers	Observed interval cancers	Proportional incidence (95% CI)	Negative tests	Expected cancers	Observed interval cancers	Proportional incidence (95% CI)
Milano	3041	5	1	0.20 (0.01–1.11)	–	–	–	–
Sondrio	19,160	22	3	0.14 (0.03–0.40)	9851	12	2	0.17 (0.02–0.60)
Biella	2253	4	0	0	–	–	–	–
Veneto	29,383	36	5	0.14 (0.05–0.32)	13,052	16	2	0.13 (0.02–0.45)
Bologna	58,791	88	12	0.14 (0.07–0.24)	5415	11	4	0.36 (0.10–0.93)
Piacenza	25,218	33	4	0.12 (0.03–0.31)	4101	6	0	0
Parma	53,272	68	8	0.12 (0.05–0.23)	41,282	53	10	0.19 (0.09–0.35)
Reggio Emilia	56,540	70	6	0.09 (0.03–0.19)	21,672	30	10	0.33 (0.16–0.61)
Modena	65,408	95	11	0.12 (0.06–0.21)	34,369	48	12	0.25 (0.13–0.44)
Ferrara	34,561	50	3	0.06 (0.01–0.18)	9721	14	0	0
Romagna	118,367	163	16	0.10 (0.06–0.16)	41,250	64	11	0.17 (0.09–0.31)
Firenze-Prato	59,782	82	12	0.15 (0.08–0.26)	40,054	55	21	0.38 (0.24–0.58)
Umbria	53,400	78	19	0.24 (0.15 –0.38)	5971	8	0	0
Total	579,176	794	100	0.13 (0.10–0.15)	226,738	317	72	0.23 (0.18–0.29)

Table 2.

	First year after a negative test				Second year after a negative test
	Negative tests	Expected cancers	Observed interval cancers	Proportional incidence (95%CI)	Negative tests	Expected cancers	Observed interval cancers	Proportional incidence (95%CI)
Gender and age (years)
Males
50–54	52,029	37	7	0.19 (0.08–0.39)	20,585	15	3	0.20 (0.04–0.58)
55–59	68,547	86	5	0.06 (0.02–0.14)	24,301	31	6	0.19 (0.07–0.42)
60–64	68,335	131	16	0.12 (0.07–0.20)	24,152	46	7	0.15 (0.06–0.31)
65–69	76,114	207	30	0.14 (0.10–0.21)	34,432	93	17	0.18 (0.10–0.29)
Total males	265,025	461	58	0.13 (0.10–0.16)	103,470	185	33	0.18 (0.12–0.25)
Females
50–54	64,670	37	2	0.05 (0.01–0.20)	24,709	14	5	0.36 (0.12–0.83)
55–59	81,701	72	6	0.08 (0.03–0.18)	29,061	25	5	0.20 (0.17–0.62)
60–64	78,835	88	17	0.19 (0.11–0.31)	29,244	32	11	0.34 (0.17–0.62)
65–69	88,945	136	17	0.13 (0.07–0.20)	40,254	61	18	0.30 (0.17–0.47)
Total females	314,151	333	42	0.13 (0.09–0.17)	123,268	132	39	0.30 (0.21–0.40)
Anatomic site
Proximal colon	579,176	216	30	0.14 (0.09–0.20)	226,738	86	25	0.29 (0.19–0.43)
Distal colon	579,176	300	32	0.11 (0.07–0.15)	226,738	120	20	0.17 (0.10–0.26)
Rectum	579,176	248	35	0.14 (0.10–0.20)	226,738	99	24	0.24 (0.16–0.36)
Colon NOS	579,176	31	3	0.10 (0.02–0.28)	226,738	12	3	0.25 (0.05–0.73)

Table 3.

Observed interval cancers and proportional incidence 0–24 months with 95% confidence interval, by age, gender, and anatomic site.

	Observed interval cancers	Proportional incidence (95%CI)
Males
50–54	10	0.20 (0.09–0.52)
55–59	11	0.13 (0.06–0.23)
60–64	23	0.14 (0.09–0.21)
65–69	47	0.16 (0.12–0.22)
Total males	91	0.15 (0.12–0.19)
Females
50–54	7	0.20 (0.08–0.42)
55–59	11	0.14 (0.07–0.25)
60–64	28	0.27 (0.18–0.38)
65–69	35	0.21 (0.15–0.29)
Total females	81	0.21 (0.17–0.26)
Anatomic site
Proximal colon	55	0.22 (0.16–0.28)
Distal colon	59	0.14 (0.10–0.18)
Rectum	52	0.19 (0.15–0.25)
Colon NOS	6	0.17 (0.06–0.37)
Total		0.18 (0.15–0.21)

Discussion

We followed up 579,176 and 226,738 people with a negative FIT for 12 and 24 months, respectively, and found a proportional incidence of 18%. Our results are consistent with those of previous studies, while being at the lower limit of the range.^5–8 In fact, the estimated proportional incidence ranged between 18% and 27% in other studies on FIT organised screening programmes with a biennial interval. We included in our denominator all the tests performed in people invited in the reference year, which possibly slightly overestimated the denominator and therefore the expected cases. Even if a slight underestimation of the proportional incidence of interval cancers is possible, all those studies showed very high sensitivity of FIT for invasive cancers leading to symptoms in the next two years. The sensitivity observed in our study is much higher than that reported for programmes using the Guaiac test.^14–18 These results are in line with the reported figures on the impact of FIT-based CRC screening programmes^19–23 that showed a much greater reduction of CRC incidence and mortality than that observed in the trials based on the Guaiac test.²

We also confirmed a higher sensitivity of FIT in males and a lower proportional incidence of interval cancers in the distal colon. These two observations are likely to be related. It has been reported that patients with proximal CRC are more often females than males^24,25 and that proximal CRC is a more aggressive type of tumour compared with distal CRC.^24,26 Proximal CRCs are more often flat, while distal tumours are polypoid-type, which is more detectable by FIT²⁷ and more distinguishable by colonoscopy.²⁸ This evidence may suggest that CRC screening in women requires greater test sensitivity. However, further evidence is needed to determine the most adequate gender-specific screening guidelines. Simply lowering the positivity threshold to identify a larger proportion of flat cancers (i.e. lesions with no evidence of a long pre-clinical phase and the presence of detectable pre-invasive lesions) would have minimal impact on test sensitivity, and no impact on screening efficacy.

Given the strong increase in CRC incidence with age, it is of note that the absolute risk of interval cancer increased with age, but screening sensitivity was substantially constant. As expected, we also found that interval cancer incidence was higher in the second year than in the first. The real risk of having a symptomatic cancer in the first year is probably lower than the risk we observed. In fact, the number of cancers diagnosed in the first month after the negative FIT was more than twice those observed in months 3–6. Some of these cancers could be due to preventive colonoscopies prescribed just after a negative FIT by some general practitioners or gastroenterologists who do not trust the faecal occult blood test.^29,30 Misclassification of the test result was excluded through an individual check of each case by the screening coordinating centres. Screening sensitivity showed little variability among centres, compatible with random fluctuations.

Although there are no international standards for the sensitivity for CRC of FIT-based screening programmes, our results indicate that the Italian programme screening protocol ensures a significant reduction in the risk of interval CRC. We recorded low levels of proportional incidence across all the evaluated subgroups (i.e. by gender, age class, anatomic site, screening programme), suggesting that there are no settings for which the performance of a screening based on biennial FIT is below acceptability levels. A possible exception may be the use of FIT in countries where high ambient temperatures may cause significant drops in haemoglobin concentration.^31–33 Our study could not evaluate the seasonal variation of proportional incidence, however, the impact of warming on the frequency of interval cancers has been shown to be limited.³⁴ Moreover, some manufacturers of FIT recently modified the buffer of their products to prevent haemoglobin degradation at high temperatures.³⁵

Strengths and limitations

In this, the first attempt to use routine National Screening Monitoring Center and cancer registry data to estimate the incidence of interval cancer in Italy, we did not need any individual data for the denominator, but only a characterisation of the cancers according to their screening history. We tried to define the proportional incidence of interval cancer using routine data that are now available in almost all the screening programmes where a cancer registry is active, a situation common to many European screening programmes.

The lack of data records at individual level for the person/time denominator introduces several limitations. First, we could not be certain that screening participants were not tested again within 24 months of a negative test, but as this would be exceptional, we assume that its effect on our results would be negligible, if any. Second, we could not assess the risk beyond the two-year interval because individual data on the actual re-invitation and related compliance were not available. Thus, we could not calculate the person-time for the denominator beyond the 24th month, when most people are expected to be invited for a new screening round. However, as the screening interval is two years, analysing the interval cancers diagnosed beyond the 24th month would be useful only to include in the proportional incidence interval cancers due to organisational problems of the programmes, i.e. delay in re-inviting the target population, but not to draw any general conclusion on the protocol screening interval. Furthermore, given the timing of the survey conducted by the National Screening Monitoring Centre, we possibly underestimated the proportional incidence of interval cancers, because we included in the denominator all the tests performed in people invited in the reference year, also including those who actually performed the test in the three months of the following year, while we only considered interval cancers with a negative test in the reference year. The effect of this limitation on our results could be particularly relevant for programmes contributing with only one or two years of screening. Because we combined all the study years in a single analysis, including undue subjects in the denominator only affects the last study year and is therefore diluted by the whole number of screened people in the entire study period. The median delay from invitation to test is about two months.³⁶ As the most recent periods of each year in our study population have higher risk because the tested population increased constantly during the study period, we are probably underestimating the incidence of interval cancers of the last year of observation by at least the cases occurring in 2 months out of 12, i.e. by about 17%. Not having individual data for the denominator also meant we could not take into account emigration and deaths that occurred during the follow-up, but as follow-up was very short (12 or 24 months), and with the relatively low emigration of the Italian population in that age group,³⁷ this bias should be limited.

This study only evaluated tests performed within organised screening programmes; opportunistic screening was not considered. Spontaneous screening for CRC in Italy is below 20%³⁸ and over the past 10 years has been almost exclusively based on colonoscopy. The anomalous peak of interval cancers in the first month after a negative FIT could be explained by opportunistic screening (i.e. some individuals who underwent screening and had negative results may be advised by their general practitioner to have a colonoscopy in any case, as a significant proportion of GPs do not trust faecal occult blood testing).²⁹ In general, the effect of opportunistic screening is to increase the incidence of interval cancers through the diagnosis of asymptomatic cancers that would otherwise be screen-detected at the following round.

Some further possible sources of bias exist. Our estimate of proportional incidence is strongly influenced by what we use as expected incidence in the absence of screening, i.e. the area-specific pre-screening incidence. For Florence, this reference incidence is quite chronologically distant from the study period, so if the underlying incidence has changed with time, there may be bias. We can note that, in the absence of screening, CRC incidence in Italy in the last decades showed a slight increasing trend for colon and no trend for rectum.³⁹ Another issue is the self-selection bias of screening participants. If participants have a different background risk from the whole population, we calculate the proportional incidence on the basis of the wrong expected incidence. This is possible as people with a recent colonoscopy, who could be at higher risk for familial CRC than the general population, can be excluded from invitation or have lower propensity to participate. Nevertheless, in the study period, very few people were excluded from invitation and at presentation. The last possible bias due to non-random or selective roll-out is that in some programmes people in their 68th or 69th year were invited first. This bias should be controlled by age-adjustment. Even though this was a national study, only 16 out of 42 programmes participated. This self-selection of the participants limits the generalisability of the results.

Conclusion

The incidence of interval cancers in the two years after a negative FIT in routine population-based CRC screening is about 20% of the expected incidence. This is a direct indicator of the high sensitivity of the screening protocol.

Colorectal Cancer Screening IMPATTO Working Group

Marco Zappa (Osservatorio Nazionale Screening; Istituto per lo studio e la prevenzione oncologica ISPO, Firenze); Emanuela Anghinoni (Gruppo italiano screening colorettale (GISCoR); Servizio medicina preventiva nelle comunità, ASL di Mantova); Carlo Senore (Centro per la Prevenzione Oncologica (CPO) Piemonte, Torino)

Siracusa: Francesco Tisano (Registro Tumori, Azienda Sanitaria Provinciale di Siracusa), Sabina Malignaggi (Centro Gestionale Screening Oncologici, Azienda Sanitaria Provinciale di Siracusa)

Veneto: Massimo Rugge (Department of Medicine DIMED Pathology and Cytopathology Unit, University of Padova, Padova; Registro Tumori del Veneto, Regione Veneto, Padova), Chiara Fedato (Coordinamento regionale screening, Regione Veneto, Venezia)

Trentino: Silvano Piffer, Roberto Rizzello (Registro Tumori di Trento, Servizio Epidemiologia Clinica e Valutativa, APSS, Trento)

Sassari: Flavio Sensi, Rosaria Cesaraccio (Struttura Complessa Pianificazione Strategica, Organizzazione, Governance, ASL n. 1 – Sassari)

Firenze: Gianfranco Manneschi (Istituto per lo studio e la prevenzione oncologica ISPO – Registro Tumori Toscano, Firenze); Grazia Grazzini (Istituto per lo studio e la prevenzione oncologica ISPO – Prevenzione secondaria e screening, Firenze)

Ferrara: Stefano Ferretti (Registro tumori AVEC, Azienda USL di Ferrara, Università di Ferrara), Aldo De Togni (Programmi di screening Azienda USL di Ferrara).

Bologna: Natalina Collina, Chiara Petrucci (Unità Operativa Epidemiologia Promozione della Salute e Comunicazione del Rischio- AUSL di Bologna)

Sondrio: Anna Clara Fanetti (Osservatorio Epidemiologico – Registro Tumori della Provincia di Sondrio, ATS della Montagna, Sondrio), Lorella Cecconami (Direzione sanitaria, ATS della Montagna, Sondrio)

Napoli: Mario Fusco, Maria Francesca Vitale (Registro Tumori Asl Napoli 3 Sud)

Catania-Messina: Marine Castaing, Anna Leone (Registro Tumori Integrato di CT-ME-SR-EN, Azienda Ospedaliero-Universitaria Policlinico Vittorio Emanuele, Catania)

Genova: Claudia Casella, Antonella Puppo (Registro Tumori Ligure, Epidemiologia Clinica, IRCCS AOU San Martino – IST, Genova)

Piacenza: Elisabetta Borciani, Pietro Seghini (Registro Tumori di Piacenza)

Umbria: Silvia Leite (Registro Tumori Umbro, Perugia); Morena Malaspina (Servizio di screening ASL Umbria 1, Perugia)

Friuli Venezia Giulia: Antonella Zucchetto (SOC Epidemiologia e Biostatistica, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano (PN))

Romagna: Orietta Giuliani, Silvia Mancini (Registro Tumori della Romagna, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC))

Latina: Fabio Pannozzo, Susanna Busco (Registro Tumori di Popolazione della Provincia di Latina, ASL Latina)

Modena: Claudia Cirilli, Gianfranco Di Girolamo (Registro Tumori di Modena)

Milano: Mariangela Autelitano (Registro Tumori di Milano), Enrica Tidone (Prevenzione oncologica, ASL di Milano)

Biella: Adriano Giacomin (Registro Tumori del Piemonte, Provincia di Biella), Alberto Azzoni (S.S. Gastroenterologia, ASL Biella)

Palermo: Walter Mazzucco (RTPP – Dipartimento Scienze per la Promozione della salute e materno infantile “G. D’Alessandro” Università di Palermo), Rosanna Cusimano (RTPP – UOC Sanità Pubblica Epidemiologia e Medicina Preventiva Azienda Sanitaria Provinciale di Palermo)

Reggio Emilia: Massimo Vicentini (Servizio Interaziendale di Epidemiologia AUSL di Reggio Emilia and Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia), Cinzia Campari (Staff Programmazione e Controllo, AUSL e IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia)

Parma: Maria Michiara, Paolo Sgargi (Registro Tumori di Parma)

Footnotes

Acknowledgement

The funder had no involvement in the study design, the collection, analysis and interpretation of data, the writing of the manuscript, or the decision to submit the article for publication.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Ministry of Health – Agenzia di Sanità Regione Abruzzo (grant 2008).

References

AIOM-AIRTum. I numeri del cancro in Italia 2015. Ed. Intermedia Editore. Brescia, 2015.

Hewitson

Glasziou

Irwig

et al.

Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007; 24: CD001216–CD001216.

Segnan

Patnick

von Karsa

. European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis, 1st ed. Luxembourg: Publications Office of the European Union, 2010.

Ciatto S, Naldoni C, Ponti A, et al. I carcinomi di intervallo quali indicatori di performance di un programma di screening. Modalità e standard per la valutazione. Osservatorio Nazionale per la Prevenzione dei Tumori, Sesto Rapporto, Firenze, 2007.

Campari

Sassatelli

Paterlini

et al.

Test and programme sensitivities of screening for colorectal cancer in Reggio Emilia. Epidemiol Prev 2011; 35: 118–124.

Castiglione

Visioli

Ciatto

et al.

Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening program. Br J Cancer 2007; 96: 1750e4–1750e4.

Zappa

Castiglione

Paci

et al.

Measuring interval cancers in population-based screening using different assays of fecal occult blood testing: the District of Florence experience. Int J Cancer 2001; 92: 151–154.

Zorzi

Fedato

Grazzini

et al.

High sensitivity of five colorectal screening programmes with faecal immunochemical test in the Veneto Region, Italy. Gut 2011; 60: 944–949.

Zorzi

Da Re

Mantellini

et al.

Screening for colorectal cancer in Italy: 2011–2012 survey. Epidemiol Prev 2015; 39: 93–107.

10.

Zorzi

Mangone

Anghinoni

et al.

Characteristics of the colorectal cancers diagnosed in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening. Epidemiol Prev 2015; 39: 108–114.

11.

Zorzi

Mangone

Anghinoni

et al.

Incidence trends of colorectal cancer in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening. Epidemiol Prev 2015; 39: 115–124.

12.

Astler

Coller

. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg 2003; 139: 846–852.

13.

Forman

Bray

Brewster

et al.

Cancer incidence in five continents, vol. X (electronic version), Lyon: International Agency for Research on Cancer, 2013. http://ci5.iarc.fr (accessed 12 November 2016).

14.

Tazi

Faivre

Lejeune

et al.

Interval cancers in a community-based programme of colorectal cancer screening with faecal occult blood test. Eur J Cancer Prev 1999; 8: 131–135.

15.

Steele

McClements

Watling

et al.

Interval cancers in a FOBT-based colorectal cancer population screening programme: implications for stage, gender and tumour site. Gut 2012; 61: 576–581.

16.

Gill

Bramble

Rees

et al.

Comparison of screen-detected and interval colorectal cancers in the Bowel Cancer Screening Programme. Br J Cancer 2012; 107: 417–421.

17.

Moss

Campbell

Melia

et al.

Performance measures in three rounds of the English bowel cancer screening pilot. Gut 2012; 61: 101–107.

18.

Garcia

Domenech

Vidal

et al.

Interval cancers in a population-based screening program for colorectal cancer in Catalonia, Spain. Gastroenterol Res Pract 2015; 2015: 672410–672410.

19.

Chiu

Chen

Yen

et al.

Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Cancer 2015; 121: 3221–3229.

20.

Giorgi Rossi

Vicentini

Sacchettini

et al.

Impact of screening programme on incidence of colorectal cancer: a cohort study in Italy. Am J Gastroenterol 2015; 110: 1359–1366.

21.

McClements

Madurasinghe

Thomson

et al.

Impact of the UK colorectal cancer screening pilot studies on incidence, stage distribution and mortality trends. Cancer Epidemiol 2012; 36: e232–e242.

22.

Ventura

Mantellini

Grazzini

et al.

The impact of immunochemical faecal occult blood testing on colorectal cancer incidence. Dig Liver Dis 2014; 46: 82–86.

23.

Zorzi

Fedeli

Schievano

et al.

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015; 64: 784–790.

24.

Benedix

Kube

Meyer

et al.

Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 2010; 53: 57–64.

25.

Pal

Hurria

. Impact of age, sex, and comorbidity on cancer therapy and disease progression. J Clin Oncol 2010; 28: 4086–4093.

26.

Hansen

Jess

. Possible better long-term survival in left versus right-sided colon cancer – a systematic review. Dan Med J 2012; 59: A4444–A4444.

27.

Rozen

Levi

Hazazi

et al.

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed. Aliment Pharmacol Ther 2009; 29: 906–917.

28.

Kaku

Oda

Murakami

et al.

Proportion of flat- and depressed-type and laterally spreading tumor among advanced colorectal neoplasia. Clin Gastroenterol Hepatol 2011; 9: 503–508.

29.

Federici

Giorgi Rossi

Bartolozzi

et al.

Survey on colorectal cancer screening knowledge, attitudes and practices of general practice physicians in Lazio, Italy. Prev Med 2005; 41: 30–35.

30.

Federici

Valle

Giorgi Rossi

et al.

Colorectal cancer screening: recommendations and guideline adherence by physicians from digestive endoscopy centers in the Lazio region – Italy. Prev Med 2006; 43: 183–186.

31.

Grazzini

Ventura

Zappa

et al.

Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district. Gut 2010; 59: 1511–1515.

32.

van Rossum

van Rijn

van Oijen

et al.

False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening. Int J Cancer 2009; 125: 746e50–746e50.

33.

Vilkin

Rozen

Levi

et al.

Performance characteristics and evaluation of an automated-developed and quantitative, immunochemical, fecal occult blood screening test. Am J Gastroenterol 2005; 100: 2519e25–2519e25.

34.

Zorzi

Baracco

Fedato

. Limited effect of summer warming on the sensitivity of colorectal cancer screening. Gut 2012; 61: 162–162.

35.

Grazzini G, Ventura L, Rubeca T, et al. Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test. Eur J Cancer Prev. Epub ahead of print 6 June 2016.

36.

Giuliani

Mancini

Vattiato

et al.

Survey al 31/12/2013 dello screening colorettale in Emilia-Romagna: analisi degli indicatori e dei trend temporali Collana Contributi Emilia-Romagna. 2016; 60: 101–112.

37.

ISTAT data, http://demo.istat.it/altridati/trasferimenti/index.html (accessed 22 December 2016).

38.

Giorgi Rossi

Federici

Bartolozzi

et al.

Understanding non-compliance to colorectal cancer screening: a case control study, nested in a randomised trial [ISRCTN83029072]. BMC Public Health 2005; 5: 139–139.

39.

AIRTum. Long-term cancer incidence and mortality trends, AIRTUM 1986-2005. Epidemiol Prev 2009; 33: S1: 106-118, http://www.registri-tumori.it/PDF/AIRTUM2009Trend/E&P33_4-5S1_105_trendstorici.pdf (accessed 18 September 2016).