The detection of interval colorectal cancers following screening by fecal immunochemical test may predict worse outcomes and prompt ethical concerns: a 6-year population-based cohort study in a full district Corrado R. Asteria a , Giuseppe Lucchini b , Linda Guarda d , Paolo Ricci d , Mauro Pagani c and Luigi Boccia a The rates of colorectal cancer (CRC) interval surveyed in screen-detected patients using a fecal immunochemical test (FIT) are not negligible. The aim of this study was to assess the effect of interval cancer on outcomes compared with a population with cancer diagnosed after a positive test result. All patients between 50 and 71 years of age, who were residents of the Mantua district, affected by CRC and operated on from 2005 to 2010 were reviewed. Other than patient-related, disease-related, and treatment-related factors and tumor location, this population was differentiated as either participating or not to screening and then into populations developing interval cancer after a negative FIT result. Mortality was investigated by univariate analysis and by overall survival rates. The mean age of the 975 patients enrolled was 62 years (61.7% males). Most patients (n = 575, 59%) were not screen detected, and 400 (41%) were screen detected. Fifty-six (5.7%) patients in the latter group, representing 14% of the participants, developed interval cancer after a negative FIT result. Their cancer was mostly localized in the right colon (41.1%) instead of the left colon and rectum (P = 0.02). They also showed higher stages (P = 0.001), a moderate degree of differentiation (P = 0.001), and overall higher mortality rates than patients with cancer diagnosed after a positive test result (P = 0.001). The effect of interval CRC after screening with FIT resulted in worse outcomes compared with the FIT- positive group. With such findings, patients who had negative results for FIT should be informed of the risk of developing cancer within the rounds of screening to independently gain educational skills in the area of health prevention. European Journal of Cancer Prevention 00:000–000 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Cancer Prevention 2017, 00:000–000 Keywords: colon tumor location, fecal immunochemical test, interval colorectal cancer, overall survival rates, rounds of screening a Department of Surgery and Orthopaedics, General Surgery Unit, b Department of Healthcare Medical Management, Biostatistic Service, c Department of Medicine, Medicine Unit Pieve Coriano, Carlo Poma ASST and d Department of Epidemiology, Public Health Observatory, ATS Val Padana, Mantua, Italy Correspondence to Corrado R. Asteria, MD, Strada Lago Paiolo 10, 46100 Mantua, Italy Tel: + 39 0376 201246; fax: + 39 0376 201907; e-mail: corrado.asteria@asst-mantova.it Received 7 November 2016 Accepted 17 May 2017 Introduction The diagnosis of colorectal carcinoma (CRC) in its early stages does not always follow a linear pathway. In fact, the adherence to screening programs is still not optimal despite a positive trend in recent decades (Cole et al., 2013; Ventura et al., 2014), and the sensitivity and spe- cificity of tests can vary depending on tumor location. Currently, the evidence does not support the superior performance of a test than those currently available (Qaseem et al., 2012; National Colorectal Cancer Roundtable, 2013; Sugerman, 2013), whereas in clinical practice, the fecal immunochemical test (FIT) appears to have gradually replaced the guaiac-based fecal occult blood test, and other studies have demonstrated its superiority over guaiac-based fecal occult blood test (Brenner and Tao, 2013) and flexible endoscopy. Its worldwide acceptance is also supported in recent European guidelines (Halloran et al., 2012). In addition, a comprehensive review has noted the advantages and limitations of the method (Allison et al., 2014). Based on the collected cases, the design of this study arises from the need to verify the performance of the screening test adopted in our district using FIT. Furthermore, our first aim is to broaden the investigation toward the incidence of interval CRC (in the presence of negative FIT within more rounds) and compare the outcomes of this CRC group with a CRC group diagnosed with colonoscopy following a positive FIT result. Currently, studies described in this field are few but have shown a high rate of interval CRCs ∼ 21% (Gill et al., 2012). A secondary goal was focused on assessing whether diagnostic delays in patients owing to false-negative FIT result had affected outcomes by comparing the mortality rates of those patients with positive FIT result. A critical dis- cussion has ascertained issues on the role, benefits, This paper was presented as a Lunchtime Poster at the 11th Meeting of the European Society of Coloproctology (ESCP); 28–30 September 2016; Milan, Italy. Research paper 1 0959-8278 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/CEJ.0000000000000416 Copyright r 2017 Wolters Kluwer Health, Inc. 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