{"doi":"10.1053/j.gastro.2023.06.035","title":"NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study","abstract":"Colonoscopy screening is a widely recommended method for detecting colorectal cancer (CRC) in countries across the world.1Schreuders E.H. et al.Gut. 2015; 64: 1637-1649Crossref PubMed Scopus (843) Google Scholar However, until recently, no randomized controlled trials demonstrated its effectiveness in average-risk individuals. Recently, Bretthauer et al2Bretthauer M. et al.N Engl J Med. 2022; 387: 1547-1556Crossref PubMed Scopus (149) Google Scholar published preliminary results of a multicenter randomized controlled trial, the Nordic-European Initiative on Colorectal Cancer (NordICC) trial, that investigated the effects of once-only colonoscopy screening on CRC incidence and mortality.2Bretthauer M. et al.N Engl J Med. 2022; 387: 1547-1556Crossref PubMed Scopus (149) Google Scholar In the intention-to-screen analysis, which compared participants not offered screening to those offered screening regardless of participation, they found that the invited group had an incidence and mortality reduction at 10 years of 18% and 10%, respectively. The investigators noted that although the incidence and mortality reductions were clinically important, they were lower than anticipated based on observational and modeling studies. The publication of the NordICC trial results induced media attention and controversy regarding the effectiveness of colonoscopies.3Krz S. et al.Nature. 2023; 613: 235-237Crossref PubMed Scopus (1) Google Scholar Experts advised people to interpret the results cautiously, noting aspects of the NordICC trial that could contribute to the underwhelming findings. A critical issue was the low screening uptake (42%). In the adjusted per-protocol analyses, which compared participants not offered screening to those offered screening who received colonoscopy, incidence and mortality reductions at 10 years increased to 31% and 50%, respectively. Another important consideration was the relatively short 10-year follow-up period. This study aimed to evaluate whether the NordICC trial results are lower than expected based on modeling and to what extent the results could be explained by screening uptake and follow-up period. We used 3 Cancer Intervention and Surveillance Modeling Network CRC models to simulate NordICC trial outcomes: Colorectal Cancer Simulated Population Model for Incidence and Natural History (CRCSPIN), Microsimulation Screening Analysis Colorectal Cancer (MISCAN-Colon), and Simulation Model of Colorectal Cancer (SimCRC). Using these models, we simulated the NordICC trial population,2Bretthauer M. et al.N Engl J Med. 2022; 387: 1547-1556Crossref PubMed Scopus (149) Google Scholar with 42% of the invited group simulated to receive a 1-time colonoscopy and a usual-care group remaining unscreened (Supplementary Table 1). Our modeling assumptions included random selection into screening unrelated to CRC risk, full adherence to US guidelines for adenoma surveillance,4Gupta S. et al.Gastrointest Endosc. 2020; 91: 463-485.e5Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar and high sensitivity of colonoscopy (Supplementary Materials). We compared model predictions to reductions in CRC incidence and mortality observed in the trial. Additionally, we simulated 5 hypothetical scenarios: 42% adherence with 15- and 20-year follow-up and 100% adherence with 10-, 15-, and 20-year follow-up. With 42% uptake and 10-year follow-up, the models predicted CRC incidence and mortality reductions of 11%–28% and 24%–32% (ranges are across models), respectively (Figure 1A and B). These estimates overlap the 95% confidence intervals (Cis) of the decreases observed in the NordICC intention-to-screen analyses, which were 18% (95% CI: 7–30) and 10% (95% CI: –16 to 36), respectively. The level of screening uptake had the largest impact on the findings: with 100% uptake, the model-predicted incidence and mortality reductions more than doubled to 26%–61% and 53%–70%, respectively (Figure 1C and D). These estimates compared wel","journal":"Gastroenterology","year":2023,"id":346369,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":776115,"name":"Pedro Nascimento de Lima","orcid":"0000-0001-9057-198X","position":1,"is_corresponding":false},{"id":995668,"name":"Amy B. Knudsen","orcid":"0000-0003-1872-996X","position":2,"is_corresponding":false},{"id":776114,"name":"Carolyn M. Rutter","orcid":"0000-0002-4396-8594","position":3,"is_corresponding":false},{"id":413839,"name":"David S. Weinberg","orcid":"0000-0002-2107-7651","position":4,"is_corresponding":false},{"id":282320,"name":"Iris Lansdorp‐Vogelaar","orcid":"0000-0002-9438-2753","position":5,"is_corresponding":false},{"id":6449,"name":"Ann G. Zauber","orcid":"0000-0002-1764-5994","position":6,"is_corresponding":false},{"id":986383,"name":"Anne I. Hahn","orcid":"0000-0003-4061-2303","position":7,"is_corresponding":false},{"id":271680,"name":"Fernando Alarid‐Escudero","orcid":"0000-0001-5076-1172","position":8,"is_corresponding":false},{"id":1074831,"name":"Christopher Maerzluft","orcid":"0000-0002-6027-0833","position":9,"is_corresponding":false},{"id":1087231,"name":"Alexandra Katsara","orcid":null,"position":10,"is_corresponding":false},{"id":418588,"name":"Karen M. Kuntz","orcid":"0000-0001-6335-7590","position":11,"is_corresponding":false},{"id":1087232,"name":"Merin John","orcid":null,"position":12,"is_corresponding":false},{"id":432510,"name":"Nicholson Collier","orcid":"0000-0002-2376-4156","position":13,"is_corresponding":false},{"id":381323,"name":"Jonathan Ozik","orcid":"0000-0002-3495-6735","position":14,"is_corresponding":false},{"id":965418,"name":"Luuk A. van Duuren","orcid":null,"position":15,"is_corresponding":false},{"id":986382,"name":"Rosita van den Puttelaar","orcid":"0000-0003-2216-6557","position":16,"is_corresponding":false},{"id":986925,"name":"Matthias Harlass","orcid":null,"position":17,"is_corresponding":false},{"id":711229,"name":"Claudia L. Seguin","orcid":"0000-0002-1076-5563","position":18,"is_corresponding":false},{"id":995705,"name":"Barak Davidi","orcid":"0000-0002-4802-0962","position":19,"is_corresponding":false},{"id":1086747,"name":"Carlos Pineda‐Antúnez","orcid":"0000-0002-8352-7080","position":20,"is_corresponding":false},{"id":218031,"name":"Eric J. Feuer","orcid":"0000-0003-4842-7751","position":21,"is_corresponding":false},{"id":385722,"name":"Lucie de Jonge","orcid":"0000-0001-5718-1058","position":22,"is_corresponding":false},{"id":1086746,"name":"D Berg","orcid":"0000-0003-0937-5274","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T01:11:48.317335Z","pmid":"37454978","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}