Influence of follow-up, screening age, interval, and compliance on overdiagnosis of ductal carcinoma in situ (DCIS): a modelling study

Abstract Overdiagnosis estimates of ductal carcinoma in situ (DCIS) vary from 20-91%, which complicates screening communication and optimization. The aim was to quantify the influence of follow-up time and screening setting on overdiagnosis of DCIS. The fully validated micro-simulation Markov model for DCIS (SimDCIS) was used to estimate DCIS overdiagnosis in different screening settings with varying follow-up. DCIS overdiagnosis was defined as the number of diagnosed DCIS (screen-, clinically-detected, or progressed to invasive breast cancer) in screening that would not have been diagnosed without screening. Outcomes were presented as overdiagnosed proportion and rate. The base cohort was screened biennially from age 50-74 with 76% compliance and 25 years (y) follow-up and compared to the non-screened cohort. Follow-up was varied from 2-25y, screening start 40-74y, screening interval 1-5y and compliance 50-100%. DCIS overdiagnosis was estimated at 20% of all diagnosed DCIS and 38.1 overdiagnosed DCIS per 100,000 women screened biennially from age 50-74 at 76% compliance and 25y follow-up. The proportion of overdiagnosed DCIS increased with shorter follow-up (27% at 2y to 20% at 25y), older screening start age (1% at 40y to 15% at 74y), decreased screening interval (23% at 1y to 12% at 5y), and increased compliance (16% at half to 20% at full participation). In conclusion, reliable DCIS overdiagnosis estimates require attention to screening setting and ≥20 years follow-up. Older women (74y) showed up to seven times more overdiagnosis at initial screening than younger women (50y). Improved estimates can provide guidance in screening communication and optimization. Competing Interest Statement The authors have declared no competing interest. Funding Statement The author(s) received no specific funding for this work. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study used publicly available fully anonymized data, thus was exempt from ethical compliance and informed consent (confirmed non-WMO, M24.343483, Medical Ethics Review Board Groningen, The Netherlands). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The SimDCIS model v02 was used and is publicly available in GitHub at https://github.com/kp-gith/SimDCIS, in programming language C++.