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102 Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews
  1. Theis Voss1,
  2. Mikela Krag1,
  3. Frederik Martiny1,2,
  4. Bruno Heleno3,
  5. Karsten Jørgensen4,5,
  6. John Brandt Brodersen1,6,7
  1. 1The Centre of General Practice in Copenhagen, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, Post box 2099, DK-1014 Copenhagen K, Denmark, Copenhagen, Denmark
  2. 2Center for Social Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark, Copenhagen, Denmark
  3. 3CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade Nova de Lisboa, Lisbon, Portugal, Lisbon, Portugal
  4. 4Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, JB Winsløwsvej 9b, 3rd Floor, 5000 Odense, Denmark, Odense, Denmark
  5. 5Open Patient data Exploratory Network (OPEN), Odense University Hospital, Odense, Denmark, Odense, Denmark
  6. 6The Research Unit for General Practice in Region Zealand, Øster Farimagsgade 5, Post box 2099, DK-1014 Copenhagen K, Denmark, Copenhagen, Denmark
  7. 7Research Unit for General Practice, Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Tromsø, Norway


The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration’s risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.

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