Prostate Cancer Screening - Aspects of Overdiagnosis

Abstract: The overall aim of this thesis is to explore aspects of overdiagnosis, i.e. the diagnosis of a tumor that in the absence of screening would never have been diagnosed, in prostate cancer (PC) screening. The four papers in this thesis all emerge from the Göteborg randomized population-based PC screening trial, in which 10,000 men were invited to biennial prostate-specific antigen (PSA)-screening between 1995 and 2014 and 10,000 non-invited constituted a control group. In paper I, the accuracy of cause of death (COD) certificates, for men with PC, is evaluated by comparison with the COD as assigned by an independent committee after blinded review of medical records. Paper II assesses outcomes for men with screen-detected PC managed with, so called “active surveillance”. In paper III, organized screening is compared with opportunistic screening with respect to effectiveness in reducing PC mortality, measured as the number needed to invite (NNI) to screening and overdiagnosis, measured as number needed to diagnose (NND) to prevent one man from dying from PC. Paper IV investigates the risk of being diagnosed with PC depending on age at screening and the number of screens. The overall agreement between COD certificates and the committee was 96%. A large proportion of men screen-detected PC has low-risk PC (60%) and could safely be managed with active surveillance, at least with intermediate follow-up. Organized screening was more effective in reducing PC mortality and was associated with less overdiagnosis than opportunistic screening (NNI 139, NND 13 versus NNI 493, NNI 23). The risk of being diagnosed with PC increased dramatically with age but there was no apparent relation to the number of screens. From this thesis it can be concluded that Swedish COD certificates have a high accuracy and can be used for COD determination for men with PC, at least in the age-range studied (50-64 years old at the start of screening). Active surveillance appears safe for men with low-risk PC and should be used as a treatment strategy in order to reduce overtreatment. In order to reduce overdiagnosis and improve the benefit harm ratio of PC screening, screening should be conducted within the frameworks of an organized program where “younger” men could be screened relatively intense but where “older” men are screened more selectively.