Risk factors for low-risk prostate cancer: A retrospective cohort study within the FinRSPC trial

Overdiagnosis of low-risk prostate cancer (PC), often accompanied by overtreatment, remains an important harmful consequence of prostate-specific antigen (PSA)-based screening. Although PSA screening can reduce PC mortality and metastatic PC, the balance of benefits and harms remains controversial. This retrospective cohort study of 80,144 men from the Finnish Randomized Study of Screening for Prostate Cancer, with a median follow-up of 18.0 years, compared determinants of low-risk PC with determinants of high-risk PC. Low-risk PC (N = 1774) was classified according to the European Association of Urology guidelines, excluding cases with subsequent PC death. A secondary analysis excluded cases with post-diagnosis disease progression. Intermediate, high-risk, and advanced cases were classified as high-risk PC (N = 6466). Poisson regression was used to analyze PC incidence. Low-risk PC was more common in the screening than the control arm (1.9 vs. 1.2 cases per 1000 person-years), whereas high-risk PC was more frequent in the control arm (5.7 vs. 5.4 cases per 1000 person-years in the screening arm). The risk of low-risk PC remained stable across screening rounds, while the risk for high-risk PC declined after the first screen. Age was associated with an increased risk of high-risk PC, but no clear trend by age was observed for low-risk PC. Family history and use of 5-alpha reductase inhibitors showed stronger associations with low-risk PC than high-risk PC, though less so for screen-detected cancers. These suggest that risk factors for low-risk PC differ from those for high-risk PC, with determinants of low-risk PC being more closely related to medical service use.