title: Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?
abstract: After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations. We analyzed incidence data from the United States' Surveillance, Epidemiology, and End Results program for 1973-2010, comprising 511,027 prostate cancers in men ≥40 years old, and Norwegian national incidence data for 1953-2011, comprising 113,837 prostate cancers in men ≥50 years old. We developed a frailty model where only a proportion of the population could develop prostate cancer, and where the increased risk of diagnosis due to the massive use of PSA testing was modelled by encompassing this heterogeneity in risk. The frailty model fits the observed data well, and captures the changing age-specific incidence patterns across birth cohorts. The susceptible proportion of men is [Formula: see text] in the United States and [Formula: see text] in Norway. Cumulative incidence rates at old age are unchanged across birth cohort exposed to PSA testing at younger and younger ages. The peaking cohort-specific age-incidence curves of prostate cancer may be explained by the underlying heterogeneity in prostate cancer risk. The introduction of the PSA test has led to a larger number of diagnosed men. However, no more cases are being diagnosed in total in birth cohorts exposed to the PSA era at younger and younger ages, even though they are diagnosed at younger ages. Together with the earlier peak in the age-incidence curves for younger cohorts, and the strong familial association of the cancer, this constitutes convincing evidence that the PSA test has led to a higher proportion, and an earlier timing, of diagnoses in a limited pool of susceptible individuals.
authors.affiliation: Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. morten.valberg@medisin.uio.no.
authors.forename: Morten
authors.initials: M
authors.lastname: Valberg
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Grotmol
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Tretli
authors.affiliation: Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Marit B
authors.initials: MB
authors.lastname: Veierød
authors.affiliation: Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Department of Health Management and Health Economics, Institute of Health and Society, University of Oslo, Oslo, Norway.
authors.forename: Tron A
authors.initials: TA
authors.lastname: Moger
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Devesa
authors.affiliation: Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Odd O
authors.initials: OO
authors.lastname: Aalen
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D003431:Cross-Cultural Comparison; D004198:Disease Susceptibility; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000379:methods* / Q000706:statistics & numerical data; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D018426:SEER Program; D012680:Sensitivity and Specificity
chemical_list: D017430:Prostate-Specific Antigen
keywords: Frailty; PSA test; Prostate cancer; Susceptibility