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  • br Of note increased risk

    2020-08-18


    Of note, increased risk was seen with PSA levels of 1.1– 1.7 ng/ml at ages 40–54 yr, well within the “normal” range, and low enough not to trigger follow-up in usual clinical practice. These findings do not imply that prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, as this could lead to over-diagnosis, but that they undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible. This “smarter screening” approach may allow identification of men at high risk while reducing population-level harms through less intensive screening of very low-risk men [22].
    The new USPSTF recommendation applies to men aged 55–69 yr but acknowledges that men at higher risk, including African-American men and men with a family history, may wish to start screening earlier [1]. Similarly, guidelines from other organizations recommend screening begin at age 50 yr, while men at increased risk due to family
    Table 1 – Characteristics of prostate cancer cases and controls aged 40–64 yr, Southern Community Cohort Study
    Controls
    Cases Aggressive casesa (n = 91)
    Blood markers, median (IQR)
    Smoking status at baseline, n (%)
    Pack-years among ever smokers, mean 22.8
    Case characteristics
    Median age at diagnosis, yr (IQR)
    Median time to diagnosis, yr (IQR)
    Fatal cases
    AJCC stage at diagnosis, n (%)
    I
    II
    III
    IV
    Unknown
    Gleason grade at diagnosis, n (%)
    Unknown
    AJCC = American Joint Committee on Cancer; BMI = body mass index; DRE = digital rectal exam; IQR = interquartile range; PSA = prostate-specific antigen. a Aggressive prostate cancer: Gleason grade 7, or AJCC stage III or IV, or prostate cancer death.
    history or Y-27632 dihydrochloride may initiate screening at 40–50 yr [23,24]. However, midlife PSA predicts subsequent aggres-sive PCa better than either family history or race [25], suggesting that using midlife PSA level to determine on-going screening needs may be superior to these traditional risk factors.
    Only two studies of baseline PSA have included enough black men to compare results from white and black men. One small nested case-control study [9] in California found similar associations in white and black men between PSA levels at age 50 yr and risk of advanced stage PCa over 7 yr. 
    Another nested case-control study [11] in a different California population found that PSA at a median age of 34 yr was associated with increased risk of total and aggressive PCa over several decades, though loss to follow-up was high and outcome ascertainment somewhat incomplete [11].
    Our results are in line with those studies as well as with studies of the longer-term predictive value of baseline PSA among primarily white men in the USA [2,9–11,13] and Sweden [15,16]. We [2] and others have found substantially increased risk of PCa metastasis or death over 20–30 yr of
    Table 2 – Odds ratiosa]FID$T7[and 95% confidence intervals of the association between baseline total prostate-specific antigen in midlife and risk of total (n = 197) and aggressive (n = 91) prostate cancer among African-American men in the Southern Community Cohort study
    Total prostate cancer
    Aggressive prostate cancerc
    Age-specific total PSA percentilesb
    Age-specific total PSA percentilesb
    percentile percentile percentile percentile
    percentile percentile percentile percentile
    Excluding cases diagnosed within 2 yr of blood draw, age 40–64 yr
    Excluding cases diagnosed within 5 yr of blood draw, age 40–64 yr
    CI = confidence interval; OR = odds ratio; PSA = prostate-specific antigen. a Estimated using exact conditional logistic regression due to sparse data in some strata. Matching factors were age and community health center of enrollment.
    d Median unbiased estimate.
    Table 3 – Proportion of total and aggressive prostate cancers captured by percentiles of total PSA levels in controls by age group
    PSA level (ng/ml) Total prostate cancer, % Aggressive cancera,[7T$DIF]%
    PSA = prostate-specific antigen. a Aggressive prostate cancer:]FID$T7[Gleason grade 7 and above, or AJCC Stage III or IV, or prostate cancer death.
    follow-up for men with higher PSA at age 35–55 yr. Also in line with our results, these studies found that men with PSA below the median for their age had a very low long-term risk of aggressive PCa.
    Table 4 compares baseline PSA levels and the proportion of cases captured by different PSA categories between our study and results from the Physicians’ Health Study (PHS)