Prostate-specific antigen levels and subsequent prostate cancer: potential for screening.

Department of Epidemiology School of Hygiene and Public Health, The Johns Hopkins University, Baltimore 21205, USA.
American journal of epidemiology (Impact Factor: 5.59). 11/2008; 168(7):841-4. DOI: 10.1093/aje/kwn271
Source: PubMed

ABSTRACT Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 mug/liter compared to 2.4 mug/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 mug/liter compared to 1.3 mug/liter for controls (p = 0.0002). The sensitivity and specificity of a prostate-specific antigen level >/= 4mug/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively. Because prostate-specific antigen levels are reasonably sensitive and specific in detecting prostate cancer up to 6 years prior to the time of usual diagnosis, their use in screening for the prevention of prostate cancer mortality should be evaluated in a controlled clinical trial.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Strategies for the prevention of cancer include those aimed at reducing the incidence of cancer (primary prevention) and cancer mortality through early detection of tumors (secondary prevention). The efficacy of prevention interventions is evaluated by clinical trials. The conduct of clinical trials is aided by the use of serological indicators of the carcinogenic process measured using plasma or red or white blood cells. The accessibility and acceptability of obtaining blood samples for the measurement of serological markers of carcinogenesis permit widespread applications in the conduct of clinical trials. Serological markers must be shown to be valid and reliable before their use. Serological markers identify a variety of stages in the process of carcinogenesis such as inherited or acquired susceptibility to cancer, environmental exposures to carcinogens, biological effects of exposures, and the presence of preinvasive or invasive cancer. Serological markers may be used in clinical trials to select high risk but disease-free individuals for participation in clinical trials based on susceptibility factors or carcinogenic exposures. Other uses of serological markers include monitoring adherence to interventions and establishing trial outcomes of intermediate cancer end points or incident invasive disease. Examples of these applications are discussed. Serological markers of carcinogenesis have widespread applications in clinical research and potentially for clinical practice. Currently, the only limitation to their widespread use is the availability of validated serological markers. Because of the ease and acceptability of their use, research into the development of serological markers should continue. Methods for quickly validating serological markers should be developed in order to aid the transition to clinical applications.
    Cancer Research 05/1994; 54(7 Suppl):2011s-2014s. · 8.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND. The prostate specific antigen (PSA) gene has a polymorphic androgen response element (ARE) sequence with two alleles, A and G. PSA A-allele carriers have higher serum PSA levels in healthy men (HM). METHODS. We analysed DNA samples from 278 (556 alleles) unrelated individuals, 127 HM and 151 prostate cancer (PC) patients, for PSA ARE1 genotypes. RESULTS. The analysis of the frequencies from the 556 alleles indicates a significant overrepresentation of A-allele in the PC group under the age of 67 compared with the HM group (63.3% vs. 48.8%; P ¼ 0.009). We found that men carrying two A-alleles have increased risk for PC onset under the age of 67 (odds ratio [OR] ¼ 2.92; 95% confidence interval [CI], 1.10–7.86; P ¼ 0.013). Multivariate logistic regression analysis confirmed this association (OR ¼ 1.82; 95% CI, 1.03–3.22; P ¼ 0.037). Furthermore, the homozygosity for the A-allele was associated with higher serum PSA levels (P ¼ 0.027) and with the presence of circulating tumor cells in the blood of PC patients (P ¼ 0.018). CONCLUSION. Our results indicate that polymorphism in the PSA gene promoter may be an important biomarker for prostate cancer risk, especially for an earlier onset of PC. Prostate 53: 88–94, 2002. # 2002 Wiley-Liss, Inc.
    The Prostate 01/2002; 53:88-94. · 3.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.
    British Journal of Cancer 03/2000; 82(3):731-6. · 5.08 Impact Factor