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Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.

ABSTRACT: To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.Case-control study of men with and without prostate disease who were participants in a prospective aging study.Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively.The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.

SUBMITTER: Carter HB

PROVIDER: S-EPMC3461837 | biostudies-other | 1992 Apr 22-29

REPOSITORIES: biostudies-other

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Urinary prostate-specific antigen and microseminoprotein-beta levels in men with and without prostate cancer: A prospective cohort study.

Project description:IntroductionThe role of urinary proteomics in the diagnosis of prostate cancer (PCa) is undefined. Levels of urinary biomarkers such as prostate-specific antigen (PSA) and microseminoprotein-beta (MSMB) may differ between men with and without PCa. We tested this hypothesis using urine samples before and after digital rectal examination (DRE) in men with an indication for prostate biopsy.Materials and methodsIn an institutional ethics committee approved prospective cohort study, men with elevated PSA or a nodule on DRE underwent a pre- and post-DRE urine sample examination for urinary PSA and MSMB levels. Levels were compared between men who had PCa diagnosed on biopsy (Group A) and those with a negative biopsy (Group B).ResultsSeventy-seven patients were recruited of whom 32 had PCa (Group A) and 45 had no cancer (Group B) on biopsy. The median (interquartile range) serum PSA was 49.6 (0.2-254) ng/ml. The median urine PSA (29.5 vs. 26.4 mg/dl) and MSMB (1.7 vs. 2.4 mg/dl) were similar in both groups at baseline. However, post-DRE, both these metabolites rose in Group B but not in Group A, resulting in significantly higher post-to-pre values in Group B versus Group A. The post-DRE urine PSA/MSMB ratio was also significantly different between the groups.ConclusionsUrinary PSA and MSMB rose significantly after DRE only in men without PCa. Post-DRE urine PSA, MSMB, and PSA/MSMB ratio can differentiate PCa from benign pathology in men with an indication for prostate biopsy.

| S-EPMC6961425 | biostudies-literature

Total, free, and complexed prostate-specific antigen levels among US men, 2007-2010.

Project description:BACKGROUND:Screening for prostate cancer using prostate-specific antigen (PSA) is common. Prostate cancer has been associated with higher total PSA (tPSA), lower free PSA (fPSA), lower percent free PSA (%fPSA), and higher complexed PSA (cPSA). METHODS:Total, free and complexed PSAs were performed on 3251 men ?40years in the 2007-2010 National Health and Nutrition Examination Survey. Distributions of the PSA tests were examined by age, race and ethnicity, and body mass index (BMI) groups. Percentages of men at PSA thresholds were examined. RESULTS:Total PSA geometric mean was 0.96?g/l among men aged ?40years and increased from 0.74?g/l for men 40-49years, to 1.82?g/l for men 80years and older. Non-Hispanic Whites had lower age-adjusted mean tPSA (1.03?g/l) and cPSA (0.56?g/l) than non-Hispanic Blacks (tPSA 1.25?g/l and cPSA 0.72?g/l). Obese men had lower age-adjusted mean total, free and complexed PSAs (0.94, 0.27, and 0.51?g/l, respectively) than men with normal BMI (tPSA 1.21, fPSA 0.32, and cPSA 0.68?g/l, respectively). CONCLUSION:Total, free and complexed PSAs increased with age; tPSA and cPSAs were highest in non-Hispanic Blacks; and total, free, and complexed PSAs were lowest in obese men.

| S-EPMC7456738 | biostudies-literature

Variation in serum prostate-specific antigen levels in men with prostate cancer managed with active surveillance.

Project description:To describe fluctuations in prostate-specific antigen (PSA) levels in men managed with active surveillance (AS) to determine if a single PSA increase is a consistent measure to use to trigger intervention.We evaluated data on 541 patients undergoing AS between 1995 and 2011. PSA variation was described by studying the Kaplan-Meier probability of patients' PSA levels reaching 4 or 7 ng/mL, falling below those thresholds, and then rising to those thresholds again. We also examined PSA variation by calculating the Kaplan-Meier probability of a PSA change followed by an equal or greater change in the opposite direction.We analysed data on 541 patients undergoing AS with a median (interquartile range [IQR]) of 8 (6-12) PSA measurements and undergoing AS for a median (IQR) of 4 (2-6) years. The 5-year estimate of the probability of reaching a threshold PSA of 7 ng/mL was 40% (95% confidence interval [CI] 35-46%) and the 5-year estimate of subsequently falling below this threshold was 90% (95% CI 82-95%). The 5-year estimate of a PSA direction change was 95% (95% CI 93-97%) overall and 56% (95% CI 51-61%) for PSA direction changes of ?1 ng/mL.We observed a high probability of variability in PSA levels for patients on AS. The probability of changes in PSA, defined by an increase to the specified thresholds or a rise >1 ng/mL within 6 months and subsequent decrease of equal or greater value on a subsequent measurement, increases over time; therefore, a single change in PSA level is not a reliable endpoint for patients on AS.

| S-EPMC5523832 | biostudies-other

Overdiagnosis and Lives Saved by Reflex Testing Men With Intermediate Prostate-Specific Antigen Levels.

Project description:BackgroundSeveral prostate cancer (PCa) early-detection biomarkers are available for reflex testing in men with intermediate prostate-specific antigen (PSA) levels. Studies of these biomarkers typically provide information about diagnostic performance but not about overdiagnosis and lives saved, the primary drivers of associated harm and benefit.MethodsWe projected overdiagnoses and lives saved using an established microsimulation model of PCa incidence and mortality with screening and treatment efficacy based on randomized trials. We used this framework to evaluate four urinary reflex biomarkers (measured in 1112 men presenting for prostate biopsy at 10 US academic or community clinics) and two hypothetical ideal biomarkers (with 100% sensitivity or specificity for any or for high-grade PCa) at one-time screening tests at ages 55 and 65 years.ResultsCompared with biopsying all men with elevated PSA, reflex testing reduced overdiagnoses (range across ages and biomarkers = 8.8-60.6%) but also reduced lives saved (by 7.3-64.9%), producing similar overdiagnoses per life saved. The ideal biomarker for high-grade disease improved this ratio (by 35.2% at age 55 years and 42.0% at age 65 years). Results were similar under continued screening for men not diagnosed at age 55 years, but the ideal biomarker for high-grade disease produced smaller incremental improvement.ConclusionsModeling is a useful tool for projecting the implications of using reflex biomarkers for long-term PCa outcomes. Under simplified conditions, reflex testing with urinary biomarkers is expected to reduce overdiagnoses but also produce commensurate reductions in lives saved. Reflex testing that accurately identifies high-grade PCa could improve the net benefit of screening.

| S-EPMC7156927 | biostudies-literature

Sixteen-year longitudinal changes in serum prostate-specific antigen levels: the olmsted county study.

Project description:To determine the distribution of longitudinal changes in serum prostate-specific antigen (PSA) levels from a population-based sample of men.In this prospective cohort study, a random sample of Olmsted County, Minnesota, men aged 40 to 79 years in 1990 were followed up biennially from January 1, 1990, through August 29, 2007. Serum PSA levels were determined at each examination, and men were censored for follow-up with a diagnosis of prostate cancer or treatment for benign prostatic hyperplasia. The empirical distributions of annual percent change and annual absolute change in serum PSA level were calculated and tabulated, including the median and 75th and 95th percentiles.For men with PSA measurements 2 years apart, the median annual percent change in serum PSA level was 4.83% and the 95th percentile was about 49.76%. The variability in estimated annual change decreased with increasing time between assessments, with a 95th percentile of 21.82% after 8 or more years between assessments. Although the median absolute change per year increased with increasing age, the median percent change per year was fairly consistent across age groups.These data demonstrate that, with shorter intervals between assessments, greater variability should be expected. These distributions should prove helpful to patients and clinicians in interpreting changes in serum PSA levels observed in typical clinical practices.

| S-EPMC3538390 | biostudies-literature

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

Project description:OBJECTIVES:Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). SETTING, PARTICIPANTS AND OUTCOME MEASURES:Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. RESULTS:The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ?3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%,?respectively). CONCLUSION:A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. TRIAL REGISTRATION NUMBER:ISRCTN20141297,NCT02044172.

| S-EPMC5665300 | biostudies-literature

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

Project description:Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA.Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates.After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while ?-tocopherol (P=0.01), ?-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in ?-tocopherol and trans-?-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in ?-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only.Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence.

| S-EPMC4577465 | biostudies-literature

Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study.

Project description: Not available

| S-EPMC3253765 | biostudies-literature

Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer.

Project description:Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening.We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and ?-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa.Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the > 90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively.PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years.

| S-EPMC5019757 | biostudies-other

Evaluation of multiple risk-associated single nucleotide polymorphisms versus prostate-specific antigen at baseline to predict prostate cancer in unscreened men.

Project description:Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear.Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men.This study used a nested case-control design based on the Malmö Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005.We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer.Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p<0.001). Seven SNPs at five independent loci were associated with advanced prostate cancer defined as clinical stage?T3 or evidence of metastasis at diagnosis. Four independent SNPs were associated with advanced or aggressive cancer defined as stage?T3, metastasis, Gleason score?8, or World Health Organization grade 3 at diagnosis. Prostate cancer risk prediction with SNPs alone was less accurate than with PSA at baseline (area under the curve of 0.57 vs 0.79), with no benefit from combining SNPs with PSA. This study is limited by our reliance on clinical diagnosis of prostate cancer; there are likely undiagnosed cases among our control group.Only a few previously reported SNPs were associated with prostate cancer risk in the large prospective Diet and Cancer cohort in Malmö, Sweden. SNPs were less useful in predicting prostate cancer risk than PSA at baseline.

| S-EPMC3269546 | biostudies-literature

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