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      PSA kinetics before 40 years of age

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          ABSTRACT

          Purpose:

          The baseline PSA has been proposed as a possible marker for prostate cancer. The PSA determination before 40 years seems interesting because it not suffers yet the drawbacks related to more advanced ages. Considering the scarcity of data on this topic, an analysis of PSA kinetics in this period seems interesting.

          Materials and Methods:

          A retrospective assay in a database of a private diagnostic center was performed from 2003 to 2016. All subjects with a PSA before 40 years were included.

          Results:

          92995 patients performed PSA between the ages of 21 – 39. The mean value ranged from 0.66 ng / mL (at age 22) to 0.76 ng / mL (at age 39) and the overall mean was 0.73 ng / mL. As for outliers, 3783 individuals presented a baseline PSA > 1.6 ng / mL (p95). A linear regression model showed that each year there is a PSA increase of 0.0055 ng / mL (β = 0.0055; r 2 = 0.0020; p < 0.001). A plateau in PSA between 23 and 32 years was found and there were only minimal variations among the ages regardless of the evaluated percentile.

          Conclusion:

          It was demonstrated that PSA kinetics before 40 years is a very slow and progressive phenomenon regardless of the assessed percentile. Considering our results, it could be suggested that any PSA performed in this period could represent the baseline value without significant distortions.

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          Most cited references19

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          Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study

          Objective To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified. Design Case-control study with 1:3 matching nested within a highly representative population based cohort study. Setting Malmö Preventive Project, Sweden. Participants 21 277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years. Main outcome measures Metastasis or death from prostate cancer ascertained by review of case notes. Results Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group. Conclusion Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.
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            A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer.

            To evaluate the validity of prostate-specific antigen (PSA) in identifying men who subsequently were or were not clinically diagnosed with prostate cancer, assess optimal test cutoff, measure lead time, and estimate relative risks (RRs) associated with discrete PSA levels. Nested case-control study of men providing plasma samples before a 10-year follow-up. The Physicians' Health Study, an ongoing randomized trial that enrolled 22,071 men aged 40 to 84 years in 1982. A total of 366 men (cases) diagnosed with prostate cancer and 1098 men (three controls per case), matched by age, randomly selected from all cohort members at risk at the time of case diagnosis. Sensitivity and specificity for each year of follow-up and for aggressive and nonaggressive cancers separately. At a cutoff of 4.0 ng/mL, sensitivity for the entire 10-year follow-up was 46% for total cases. Sensitivities for detection of total, aggressive, and nonaggressive cancers occurring in the first 4 years were 73%, 87%, and 53%. Overall, specificity was 91% and changed little by year of follow-up. Optimal validity was achieved at a cutoff of 3.3 ng/mL. Estimated mean lead time for all cancers was 5.5 years. Only 40% of cancers detected more than 5 years from baseline were nonaggressive. Compared with men with PSA levels less than 1.0 ng/mL, those with PSA levels between 2.0 and 3.0 ng/mL had an RR of 5.5 (95% confidence interval, 3.7 to 9.2). A single PSA measurement had a relatively high sensitivity and specificity for detection of prostate cancers that arose within 4 years. Prostate-specific antigen values less than the usual cutoff were associated with substantial increases in risk compared with the lowest levels. Final evaluation of PSA screening must also consider cost and the ability of current treatments to improve the prognosis of screen-detected cases.
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              Genetic correction of PSA values using sequence variants associated with PSA levels.

              Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.
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                Author and article information

                Journal
                Int Braz J Urol
                Int Braz J Urol
                ibju
                International Brazilian Journal of Urology : official journal of the Brazilian Society of Urology
                Sociedade Brasileira de Urologia
                1677-5538
                1677-6119
                Nov-Dec 2018
                Nov-Dec 2018
                : 44
                : 6
                : 1114-1121
                Affiliations
                [1 ]Departamento de Urologia, Faculdade de Medicina do ABC, Santo André, SP, Brasil
                [2 ]Fleury Medicina e Saúde São Paulo, SP, Brasil
                [3 ]Departamento de Epidemiologia, Universidade de São Paulo, São Paulo, SP, Brasil
                Author notes
                Correspondence address: Cristiano Linck Pazeto, MD, Departamento de Urologia, Faculdade de Medicina do ABC, Rua: Dr. Henrique Calderazo, n° 321, Paraíso, 2° andar, São Paulo, SP, 09190-615, Brasil E-mail: cristianolinckpazeto@ 123456gmail.com

                CONFLICT OF INTEREST

                None declared.

                Article
                S1677-5538.IBJU.2017.0710
                10.1590/S1677-5538.IBJU.2017.0710
                6442185
                30325610
                316cb671-6cb5-4f45-8625-948b09bb9a8b

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 December 2017
                : 22 July 2018
                Page count
                Figures: 7, Tables: 3, Equations: 0, References: 17, Pages: 8
                Categories
                Original Article

                prostate-specific antigen,kinetics, prostatic neoplasms

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