Age-adjusted Prostate-specific Antigen Research Articles

Association of Obesity with Prostate Cancer at Time of Biopsy: A MultiCentre 10-Year Retrospective Study

Background and Aim: The incidence of Prostate cancer (PCa) is on the rise in Cameroon, making it the most commonly diagnosed cancer amongst men. Factors, such as obesity, smoking, and the consumption of high fat diet have been reported to play a role in the aetiology and progression of cancers in general. However, the exact relationship between obesity and prostate cancer in Africans is still poorly described. The present study aimed to evaluate the association between obesity as measured by the body mass index (BMI) and high-grade prostate cancer in Cameroonians. Methods: This was a retrospective analyses of the clinical records of 300 consecutive men who underwent transrectal ultrasound-guided core needle prostate biopsy between January 2010 and January 2020. Patients were grouped as obese (BMI ≥30kg/m²) and non-obese (BMI <30kg/m²) and binary logistic regression modelling was used to compare the association between obesity and patient characteristics, such as age, digital rectal examination (DRE) findings, prostate specific antigen (PSA) level, prostate volume, PSA density, and Gleason score (GS). Results: The mean age at diagnosis of PCa was 65.46 ± 8.54 years (Range: 34-89 years), the mean BMI was 28.93 ± 4.57 kg/m² (Range: 18.35-42.37 kg/m²), and the median total PSA level was 44.2 ng/ml. In total, 142 men (47.3%) were obese and biopsies detected high-grade prostate cancer in 160 men (63.3%). Obese men were significantly younger and had a higher risk (OR= 2.74, p <0.001) of having high-grade PCa compared to nonobese men. Furthermore, 94 obese men (58.75%) had high-grade PCa. Obese men had higher age-adjusted PSA densities (P<0.001), while there was no statistical difference in DRE findings (OR= 1.06, p= 0.225). Conclusion: This study demonstrated that obesity is associated with a higher risk of high-grade prostate cancer. This risk is more pronounced among younger patients and DRE findings are not influenced by BMI.

Prostate specific antigen-age volume score in predicting prostate cancer among the Indonesian population

Link of Video Abstract: https://youtu.be/ZNusQRjFEH0 Introduction: Several methods have been explored to increase the effectiveness of prostate-specific antigen (PSA) for prostate cancer screening. A lower prostate-specific antigen-age volume (PSA-AV) score is associated with higher cancer risk. This study aimed to evaluate the value of PSA-AV scores in the detection of prostate cancer among the Indonesian population. Methods: A retrospective study was conducted on 844 prostate biopsies performed at our center between January 2015 and December 2019. The score of PSA-AV was derived by multiplication of the patient's age and prostate volume and then division with PSA level. A ROC curve analysis was conducted to determine the cutoff for the PSA-AV score. The sensitivities and specificities of the PSA-AV score were contrasted with total PSA, PSA density, and age-adjusted PSA. Results: The mean age of the patient was 63.63±8.6 years, with a mean PSA of 16.3±13.9 ng/mL and a mean volume of 42.7±16.0 cm3. Among 844 biopsies, 25.5% tested positive for prostate cancer. Prostate cancer patients had significantly higher mean age, PSA levels, and positive digital rectal examinations (P<0.05). In predicting prostate cancer, the PSA-AV score demonstrated a higher AUC of 0.772, surpassing the AUC of 0.762 achieved by the total PSA. The analysis identified a cutoff of 700 for the PSA-AV score, which showed significant sensitivity (94%) and sufficient specificity (8.4%). These values outperformed the total PSA cutoff of 4 ng/mL (sensitivity 91.6%; specificity 5.4%), PSA density cutoff of 0.15 (sensitivity 85.1%; specificity 30.0%), and age-adjusted PSA cutoff (sensitivity 88.4%; specificity 11.8%). The superiority of the PSA-AV score of <700 was more prominent in the subgroup analysis of patients below 70 years of age and those with a low-moderate prostate volume (<60 cm3). Conclusions: The PSA-AV score demonstrated superior sensitivities and specificities compared to total PSA, PSA density, and age-adjusted PSA. Therefore, it is recommended to utilize a PSA-AV score of <700, particularly for men below 70 years of age with low-moderate prostate volumes (< 60 cm3).

A comparison of prostate health index, total PSA, %free PSA, and proPSA in a contemporary US population—The MiCheck-01 prospective trial

BackgroundIncreasing numbers of patients are presenting with aggressive prostate cancer (CaP); therefore, there exists a need to optimally identify these patients pre-biopsy. ObjectivesTo compare the accuracy of total prostate specific antigen (PSA), %free PSA, and prostate health index (PHI) to differentiate between patients without CaP, with non-aggressive (Gleason 3 + 3, non-AgCaP) and with aggressive (Gleason ≥ 3 + 4, AgCaP) in a contemporary US population. Design, settings, and participantsSerum samples were collected from 332 US patients scheduled for biopsy due to an elevated age-adjusted PSA. Site and Central biopsy pathologic assessment were performed. Outcome measurements and statistical analysisTesting of PSA, free PSA, proPSA, and PHI was performed along with central pathology review. Test performance using logistic regression analysis for differentiating CaP from non-CaP as well as non-AgCaP from AgCaP was evaluated. Results and limitationsCentral pathology review resulted in 32 upgrades including 14 Gleason 3 + 3 scores being upgraded to AgCaP with final distribution of 148 no-CaP, 64 non-AgCaP, and 120 AgCaP patients. Receiver operator curve (ROC) analysis of the different tests showed that PHI performed best at differentiating CaP from no-CaP subjects (area under the receiver operator curve 0.79). In contrast, the different tests were essentially equivalent in differentiating AgCaP vs. non-AgCaP. ConclusionsIn this recent US study of prebiopsy patients we observed a high proportion of AgCaP patients consistent with previous studies in contemporary US populations. Central Gleason review is recommended for multi-institutional studies comparing biomarkers. PHI was superior to PSA, free PSA, %free PSA, and proPSA in detecting CaP in this population but was not superior at differentiating AgCaP from non-AgCaP.

Pattern of age-adjusted serum prostate specific antigen reference intervals among men in Benin City, Nigeria

Prostate Cancer has assumed an important public health concern in Nigeria. Its incidence is anecdotally on the rise in our community and many prominent Nigerians are dying from it. The current study set out to ascertain the age adjusted prostate specific antigen (PSA) values indigenous to the local community and to confirm the relationship between PSA and age. In this study, enrollees were from a medical outreach carried out by a non-governmental agency in Benin City, Nigeria. The number of volunteers was 443 adult males. Eleven 11(2.48%) of this number were excluded from the study on account of their outlying PSA values. The mean age was 42.4years; the youngest volunteer being 18 years and the oldest, 86 years. The mean PSA value in the ≤40 year, 40-49, 50-59, 60-69, and ≥70year age categories were 1.77 ng/ml, 2.09 ng/ml, 1.99 ng/ml, 2.63 ng/ml, and 2.59 ng/ml respectively. The overall mean PSA was 2.21 ng/ml, whereas the median was 2.09ng/ml. Results showed positive but weak correlation between age and PSA (R = 0.161, P < 0.01). Nonetheless, significant increases in PSA with age were reported. The current study therefore provides a set of serum PSA values that are indigenous to the local environment, which could be used as cut-off threshold for performing prostatic biopsies.Keywords: prostate cancer, prostate specific antigen, glycoprotein, biopsy, Benin City

General practitioner perception of prostate-specific antigen testing has improved, but more awareness of prostate cancer risk in younger patients is still awaited.

BackgroundIn 2006, a county-wide survey of general practitioners (GPs) in the United Kingdom (UK) identified a reluctance to refer younger men with abnormal prostate specific antigen (PSA) levels. Younger men have the most to gain from early-detection of prostate cancer (PCa), which remains a national government priority in the UK and around the world. We sought to assess changes in perception of abnormal PSA-values amongst UK GPs over the past 10 years.Materials and methodsA total of 500 self-administered paper questionnaires were distributed to individually named GPs. One hundred and forty two responded (28.4%), representing a patient population of ∼600,000. A series of visual analogue questions assessed referral thresholds and understanding of risk factors related to the development of PCa.ResultsGPs with a median of 23-years experience responded. Although mean PSA threshold for referral to urology did fall between 2006 and 2016 in both the 45-year (5.42 ng/mL vs. 4.61 ng/mL P = 0.0003) and 55-year (5.81 ng/mL vs. 5.30 ng/mL P = 0.0164) age groups, the median referral values were unchanged. Significantly, referral thresholds quoted for younger men (<65 years) were considerably higher than recommended UK maximum PSA-levels. Using case-based scenarios, practitioners appeared more likely to refer older men with abnormal PSA values, with GPs reporting an average 56.2% likelihood of referring an asymptomatic 55-year-old with elevated age-adjusted PSA of 4.6 ng/mL. A total of 95.1% recognised a family history of PCa to be a potential risk factor but other at-risk categories were not so clearly understood.ConclusionAwareness of abnormal PSA values in UK primary care is improving, but continues to lag behind the evidence. Strategies to disseminate knowledge of maximum PSA-values to GPs should focus especially on those for younger patients.

Digital rectal examination in primary care is important for early detection of prostate cancer: a retrospective cohort analysis study.

Currently, there is no standardised screening for prostate cancer in Europe. Assessment of risk is opportunistically undertaken in consultation with the GP or urologist. Evaluation of the prostate gland consists of a prostate-specific antigen (PSA) serum level and a digital rectal examination (DRE) of the gland. DRE is an essential part of the assessment that can independently predict prostate cancer in the setting of a normal PSA level. To evaluate the clinical usefulness of the DRE in general practice and urology clinics, and to ascertain its positive predictive value and sensitivity. A retrospective analysis study of a cohort of Irish men who underwent TRUS guided biopsy of the prostate in a single Irish tertiary referral centre, despite a normal PSA level. Patients were identified from a Rapid Access Prostate Clinic patient database. Pathological biopsy results were correlated with clinical DRE findings. Patient demographics, PSA levels, and DRE findings from a prospectively established database and hospital data systems from May 2009 to October 2013 were analysed. Of 103 men referred over a 53-month period with a normal age-adjusted PSA level, 67% were referred on the basis of an abnormal DRE alone. Thirty-five per cent of males with a normal PSA had prostate cancer. DRE alone had a sensitivity and specificity of 81% and 40% respectively in diagnosing prostate cancer, with a positive predictive value of 42%. Seventy-six per cent of these men had high-grade disease. DRE is a key part of the assessment for prostate cancer. It can independently identify patients at risk of prostate cancer, with a substantial proportion of these having clinically significant disease requiring treatment. This study reinforces the importance of DRE in the primary care setting in the assessment for prostate cancer. An abnormal DRE, even in the setting of a normal PSA level, necessitates referral.

PSA Screening: A Discussion Based on the USPSTF Recommendations and the AUA and EAU Guidelines

The role of prostate-specific antigen (PSA) screening in the adult male population is not clearly defined. Although PSA has been shown to be the single most significant predictive factor for identifying men at increased risk of developing prostate cancer (PCa), PSA screening may lead to an increase in unnecessary prostate biopsies, significant over-diagnoses of PCa, and overtreatment of the disease, each of which may contribute to untoward complications and/or side effects. We reviewed PubMed and MEDLINE for articles published between 1970 to December 2013 that discuss the clinical applications of PSA as a screening test, in addition to clinical trials, evidence-based recommendations and guidelines from major medical organizations both in the U.S. and worldwide regarding prostate cancer screening. We also reviewed the current PSA screening recommendations of the United States Preventive Services Task Force (USPSTF), the American Urological Association (AUA), and the European Association of Urology (EAU). A total of 110 publications were reviewed. Results from the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and Göteborg trials regarding prostate screening are conflicting: The ERSPC and Göteborg trials show a reduction in prostate cancer mortality, but the PLCO trial shows no benefit. The USPSTF has assigned a grade D recommendation to PSA screening, that is, it has recommended against screening for men in the general U.S. population, regardless of age. The AUA updated its guideline in 2013 to reflect its belief that men under the age of 40 or over the age of 70 with less than a 10- to 15-year life expectancy should not be offered or subjected to PSA screening. Men between the ages of 40 and 54 with risk factors (positive family history or African American race), or men of average risk between the ages of 55 and 69 or older if life expectancy is greater than 10 years should be counseled on the risks and benefits of PSA screening and undergo PSA screening if desired. The EAU recommends obtaining a baseline PSA at age 40 to 45 and adapting subsequent screening intervals to that baseline. The diversity of methodology from randomized trials such as the PLCO, ERSPC, and Göteborg, allows for significant flexibility in interpretation, making it difficult to apply trial outcomes to substantiate universal recommendations. Clinical factors, such as age, race, family history, 10-year life expectancy, and patient preferences, should be taken into account. Variations on PSA-based screening, including age-adjusted PSA, PSA density (PSAD), PSA velocity (PSAV), and percentage of free PSA (%fPSA), may be used to improve the performance of the test. PSA testing may serve as the foundation for a more risk-based assessment. Finally, it should be noted that the decision to screen or not to screen using PSA testing is best made by the patient and his urologist after weighing its advantages and disadvantages.

Evaluation of Novel Formula of PSA, Age, Prostate Volume, and Race in Predicting Positive Prostate Biopsy Findings

To develop a formula that incorporates age, prostate volume, race, and prostate-specific antigen (PSA) level into a single score for prostate cancer detection. We developed a PSA-age volume (AV) score by multiplying the patient age by the prostate volume and dividing it by the PSA level. The PSA-AV was developed using 1000 prostate biopsy specimens and was validated on 318 internal and 4406 external biopsy specimens. We analyzed 1000 biopsy specimens (mean age 63 ± 8 years, 63% white and 35% black, mean PSA 6.8 ± 4 ng/mL, mean prostate volume 41 ± 18 cm(3), mean PSA-AV 485 ± 304). Of the 1000 biopsy specimens, 556 (55.6%) had positive findings. A lower PSA-AV score correlated with a greater cancer risk (R(2)= 0.91). A PSA-AV score of 700 had a sensitivity and specificity of 87% and 35%, respectively. These values matched or exceeded the sensitivity and specificity for age-adjusted PSA level and a PSA cutoff of 4 ng/mL. Compared with using the age-adjusted PSA level, using a score of 700 increased the number of biopsies by 64 and detected 62 more cancers. Using a PSA-AV cutoff of 700, rather than a PSA cutoff of 4 ng/mL, led to 16 fewer biopsies with 7 additional cancers detected. Our data were internally and externally validated. According to our data, a PSA-AV score has shown to be a useful formula for predicting positive biopsy findings. A PSA-AV score of 700 is useful in ruling out cancer in younger patients and patients with small prostates, and in ruling in cancer in older patients and patients with a large prostate.

Age-specific reference ranges for prostate-specific antigen among healthy Syrian men

Prostate-specific antigen (PSA) has become the most useful serum tumor marker in adjunct to digital rectal examination (DRE) for the management of prostate cancer (PC). The currently cited reference range of normal PSA levels (between 0 and 4.0 ng/mL) is deficient in terms of both sensitivity and specificity. Age-adjusted PSA have been proposed as an alternative to serum PSA. The primary objective of the present study is to determine the age-specific PSA and the percentage of free PSA (%FPSA) in healthy Syrian men. A total of 3,000 healthy Syrian men over 40 years old participated in this study. All men were asked to have total serum (TPSA) and free PSA (FPSA) tested, a DRE, and, when recommended, a prostate biopsy. Serum TPSA levels correlated with age (r=0.30, p<0.001). The 95th percentile TPSA values ranged from 1.7 ng/mL in the age group 40-49 years to 5.8 ng/mL in the group 70-80 years. The general pattern for medians and the percentile values for FPSA across age groups were similar to those seen for TPSA concentrations (r=0.37, p<0.001). However, the %FPSA was fairly constant across age groups except for the higher ratios in the youngest age group. These findings confirm that the serum TPSA and FPSA levels correlate with age. Interestingly, however, Syrian men have lower PSA values compared with other races. Racial differences of PSA concentrations were observed. Our results may help increasing the sensitivity and specificity of PSA measurements in the diagnosis of prostate cancer in Syria and probably in the surrounding regions.

The illusion of prostate‐specific antigen decline in patients with metabolic syndrome and insulin resistance

What's known on the subject? and What does the study add? Studies have shown that PSA is negatively associated with obesity as a result of hemodilution or metabolic effect. Hemodilution could be the main reason for low PSA levels in obese men. However, the intrinsic metabolic effects such as insulin resistance (IR) or metabolic syndrome (MS) on PSA level have not been clearly evaluated although obesity is closely tied to MS and IR. We regarded MS and IR as the pathophysiological cornerstone of metabolic disorder in obesity and analyzed the relationships among MS, IR, and PSA levels, and plasma volume by using the concept of PSA mass, the total circulating PSA protein. PSA mass did not change depending on the severity of the obesity, MS or IR. Even the group with both MS and IR, which could be the most metabolically disturbed in this study, did not have different PSA mass, comparing with the group without any MS or IR. Thus, the decline in PSA level in men with MS or IR can be also explained by increased plasma volume other than any intrinsic metabolic effects. • To investigate the detailed mechanism of prostate-specific antigen (PSA) decline in metabolic syndrome (MS) and insulin resistance (IR), which lowers the predictive value of the PSA test, we examined the effect of haemodilution and the possibility of an intrinsic metabolic effect. • We analysed 28,315 men who underwent routine check-ups. We compared the age-adjusted mean PSA levels in subjects with and without MS before and after adjusting or stratifying the plasma volume. We analysed changes in PSA level, plasma volume and PSA mass according to obesity grade, number of MS components, IR severity and diagnosis of MS, IR or both using an analysis of covariance. • The PSA levels were lower in the group with MS than in the group without MS (P= 0.001), but this difference disappeared after adjusting or stratifying the plasma volume (P > 0.05 for all). The PSA levels decreased, plasma volume increased, and PSA mass did not change as the number of MS components increased (P= 0.002, P < 0.001, P= 0.55, respectively) or the IR severity increased (P= 0.001, P < 0.001, P= 0.34, respectively). • Similarly, PSA levels were lower, plasma volumes were higher and PSA masses were the same in subjects with MS (P= 0.002, P < 0.001, P= 0.10, respectively), IR (P= 0.018, P < 0.001, P= 0.94, respectively), or both (P= 0.003, P < 0.001, P= 0.86, respectively) than in subjects without those conditions. • The PSA decline in MS and IR may result simply from a haemodilution effect and be unrelated to intrinsic metabolic disturbances. For this reason, PSA levels could be underestimated in patients with MS or IR because of haemodilution.

The effect of demographic and clinical factors on the relationship between BMI and PSA levels

Studies have reported lower prostate specific antigen (PSA) levels in men with a higher body mass index (BMI). Additional factors such as diabetes mellitus, benign prostatic hyperplasia (BPH) and certain medications may also affect PSA levels and confound the PSA-BMI association. In this study we evaluated the potential confounding effect of these factors on the obesity-PSA relationship and evaluated the association between these factors and PSA level. The study cohort consisted of 770 population-based controls without a history of prostate cancer (PCa) who participated in a prior PCa study. Demographic, anthropometric, and medical history data were obtained, and PSA level was determined from blood drawn at the time of interview. Linear regression was performed to evaluate the PSA-BMI relationship, adjusting for potential confounders. Finally, a forward stepwise algorithm was used to determine which factors were independently associated with PSA values. With increase in BMI (<25, 25-29, ≥30), the geometric mean PSA level declined (1.18, 1.13, and 0.94, respectively); obese men had a 17% (95% CI 0.70-0.99) lower age-adjusted PSA level compared to normal weight men. However, this relationship was non-significant (P = 0.17) in the multivariate model. Independent predictors of PSA level included age (β = 1.03, 95% CI 1.02-1.04), history of BPH (β = 1.48, 95% CI 1.27-1.72), current statin (β = 0.85, 95% CI 0.74-0.98), and NSAID use (β = 0.84, 95% CI 0.72-0.98). The relationship between obesity and PSA is confounded by a number of factors, which likely explain the observed inverse association previously reported. These results should help in interpreting PSA values in men screened for PCa.

Predictive Factors for Prostate Cancer in Biopsy of Patients with Prostate-Specific Antigen Levels Equal to or Less Than 4 ng/ml

PurposeThis study was conducted to identify the predictive factors for prostate cancer in patients with prostate-specific antigen (PSA) levels equal to or less than 4 ng/ml.Materials and MethodsA retrospective study of medical records was conducted on 292 patients with initial serum PSA ≤4 ng/ml among 2,305 patients who underwent prostate biopsy from January 2003 to December 2008. Prostate biopsy was performed on patients with PSA ≤4 ng/ml in the case of abnormal findings in the digital rectal examination (DRE) or transrectal ultrasonography (TRUS) or in those with a PSA level higher than the age-adjusted PSA levels. The patients were divided into the group diagnosed with prostate cancer and the non-prostate-cancer group. Subsequently, the variables of the two groups were compared.ResultsThe patients' mean age was significantly higher in the prostate cancer group (n=28) than in the non-prostate-cancer group (n=264; p=0.033). In addition, for the patients with a PSA range of 2.0-2.9 ng/ml, their age (p=0.049) and PSA density (PSAD; p=0.042) were significantly higher and the prostate volume (p=0.028) was significantly smaller in the prostate cancer group than in the non-prostate-cancer group.ConclusionsOf the patients with PSA ≤4 ng/ml, the age of the patients who showed abnormal findings in the DRE or TRUS or who had a PSA level higher than the age-adjusted PSA level was a significant predictive factor for prostate cancer. In particular, for the PSA range of 2.0-2.9 ng/ml, a thorough screening test for prostate cancer was required if the patients had conditions such as higher age, smaller prostate, and higher PSAD.

Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial

Decreased risk of advanced prostate cancer has been reported among men using statins. However, the evidence on overall prostate cancer risk is conflicting. We compared the relative risk between current users and non-users of statins or other cholesterol-lowering medications in a population undergoing systematical prostate cancer screening. The study cohort comprised of 23,320 men participating in the screening arm of the Finnish prostate cancer screening trial during 1996-2004. Information on medication use was obtained from a comprehensive national prescription database. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HRs) for prostate cancer. Serum prostate-specific antigen (PSA) level was compared between current users and non-users of cholesterol-lowering drugs. Compared with medication non-users, the overall prostate cancer incidence was decreased among statin users [HR 0.75, 95% confidence interval (CI) 0.63-0.89]. The inverse association was dose-dependent with cumulative amount of statin use, and strongest for low-grade and early stage tumors. The incidence was nonsignificantly lower also among users of other types of cholesterol-lowering drugs (HR 0.62, 95% CI 0.28-1.38), but without dose-dependence. Age-adjusted median serum PSA tended to be lower among users of cholesterol-lowering drugs, but the relative risk decrease among statin users was not related to decreased PSA. Overall incidence of prostate cancer was lowered among statin users when bias due to differential PSA testing between medication users and non-users was eliminated by systematical prostate cancer screening. Cholesterol-lowering with statins seems beneficial for prostate cancer prevention.

2059 THE EFFECT OF DEMOGRAPHIC AND CLINICAL FACTORS ON THE RELATIONSHIP BETWEEN BMI AND PSA LEVELS

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20102059 THE EFFECT OF DEMOGRAPHIC AND CLINICAL FACTORS ON THE RELATIONSHIP BETWEEN BMI AND PSA LEVELS Jonathan L. Wright, Daniel W. Lin, and Janet L. Stanford Jonathan L. WrightJonathan L. Wright More articles by this author , Daniel W. LinDaniel W. Lin More articles by this author , and Janet L. StanfordJanet L. Stanford More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2106AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Studies have reported lower prostate specific antigen (PSA) levels in men with a higher body mass index (BMI). Additional demographic and clinical factors may also affect PSA levels and are related to obesity, including diabetes mellitus (DM), benign prostatic hyperplasia (BPH) and certain medications (e.g., statins, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs)). In this study, we determine whether, when controlling for BMI, other factors are independently associated with PSA levels in healthy men. METHODS 787 controls from a population-based case-control study of prostate cancer (PCa) comprised the study cohort. PSAs were drawn at time of interview and log-transformed for analysis. Demographics and medical history were obtained. Participants were asked specifically about statin, NSAID and aspirin use. BMI was categorized (<25, 25″C29, ¡Ý30) and age-adjusted linear regression used to predict geometric mean PSA level. A multivariate stepwise regression model was used to explore potential confounders (race, family history of PCa (FH), BPH, DM and current medication use). RESULTS With increasing BMI (<25, 25″C29, ¡Ý30), the geometric mean PSA level declined (1.20, 1.14, 0.91 respectively) and obese men had a 20% reduction in geometric mean PSA compared to those with normal weight (95% CI 67%″C95%), adjusting for age. Multiple variables were statistically significantly associated with decreases (statin use, aspirin use, DM) or increases (BPH, FH) in the age-adjusted geometric mean PSA level. In the multivariate model, BMI was associated with a non-significant decrease in geometric mean PSA (p-trend = 0.06). A significant increase in geometric mean PSA was observed for both BPH ((ratio of geometric means (RGM) = 1.42, 95% CI 1.21 ″C 1.66) and a FH of PCa (RGM = 1.22, 95% CI 1.00 ″C 1.48). Current use of statins was associated with a 19% reduction in the geometric mean PSA (RGM = 0.81, 95% CI 0.70 ″C 0.95). CONCLUSIONS A number of factors independently altered the geometric mean PSA levels in men without a history of PCa. Statin use was independently associated with a 19% reduction in geometric mean PSA, while the effect of BMI on PSA was not significant when adjusting for confounders. Age, BPH and FH of PCa were associated with increased PSA levels. These results should help in interpreting PSA values in men undergoing screening for PCa. Seattle, WA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e800 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan L. Wright More articles by this author Daniel W. Lin More articles by this author Janet L. Stanford More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL(-1). The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose x fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Sensitivity and specificity of a whole-blood RNA transcript-based diagnostic test for the diagnosis of prostate cancer (CaP) compared with prostate-specific antigen (PSA) alone

5052 Background: Screening for CaP with PSA testing is limited by a high number of false postives, particularly in the setting of benign prostatic hypertrophy (BPH). The goal of this study was to develop whole blood RNA transcript-based diagnostic tests that improve the diagnosis of CaP over PSA alone. Methods: From August 2006 to October 2008, three prospective cohorts of men consented to the collection of whole blood in PAXgene Blood RNA tubes for gene expression analysis: men with newly diagnosed, localized, untreated CaP, otherwise healthy men without CaP, and otherwise healthy men with BPH. 168 inflammation and CaP-related genes (Source MDx Precision Profiles) were assayed using optimized Q-PCR technology. Logistic regression methods were used to develop models to optimize prostate cancer diagnosis. Results: 182 men underwent expression analysis (n = 76, 76 and 30 for CaP, normal, and BPH cohorts, respectively). The CaP and normal cohorts were age matched (median age 60 yrs); the BPH cohort median age was 70. Considering only the CaP and normal cohorts, PSA alone (using a cut-off of 4 ng/ml) had a specificity of 94.7%, but sensitivity of only 71.1% for diagnosis of CaP, or 90.8% and 77.6%, respectively, when using age-adjusted PSA criteria. A model consisting of the expression analysis of 6 genes and PSA had a higher specificity (96.1%) and a much improved sensitivity (97.4%) for CaP diagnosis. When the BPH cohort was added, the improvement of the 6-gene model remained (sensitivity and specificity of 97.4% and 92.0% vs 77.6% and 88.1% using the age-adjusted PSA criteria). Further model development using the CaP and BPH cohorts yielded a 5-gene model which, integrated with PSA and age, correctly predicted 96.1% of the CaP pts and 93.3% of BPH pts. Conclusions: These results suggest that specific whole blood RNA transcript levels can assess abnormal gene expression associated with CaP. Such a molecular CaP biomarker would be a powerful tool to reduce unnecessary biopsies in patients without CaP and detect CaP in patients with PSA values below the current cutoff. Validation of these results is ongoing and will be available at the time of the meeting. [Table: see text]

Do Changes in a High Serum Prostate-Specific Antigen Level and the Free/Total Prostate-Specific Antigen Ratio after Antibiotic Treatment Rule Out Biopsy and the Suspicion of Cancer?

Objectives: To evaluate the impact of antibiotic treatment in patients with higher-than-normal prostate-specific antigen (PSA) levels in terms of changes both in total PSA and free/total (f/t) PSA ratios. Materials and Methods: Serum PSA and f/t PSA changes after antibiotic treatment in 85 patients with normal digital rectal examination but elevated age-adjusted serum PSA levels were evaluated with relevance to biopsy results. Results: Serum PSA levels decreased after antibiotic treatment in 47 of 85 patients. The f/t PSA ratio decreased or remained unchanged in 21 and increased in 26 of these 47 cases. Cancer detection rate in the former group was 52.4% (11/21), while it was 7.7% (2/26) in the latter (p = 0.002). There were 38 patients with increased PSA levels after antibiotics. The f/t PSA ratios decreased or remained unchanged in 20 and increased in 18 of these 38 cases. Cancer detection rates were 55% (11/20) in the former and 16.7% (3/18) in the latter group (p = 0.003). Conclusions: The PSA and f/t PSA levels may change with long-term antibiotic treatment in patients with elevated PSA values. The f/t PSA ratio rather than total PSA appears to be more helpful in suggesting prostate cancer in these cases.

Effect of ageing and body mass index on prostate-specific antigen levels among Chinese men in Singapore from a community-based study

OBJECTIVE To assess the effect of ageing and body mass index (BMI) on prostate-specific antigen (PSA) among Chinese men from the results of the 2005 Prostate Awareness Week in Singapore. SUBJECTS AND METHODS In all, 2714 men participated in the programme, consisting of 2431 Chinese, 114 Malays, 117 Indians and 52 'others'. Of these, 2410 Chinese men who had a PSA level of <20 ng/mL and were aged >50 years but <80 years were included in the analysis. Height and weight were used to calculate the BMI. The relationship between age and PSA levels was analysed using linear regression and bivariate correlation, and the associations among different groups of BMI and PSA levels were analysed using analysis of variance and covariance. RESULTS PSA levels were significantly correlated with age (correlation coefficient, r = 0.27, P < 0.001). Analyses showed a significant inverse association between PSA level and BMI; mean PSA levels decreased with increasing BMI for both standards (standard classification; geometric mean, GM, PSA of 1.08, 1.06, 0.96, 0.83 ng/mL for a BMI of <18.5, 18.5-24.9, 25-29.9 and > or =30 kg/m(2), respectively, P trend <0.01; and for Asian classification, GM PSA 1.08, 1.09, 0.96, 0.91 ng/mL for a BMI of <18.5, 18.5-22.9, 23-27.5 and > or =27.5, respectively, P trend <0.001). There were significant differences (P < 0.05) in the age-adjusted GM PSA levels for the groups with BMI <25 (1.05 ng/mL) and BMI > or =25 kg/m(2) (0.97 ng/mL). Similarly, there were significant differences (P < 0.05) in the age-adjusted GM PSA levels in those with a BMI of <30 (1.03 ng/mL) and > or =30 kg/m(2) (0.85 ng/mL). CONCLUSION These data suggest that the BMI in Chinese men in Singapore is significantly associated with PSA levels, especially among the obese men aged 70-79 years.

Perception of Abnormal Serum Prostate-Specific Antigen (PSA) Test Results amongst Family Practitioners

With increased use of serum prostate-specific antigen (PSA) testing, prostate cancers are diagnosed at an earlier stage in younger men, when radical curative treatments are appropriate. Modifications of the PSA test such as PSA velocity and age-adjusted values are available to aid in the selection of patients for biopsy. However, it is not clear whether these data are used in general practice. A self-administered questionnaire was mailed to all primary care practices within one region in the UK. A series of visual analogue questions designed to identify referral thresholds for age-adjusted PSA levels and PSA velocity were used to identify patterns in referral behaviour. Individual family practitioners see only small numbers of patients requesting PSA tests or with newly diagnosed prostate cancer each year. The median (range) thresholds considered for referral at ages 45, 55, 65, 75 and 85 years were 4.5 ng/ml (2.5-15.5 ng/ml), 5.5 ng/ml (3.0-15.5 ng/ml), 6.5 ng/ml (3.5-15.5 ng/ml), 6.5 ng/ml (3.5-25.5 ng/ml), and 7.5 ng/ml (3.5-25.5 ng/ml), respectively. Only 5% of practitioners correctly identified the age-specific PSA threshold for referral of a 45-year-old man. It is important to remember that younger men (even those in their forties and fifties) may be at risk of prostate cancer even if asymptomatic. It is important in a climate of increasing demand for PSA testing that those who initiate the process understand the implications and limitations of testing, including appropriate triggers for referral to secondary care. The exact approach required for the successful dissemination of this information to primary care is not clear, but our data suggest that a better understanding is required.

Age Adjusted Prostate Specific Antigen and Prostate Specific Antigen Velocity Cut Points in Prostate Cancer Screening

We identified age adjusted prostate specific antigen and prostate specific antigen velocity cut points for prostate cancer biopsy. A cohort of 33,643 men was retrieved from the Duke Prostate Center database. Of this group 11,861 men with 2 or more prostate specific antigen values within 2 years were analyzed for age adjusted prostate specific antigen and prostate specific antigen velocity performance in cancer risk assessment using a receiver operating characteristic curve. In the 11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate cancer groups median prostate specific antigen and prostate specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the cancer detection rate but decreased the positive predictive value. Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate specific antigen velocity cut points should be age adjusted. In men 50 to 59 years old prostate specific antigen and prostate specific antigen velocity cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively. Factors of age, sensitivity, specificity, positive predictive value and cancer prevalence are critical for obtaining the desired balance between cancer detection and negative biopsy.