Routine Prostate-specific Antigen Screening Research Articles

Fasting times in serum PSA assay.

Prostate-specific antigen (PSA) test for prostate cancer is the only serum-based cancer screening test that is widely accepted. A large number of PSA tests are done in developed countries such as the United States due to the recommendation that men be screened annually starting at age 50. With the rapid economic development and increased access to healthcare, countries like China have also experienced a dramatic increase in the utilization of PSA test. This trend is unlikely to change significantly despite the recent recommendation against routine PSA screening by the US Preventive Health Task force. As a screening test, PSA's normal upper limit is set at 4 ng ml−1 by most physicians, although some prefer to use 2.5 ng ml−1 as the cutoff value. Men with increased PSA levels are usually referred for prostate biopsy by an urologist to rule out prostate cancer. For this reason, accurate PSA testing is important. Although many preanalytic and analytic variables can influence the test results, an important variable that can be controlled is the fasting time before the blood draw. Because older men often have concerns of other health issues, it may be assumed that most routine PSA tests may be performed along with other lab tests such as lipid panel or metabolic panel. As a result, many men will fast before the PSA test, although how fasting affects PSA measurement was unclear. A previous study by Tuncel et al.1 examined the effects of fasting times in a group of 80 men, but the fasting times did not exceed 8 h and the sample size was relatively small. Another important utility of PSA test is to monitor disease recurrence after surgery, radiation therapy or hormonal therapy for the treatment of prostate cancer. In this setting, it is the trend over time that gives indications of disease remission vs recurrence. As a result, it is very important to eliminate preanalytic variables that may affect the measurement, since an increase in PSA level causes concern for disease recurrence and may prompt clinical intervention. Fasting time is an important variable here if it affects the results. In the article “Fasting time and serum PSA levels”, published in Asian Journal of Andrology, Lau et al.2 investigated the effects of fasting times on the measured PSA levels in a very large community-based cohort of 157 276 men. The average fasting time was 12.7 h with a minimum, and maximum fasting time of 1 and 16 h, respectively. Age-specific reference ranges for Caucasian males were used, although race was not taken into consideration in the study. The authors developed a dynamic mathematical model to calculate the percentage of individuals expected to experience a change in PSA diagnostic interpretation (e.g. normal vs abnormal result) based on variations in fasting time. The results indicate that fasting time has a statistically significant effect on serum PSA levels, and an increased fasting time is generally associated with a modest increase in the number of patients with abnormal PSA values, particularly at the extremes. The peak PSA levels were observed at 4 h of fasting, which may be due to diurnal variation. Simulating the changes that would occur in PSA values if fasting times were altered revealed that the percentage change in the number of abnormal PSA values can range from −1.07% to 1.63%, which would translate into minimal clinical effect. The authors recommend that the optimal time to obtain an accurate PSA level is fasting for 7–9 h, which avoids the increased PSA levels observed with fasting extremes as well as possible diurnal rhythm variations that may exist in shorter fasting times. This is an interesting study with meaningful results. The authors have addressed obvious limitations such as potential recall errors by the patients and the nonrandomness of the cohorts. Based on these findings, it seems that fasting time may not be a concern for prostate cancer screening as the small variations (~1%) is unlikely to change the PSA value over or under the threshold for most patients. However, for patients monitored for disease recurrence such as those after surgery or radiation for high risk prostate cancer, or for patients with advanced prostate cancer treated with conventional hormonal therapy or the newer agents, testing PSA under similar fasting conditions (7–9 h) may be advisable for consistent testing, since the trend in serial PSA tests are critical for clinical decision-making. ACKNOWLEDGMENTS The support provided by China Scholarship Council (CSC) to Xiang Xu is acknowledged.

PSA testing without clinical indication for prostate cancer in relation to socio-demographic and clinical characteristics in the Danish Diet, Cancer and Health Study

Background. Social differences in prostate cancer (PC) incidence and mortality might be related to testing for prostate-specific antigen (PSA). Although routine PSA screening is not recommended in Denmark, testing without clinical indication increased during the past decade. We evaluated associations between socio-demographic or clinical characteristics and PSA testing without clinical indication. Material and methods. In the Danish Diet, Cancer and Health Cohort, we identified 1051 men with PC diagnosed in 1993–2008. Diagnostic and clinical characteristics were obtained from medical records, and socio-demographic information was retrieved from administrative registers. We used general logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between socio-demographic or clinical characteristics and PSA testing without clinical indication. Cox regression analysis was used to examine associations with mortality. Results. PSA testing without clinical indication was less likely among patients > 67 years (OR 0.7; 0.5–1.0). Men who were, PSA tested without clinical indication, were more likely to have vocational training (OR 1.8; 1.1–2.9) or higher education (OR 1.5; 0.9–2.5) and less likely to have advanced disease (OR 0.6; 0.4–0.9). PSA testing without clinical indication more often preceded therapy with curative intent (OR 1.8; 1.1–2.9) and less often palliative treatment (OR 0.6; 0.3–1.0). Men who were PSA tested without clinical indication had non-significantly lower overall and PC-specific mortality [hazard ratios 0.8 (0.5–1.2) and 0.6 (0.3–1.1), respectively]. Conclusions. PSA testing without clinical indication was associated with higher educational level. PC detected by PSA testing with no clinical indication was more often localized and treated with curative intent.

Recommendations by Canadian urologists and radiation oncologists for the treatment of clinically localized prostate cancer

Previous work has shown that urologists and radiation oncologists prefer the treatment that they themselves deliver when treating clinically localized prostate cancer. Our objective was to determine whether Canadian radiation oncologists and urologists have similar biases in favour of the treatments that they themselves deliver for localized prostate cancer. We developed a survey to poll the beliefs that Canadian radiation oncologists and urologists held toward prostate specific antigen (PSA) screening, survival benefits of treatment, recommendations for treatment of prostate cancer and the likelihood of side effects with each therapy. Urologists were more likely to recommend routine PSA screening for men up to age 70 (p < 0.001), while radiation oncologists were more likely to recommend PSA screening for men over age 80 (p < 0.04). More urologists felt that there was "definitely" a survival advantage with radical prostatectomy (RP) (60% v. 21%, p < 0.001). More radiation oncologists recommend external beam radiation therapy (EBRT) (p < 0.01) or brachytherapy (p < 0.03) to treat low-risk prostate cancer. More urologists than radiation oncologists recommend RP for intermediate-risk patients (98% v. 70%, p < 0.001). Most Canadian urologists and radiation oncologists recommend routine PSA screening for men aged 50 to 70. A significant preference was detected among both urologists and radiation oncologists for the treatment that they themselves deliver. While both urologists and radiation oncologists recommend prostatectomy for the treatment of low-risk localized prostate cancer, urologists are significantly less likely to recommend EBRT. Conversely, when patients present with intermediate-risk prostate cancer, radiation oncologists were significantly less likely than urologists to recommend a prostatectomy.

Prostate cancer: Interventions aimed at improving morbidity, mortality

In recent months, FDA approved Xtandi (enzalutamide—Astellas, Medivation), a new agent for metastatic castration-resistant prostate cancer, and expanded the approval of Zytiga (abiraterone—Janssen), an existing agent for the same patient population. In addition, recently published trials have shown the clinical activity of Cometriq (cabozantinib— Exelixis) for patients with advanced prostate cancer and bone metastases, as well as the benefi ts of aspirin therapy in reducing the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy.

Primary care providers' perspectives on discontinuing prostate cancer screening

Clinical guidelines recommend against routine prostate-specific antigen (PSA) screening for older men and for those with lower life expectancies. The authors of this report examined providers' decision-making regarding discontinuing PSA screening. A survey of primary providers from a large, university-affiliated primary care practice was administered. Providers were asked about their current screening practices, factors that influenced their decision to discontinue screening, and barriers to discontinuing screening. Bivariate and multivariable logistic regression analyses were used to examine whether taking age and/or life expectancy into account and barriers to discontinuing were associated with clinician characteristics and practice styles. One hundred twenty-five of 141 providers (88.7%) participated in the survey. Over half (59.3%) took both age and life expectancy into account, whereas 12.2% did not consider either in their decisions to discontinue PSA screening. Providers varied in the age at which they typically stopped screening patients, and the majority (66.4%) reported difficulty in assessing life expectancy. Taking patient age and life expectancy into account was not associated with provider characteristics or practice styles. The most frequently cited barriers to discontinuing PSA screening were patient expectation (74.4%) and time constraints (66.4%). Black providers were significantly less likely than nonblack providers to endorse barriers related to time constraints and clinical uncertainty, although these results were limited by the small sample size of black providers. Although age and life expectancy often figured prominently in decisions to use screening, providers faced multiple barriers to discontinuing routine PSA screening.

Body Composition, Abdominal Fat Distribution, and Prostate-Specific Antigen Test Results

There are competing theories explaining the observed inverse association between obesity and screening prostate-specific antigen (PSA) levels: (a) endocrine disturbances related to abdominal obesity influence PSA production and (b) increased plasma volume associated with obesity dilutes PSA. Under the endocrine disturbance hypothesis, fat mass, but not lean mass, and an abdominal distribution of fat are expected to be inversely associated with PSA levels. Under plasma volume dilution theory, PSA levels are inversely associated with both lean and fat mass and are independent of body fat distribution patterns. Data on weight, percent body fat measured by bioimpedance, and waist circumference from approximately 8,000 men undergoing routine PSA screening were evaluated. Multivariate linear regression analyses controlling for age and race/ethnicity were used to determine whether fat, lean mass, or waist circumference were associated with PSA. PSA levels were significantly inversely associated with both lean and fat mass. In separate models, a 5-pound difference in lean mass and fat mass was associated, respectively with a -0.9% (P < 0.001) and -0.7% (P = 0.001) difference in PSA test results. In a model that simultaneously considered lean and fat mass, a 5-pound difference in lean mass and fat mass was associated, respectively, with a -0.6% (P = 0.03) and -0.4% (P = 0.08) difference in PSA test results. Controlling for body mass index, a 1-inch difference in waist circumference was associated with a +0.9% (P = 0.01) difference in PSA levels. The results are more consistent with predictions arising from the volume dilution theory than the hormone disturbance theory.

Reactions of Potential Jurors to a Hypothetical Malpractice Suit Alleging Failure to Perform a Prostate-Specific Antigen Test

We conducted focus groups with 47 potential jurors who were presented with different scenarios in a hypothetical malpractice case involving failure to order a PSA test. Better documentation that a patient made an informed decision to decline a PSA test appeared to provide more medical-legal protection for physicians, especially with the use of a decision aid.

Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated with increased prostate cancer incidence

Recurrent or persistent inflammation has emerged as an important factor in cancer development. Overexpression of macrophage migration inhibitory factor (MIF), an upstream regulator of innate immunity with pleiotropic effects on cell proliferation, has been implicated in prostate cancer (CaP). Two polymorphisms in the promoter of the MIF gene (-173G to C transition and seven copies of the -794 CATT repeat) are associated with increased MIF expression in vivo and poor prognosis in autoimmune diseases. We conducted a retrospective analysis of 131 CaP patients and 128 controls from a group of Veterans' Administration patients undergoing routine prostate-specific antigen screening. Patients with CaP were enrolled regardless of treatment. Inclusion criteria for the control group were absence of documented diagnosis of cancer and/or chronic inflammation within patient computerized records. Logistic regression demonstrated a significant association between CaP and the -173G/C, the -173C/C and the -794 7-CATT MIF polymorphisms (P<0.001). Patients with the -794 7-CATT allele had an increased risk of CaP recurrence at 5 years. Individuals with -173G/C, -173C/C and -794 7-CATT MIF genotypes have an increased incidence of CaP and these genotypes may serve as an independent marker for cancer recurrence.

Selections from current literature: PSA screening for prostate cancer.

Prostate cancer has been the focus of several recent reports in the US news media.Additional attention has been focused on this issue due to the disclosure by several prominent US individuals that they have or have had prostate cancer. These include US presidential candidate, Senator Robert Dole, Gulf War hero, retired General Norman Schwarzkopf and the billionaire financier Michael Milken. Such specific cases highlight the fact that prostate cancer—'the man's cancer'—has risen sharply both in incidence and prevalence over the last few years. In men, prostate cancer is the most common type of cancer in the US and the second leading cause of cancer mortality. In 1996, it is estimated that there will be 317 100 new cases and 41 400 deaths as a result of prostate cancer in the US. The lifetime probability of a man developing prostate cancer is one in five. Currently the adjusted death rate from this disease among men living in industrialized countries of the world is greater than 15 per 100 000 population. What has caused this epidemic? A partial answer is the use of prostate specific antigen (PSA) as a screening test which has led to the diagnosis of many cancers that would have otherwise have remained undiagnosed, and never become clinically significant. This then leads to the question now being debated in the literature, fuelled by contradictory guidelines from several highly respected agencies: to screen or not to screen with PSA? The American Cancer Society (ACS) and the American Urological Association (AUA) currently recommend annual PSA testing for all men aged 50 years and older. The American Academy of Family Physicians (AAFP), Canadian Task Force on the Periodic Health Examination (CTF) and National Cancer Institute (NCI) all recommend against routine PSA screening in asymptomatic men. Furthermore, the recently published guidelines by the United States Preventive Services Task Force (USPSTF) also recommend against routine PSA screening.