Prostate-specific Antigen Testing For Prostate Cancer Research Articles

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. isrctn.org Identifier: ISRCTN92187251.

Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

BackgroundScreening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers.MethodsThe Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50–69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation.ResultsIn the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million.ConclusionsIntroducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.

Predictors of Low-Value PSA Screening in Elderly Men

<h3>Purpose/Objective(s)</h3> The US Preventive Services Task Force (USPSTF) advises against prostate-specific antigen (PSA) testing for prostate cancer in men over 70 and identifies men aged 55 - 69 as the target screening group. The PSA test for prostate cancer is limited by its high false-positive rate and often leads to overdiagnosis of prostate cancer. Together, these can expose patients to anxiety, invasive biopsies, and possible over-treatment. We evaluate the predictors of recent PSA testing in men over 70 using Behavioral Risk Factor Surveillance System (BRFSS) survey data. <h3>Materials/Methods</h3> BRFSS 2020 data from PSA-related questions were analyzed, including time since last PSA test, PSA test reason, and whether a provider discussed the advantages and disadvantages of PSA screening with respondents. Men over 70 who answered PSA-related questions met our study criteria. We defined "recent testing" as having had a PSA test within the past two years. We used weighted multivariable logistic regressions with two-sided significance tests to measure effects of age, insurance status, having a primary care physician (PCP), and having discussion of PSA test risks and benefits with a provider on recent testing. Recent testing rates and percentages of men tested via routine screening vs. prostate-specific evaluations were calculated. <h3>Results</h3> Our cohort included 33,556 men. Recent PSA testing was high in men over 70. Men aged 70-75, 75-80, 80+ had testing rates of 56.3%, 53.4%, and 40.8% respectively. In a multivariable regression model, positive predictors of recent testing in men over 70 included being insured (OR = 1.202, 95% CI 1.195 - 1.21, p < 0.001), having a PCP (OR = 1.459, 95% CI 1.454 - 1.465, p < 0.001), and discussing the advantages of PSA testing with a PCP (OR = 3.507, 95% CI 3.5 - 3.515, p < 0.001). Discussing the disadvantages of PSA testing with a PCP had only a small, negative effect on recent testing in men over 70 (OR = 0.996, 95% CI 0.995 - 0.998, p < 0.001). Among men over 70 who had recent PSA tests, 73.3% reported routine testing as the main reason for their tests. We repeated our analysis with the unweighted survey data and found no significant changes in results. <h3>Conclusion</h3> Despite USPSTF guidelines, men over 70 continue to be screened with PSA at a high rate. Routine testing accounted for the majority of recent PSA tests in men over 70. Having a discussion of the benefits of PSA tests with a provider had the largest effect on recent testing in men over 70, which underscores the role of the provider in positively influencing PSA testing rates. Other related predictors of PSA testing in men over 70 included being insured and having a PCP. These findings suggest changes can be made at the provider-level to increase adherence to guidelines on age-based PSA testing.

Prostate-specific antigen testing and opportunistic prostate cancer screening: a cohort study in England, 1998-2017.

BackgroundProstate cancer is a leading cause of cancer- related death. Interpreting the results from trials of screening with prostate-specific antigen (PSA) is complex in terms of defining optimal prostate cancer screening policy.AimTo assess the rates of, and factors associated with, the uptake of PSA testing and opportunistic screening (that is, a PSA test in the absence of any symptoms) in England between 1998 and 2017, and to estimate the likely rates of pre-randomisation screening and contamination (that is, unscheduled screening in the ‘control’ arm) of the UK-based Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP).Design and settingOpen cohort study of men in England aged 40–75 years at cohort entry (1998–2017), undertaken using the QResearch database.MethodEligible men were followed for up to 19 years. Rates of PSA testing and opportunistic PSA screening were calculated; Cox regression was used to estimate associations.ResultsThe cohort comprised 2 808 477 men, of whom 631 426 had a total of 1 720 855 PSA tests. The authors identified that 410 724 men had opportunistic PSA screening. Cumulative proportions of uptake of opportunistic screening in the cohort were 9.96% at 5 years’, 22.71% at 10 years’, and 44.13% at 19 years’ follow-up. The potential rate of contamination in the CAP control arm was estimated at 24.50%.ConclusionA substantial number of men in England opt in to opportunistic prostate cancer screening, despite uncertainty regarding its efficacy and harms. The rate of opportunistic prostate cancer screening in the population is likely to have contaminated the CAP trial, making it difficult to interpret the results.

The role of modelling in the policy decision making process for cancer screening: example of prostate specific antigen screening.

Although randomised controlled trials are the preferred basis for policy decisions on cancer screening, it remains difficult to assess all downstream effects of screening, particularly when screening options other than those in the specific trial design are being considered. Simulation models of the natural history of disease can play a role in quantifying harms and benefits of cancer screening scenarios. Recently, the US Preventive Services Task Force issued a C-recommendation on screening for prostate cancer for men aged 55-69 years, implying at least moderate certainty that the benefit is small. However, modelling based on data from the European Randomized study of Screening for Prostate Cancer, which included quality-of-life estimates, showed that the ratio between benefits and harms is better, and likely to be reasonable, for men screened between the ages of 55 and 63 years (i.e. by using an earlier stopping age than applied in the trial setting). This commentary article considers the importance of simulation modelling in the decision-making process for (prostate) cancer screening. The paper also explores whether the recently published Cluster Randomized Trial of PSA Testing for Prostate Cancer, a trial of a single prostate specific antigen (PSA) testing intervention in the UK, changes the evidence for regular PSA testing for men aged 55-63 years by replicating the trial using a simulation model.

Beyond PSA testing for prostate cancer.

Prostate cancer is now the most common cancer diagnosed in men in Australia,1 and Australia has one of the highest incidence rates of prostate cancer in the world, with an estimated age-standardised rate of 119.2 per 100 000 men.2 Before 1960, the primary diagnostic test for prostate cancer was the prostatic acid phosphatase test. This was eventually replaced in the 1980s by the prostate-specific antigen (PSA) test.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. ISRCTN Identifier: ISRCTN92187251.

Cross-sectional study evaluating data quality of the National Cancer Registration and Analysis Service (NCRAS) prostate cancer registry data using the Cluster randomised trial of PSA testing for Prostate cancer (CAP)

ObjectivesTo compare the completeness and agreement of prostate cancer data recorded by the National Cancer Registration and Analysis Service (NCRAS) with research-level data specifically abstracted from medical records from the...

Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial.

BackgroundSociodemographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for prostate-specific antigen (PSA) testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).MethodsAge, rurality and deprivation among 197,763 men from 271 cluster-randomised primary care centres in the UK were compared between those responding (n = 90,300) and those not responding (n = 100,953) to a prostate cancer testing invitation.ResultsThere was little difference in age between responders and nonresponders. Responders were slightly more likely to come from urban rather than rural areas and were slightly less deprived than those who did not respond.ConclusionThese data indicate similarities in age and only minor differences in deprivation and urban location between responders and nonresponders. These differences were smaller, but in the same direction as those observed in other screening trials.Trial registration ISRCTN92187251. Registered on 29 November 2004.

Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

ObjectivesTo evaluate the accuracy of routine data for costing inpatient resource use in a large clinical trial and to investigate costing methodologies.DesignFinal-year inpatient cost profiles were derived using (1) data...

Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer).

BackgroundIn cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers’ ability to correctly guess the trial arm.MethodsOver 550 General Practitioner (GP) practices (>415,000 men aged 50–69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm.Results1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation.ConclusionsIt is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them.Trial registrationISRCTN92187251Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2288-15-6) contains supplementary material, which is available to authorized users.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

Background:Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing.Methods:Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50–69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up.Results:Among randomised practices, 271 (68%) in the intervention arm (198 114 men) and 302 (78%) in the control arm (221 929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices).Conclusions:The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

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.

Use of Cancer-Screening Services Among Persons With Serious Mental Illness in Sacramento County

This study examined the use of breast, cervical, colorectal, and prostate cancer-screening services by persons with serious mental illness enrolled in the Sacramento County Mental Health clinics. Of 387 outpatients approached from January 2005 to May 2007, 229 were interviewed. Whereas 97% of the women had received cervical cancer screening at least once in their lifetime, more than 50% of eligible persons over age 50 had never received colorectal cancer screening. Recent use of screening services was highest for cervical cancer (69% had had a Pap test in the past three years) and lowest for colorectal cancer (12% had had a fecal occult blood stool test in the past year or a flexible sigmoidoscopy or colonoscopy in the past five years). Among persons with serious mental illness, lifetime screening of cervical cancer was higher than for breast, prostate, and colorectal cancers. Receipt of routine, timely cancer screening was low, especially for colorectal cancer.

PSA testing for prostate cancer: an online survey of the views and reported practice of General Practitioners in the UK

BackgroundThe role of Prostate Specific Antigen (PSA) testing in the early detection of prostate cancer is controversial. Current UK policy stipulates that any man who wishes to have a PSA test should have access to the test, provided he has been given full information about the benefits and limitations of testing. This study aimed to determine UK GPs' current reported practice regarding PSA testing, and their views towards informed decision-making and PSA testing.MethodOnline questionnaire survey, with a sample of 421 GPs randomly selected from a database of GPs across the UK.Results95% (400/421) of GPs responded. 76% of GPs reported having performed a PSA test for an asymptomatic man at least once in the previous three months, with 13% reported having tested more than five men in this period. A majority of GPs reported they would do a PSA test for men presenting with a family history and requesting a test, for asymptomatic men requesting a test and also for men presenting with lower urinary tract symptoms. Reported testing rates were highest for men with a family history. Amongst men with lower urinary tract symptoms and men with no symptoms, reported testing rates were significantly higher for older than younger men.The majority of GPs expressed support for the current policy (67%), and favoured both the general practitioner and the man being involved in the decision making process (83%). 90% of GPs indicated that they would discuss the benefits and limitation of testing with the man, with most (61%) preferring to ask the man to make a further appointment if he decides to be tested.ConclusionThis study indicates that PSA testing in asymptomatic men is a regular occurrence in the UK, and that there is general support from GPs for the current policy of making PSA tests available to 'informed' men who are concerned about prostate cancer. While most GPs indicated they would discuss the benefits and limitations prior to PSA testing, and most GPs favoured a shared approach to decision making, it is not known to what extent men are actually being informed. Research is needed to evaluate the most effective approach to assisting men in making an informed decision about whether or not to have a PSA test.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Clinical stage T1c prostate cancer: Pathologic outcomes following radical prostatectomy in black and white men

BACKGROUND The incidence of prostate cancer in black men is 50% to 70% higher than among age-matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate-specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer. METHODS We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins. RESULTS Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P = 0.02). CONCLUSIONS Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early-detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high-risk group. Prostate 50: 236–240, 2002. © 2002 Wiley-Liss, Inc.

Clinical utility of measurements of free and total prostate-specific antigen (PSA): a review.

Prostate-specific antigen (PSA) is a widely-used tumor marker to aid in the early detection of prostate cancer. PSA testing has appreciable false-positive and false-negative results, particularly in the 2.5-10.0 ng/ml range. Measurements of the percentage of nonprotein-bound (free) PSA in serum, which is lower in patients with prostate cancer, has been evaluated as a method for increasing the accuracy of PSA testing. The literature on forms of PSA in serum, as it relates to issues of clinical utility for prostate cancer screening, was reviewed and summarized through May 1996. Measurements of the percentage of free PSA in serum increase the accuracy of PSA testing for prostate cancer in men whose total PSA levels are 2.5-10.0 ng/ml. Cutoffs for screening are affected by prostate volume and total PSA levels. One study also demonstrated a correlation between percentage of free PSA and pathologic features of cancer aggressiveness. Measurement of free PSA in serum has potential clinical utility for increasing the sensitivity and specificity of PSA screening. Insufficient data are available to establish cutoffs to be used in clinical practice. Cutoffs are affected by total PSA level and prostate volume. The prevalence rate of cancer in the screened population (age, race, previous biopsy history, etc.) will also influence screening cutoffs. Percentage of free PSA may also correlate with the potential aggressiveness of early-stage prostate cancer.