Prostate-specific Antigen Test Results Research Articles

Urinary fatty acid biomarkers for prostate cancer detection.

The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60-75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients' PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67-0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46-0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis.

Real-world comparison of prostate-specific antigen (PSA) response in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or enzalutamide (ENZ).

51 Background: APA and ENZ, two androgen receptor synthesis inhibitors (ARSIs), used in combination with androgen deprivation therapy (ADT) are among the recommended treatments for patients with mCSPC. Deep PSA response, evaluated as ≥90% PSA decline (PSA90), is an important outcome after ARSI initiation, with early, deep response associated with longer survival. The primary objective of this study was to compare PSA90 response in ARSI-naïve patients with mCSPC by 6 months after initiating APA or ENZ in real-world clinical practice. Methods: Linked electronic medical record (EMR) data of US community urology practices in the from PPS Analytics and administrative health data from Komodo Health Solutions Research Database were evaluated. Patients with mCSPC were selected into two cohorts, based on the index date, defined as the first paid pharmacy claim or in-office dispensation for APA or ENZ on or after 16 Dec 2019. Patients were required to have ≥12 months of pre-index EMR clinical activity. Pre-index characteristics (i.e., age, race, geographic region, payer type, index year, time from metastasis, time from first prostate cancer [PC] diagnosis, de novo PC, ADT use, first-generation antiandrogen use, chemotherapy use, metastasis locations, most recent PSA level, testosterone level, and Gleason score) were balanced between cohorts with inverse-probability treatment weighting (IPTW). Patients were followed from index date until the earliest of index ARSI discontinuation or switch, radiopharmaceutical initiation, end of open administrative claim or EMR clinical activity, or end of data availability (30 Sep 2022). PSA90 was defined as the earliest ≥90% decline in PSA relative to most recent pre-index PSA. The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: In total 860 APA and 869 ENZ patients were identified. Patient pre-index characteristics were balanced with IPTW (Table). By 6 months post-index, 80.3% of APA and 75.0% of ENZ patients had ≥1 PSA test result. By 6 months, significantly more APA patients attained a PSA90 response, as compared to ENZ patients (p=0.005; Table). The median time to PSA90 response was 3.5 months for APA and 4.9 months for ENZ. Conclusions: This US real-world study of patients with mCSPC demonstrated that treatment with APA produces a deep, early PSA response by 6 months in a greater percentage of patients than treatment with ENZ. [Table: see text]

Cost-Effectiveness of Annual Prostate MRI and Potential MRI-Guided Biopsy After Prostate-Specific Antigen Test Results

Magnetic resonance imaging (MRI) and potential MRI-guided biopsy enable enhanced identification of clinically significant prostate cancer. Despite proven efficacy, MRI and potential MRI-guided biopsy remain costly, and there is limited evidence regarding the cost-effectiveness of this approach in general and for different prostate-specific antigen (PSA) strata. To examine the cost-effectiveness of integrating annual MRI and potential MRI-guided biopsy as part of clinical decision-making for men after being screened for prostate cancer compared with standard biopsy. Using a decision analytic Markov cohort model, an economic evaluation was conducted projecting outcomes over 10 years for a hypothetical cohort of 65-year-old men in the US with 4 different PSA strata (<2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, >10 ng/mL) identified by screening through Monte Carlo microsimulation with 10 000 trials. Model inputs for probabilities, costs in 2020 US dollars, and quality-adjusted life-years (QALYs) were from the literature and expert consultation. The model was specifically designed to reflect the US health care system, adopting a federal payer perspective (ie, Medicare). Magnetic resonance imaging with potential MRI-guided biopsy and standard biopsy. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold of $100 000 per QALY was estimated. One-way and probabilistic sensitivity analyses were performed. For the 3 PSA strata of 2.5 ng/mL or greater, the MRI and potential MRI-guided biopsy strategy was cost-effective compared with standard biopsy (PSA 2.5-4.0 ng/mL: base-case ICER, $21 131/QALY; PSA 4.1-10.0 ng/mL: base-case ICER, $12 336/QALY; PSA >10.0 ng/mL: base-case ICER, $6000/QALY). Results varied depending on the diagnostic accuracy of MRI and potential MRI-guided biopsy. Results of probabilistic sensitivity analyses showed that the MRI and potential MRI-guided biopsy strategy was cost-effective at the willingness-to-pay threshold of $100 000 per QALY in a range between 76% and 81% of simulations for each of the 3 PSA strata of 2.5 ng/mL or more. This economic evaluation of a hypothetical cohort suggests that an annual MRI and potential MRI-guided biopsy was a cost-effective option from a US federal payer perspective compared with standard biopsy for newly eligible male Medicare beneficiaries with a serum PSA level of 2.5 ng/mL or more.

Development and Validation of a Tool to Identify Patients Diagnosed With Castration-Resistant Prostate Cancer.

Several novel therapies for castration-resistant prostate cancer (CRPC) have been approved with randomized phase III studies with continuing observational research either planned or ongoing. Accurately identifying patients with CRPC in electronic health care data is critical for quality observational research, resource allocation, and quality improvement. Previous work in this area has relied on either structured laboratory results and medication data or natural language processing (NLP) methods. However, a computable phenotype using both structured data and NLP identifies these patients with more accuracy. The Corporate Data Warehouse (CDW) of the Veterans Health Administration (VHA) was used to collect PCa diagnoses, prostate-specific antigen test results, and information regarding patient characteristics and medication use. The final system used for validation and subsequent analysis combined the NLP system and an algorithm of structured laboratory and medication data to identify patients as being diagnosed with CRPC. Patients with both a documented diagnosis of CRPC and a documented diagnosis of metastatic PCa were classified as having mCRPC by this system. Among 1.2 million veterans with PCa, the International Classification of Diseases (ICD)-10 diagnosis code for CRPC (Z19.2) identifies 3,791 patients from 2016 when the code was created until 2022, compared with the combined algorithm which identifies 14,103, 10,312 more than ICD-10 codes alone, from 2016 to 2022. The combined algorithm showed a sensitivity of 97.9% and a specificity of 99.2%. ICD-10 codes proved to be insufficient for capturing CRPC in the VHA CDW data. Using both structured and unstructured data identified more than double the number of patients compared with ICD-10 codes alone. Application of this combined approach drastically improved identification of real-world patients and enables high-quality observational research in mCRPC.

Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography

Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive. The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.

PCN254 CHARACTERISING INDIVIDUALS WITH NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER USING ROUTINE LINKED HEALTH DATASETS: A FEASIBILITY STUDY

Non-metastatic castration-resistant prostate cancer (nmCRPC) is a disease state in which cancer is localized but resistant to testosterone suppression therapy (Androgen Deprivation Therapy (ADT) or bilateral orchidectomy). There is relatively little real world data focusing on this disease state either for characterising patients or describing their treatment pathways. This study set out to assess the feasibility of using linked routine health datasets to identify individuals with nmCRPC and to estimate their nmCRPC progression date. The study datasets were routine health data for Wales hosted by the SAIL Databank, Swansea University, Wales. Records of patients diagnosed with prostate cancer between 2000 and 2015 were identified by clinical coding (ICD-10 and Read). An algorithm was designed to specify the features of nmCRPC based on presence of codes for testosterone suppression therapy, Prostate Specific Antigen (PSA) test results and codes indicating absence of metastatic disease. Only records that contained sufficient PSA test results to determine a rise during treatment (indicating progression to castration resistance) were included. The algorithm was tested with three different criteria for PSA test levels and intervals, and two thresholds of stringency for determining cases. The datasets produced a cohort of 38,021 individuals diagnosed with prostate cancer. Of these 14,860 received ADT while non-metastatic and 6,101 had at least three recorded PSA test results during ADT. The number of nmCRPC cases identified was between 1,281 and 1,534 (non-stringent criteria) and between 439 and 509 (stringent criteria). Case identification is dependent on accurate, complete coding. The results of this study suggest that it is feasible to use linked routine health datasets to create cohorts of individuals with nmCRPC, including an estimation of date of progression to nmCRPC. Various processes were investigated to improve data quality, particularly in the identification of metastases, resulting in cohorts of sufficient size to enable statistical analysis.

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.

Serial Percent Free Prostate Specific Antigen in Combination with Prostate Specific Antigen for Population Based Early Detection of Prostate Cancer

We characterized the diagnostic properties of serial percent free prostate specific antigen in relation to prostate specific antigen in a multiethnic, multiracial cohort of healthy men. A total of 6,982 percent free prostate specific antigen and prostate specific antigen measurements were obtained from participants in a greater than 12-year Texas screening study comprising 1,625 men who never underwent biopsy, 497 who underwent 1 or more biopsies negative for prostate cancer and 61 diagnosed with prostate cancer. We evaluated the ROC AUC of percent free prostate specific antigen and the proportion of patients with fluctuating values across multiple visits determined according to 2 thresholds (less than 15% vs 25%). The proportion of cancer cases in which percent free prostate specific antigen indicated a positive test before prostate specific antigen greater than 4 ng/ml did and the number of negative biopsies that would have been spared by negative percent free prostate specific antigen test results were calculated. Percent free prostate specific antigen fluctuated around its threshold of less than 25% (less than 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, and with negative and positive biopsies, respectively. At the same thresholds, percent free prostate specific antigen tested positive earlier than prostate specific antigen in 71.4% and 34.2% of cancer cases, respectively. Among men with multiple negative biopsies and PSA greater than 4ng/ml, percent free PSA would have tested negative in 31.6% and 65.8%, respectively. Percent free prostate specific antigen should accompany prostate specific antigen testing to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation.

Predictive value of prostate specific antigen kinetics in prostate cancer diagnosis

Background and Aim: Current Australian draft clinical practice guidelines for prostate specific antigen (PSA) testing do not recommend PSA kinetics due to a lack of quality evidence. We investigated the relationship between PSA kinetics and a subsequent diagnosis of prostate cancer. Method: A retrospective audit was conducted of prostate histopathology results from June 2015 with corresponding PSA test results. The laboratory receives both outpatient and hospital referrals. Inclusion criteria for analysis were the availability of ≥3 PSA results each spaced by ≥3 months for reliable calculation of PSA kinetic parameters (linear velocity, doubling time). Total PSA was measured on the Abbott Architect. Results: 512 patient records satisfied the criteria for analysis. PSA linear velocity >0.75 μg/L/year was associated with prostate cancer diagnosis [odds ratio (OR)=1.96, 95% confidence interval (CI)=1.22–3.18], which persisted in the cohort of men with any elevated PSA >3 μg/L (OR=1.80, 95%CI=1.10–2.97). PSA doubling time <3 years was not significantly associated with prostate cancer diagnosis (OR=1.17, 95%CI=0.93–2.17). Discussion: This retrospective analysis confirms the relationship between PSA velocity and prostate cancer, with potential utility of PSA velocity to stratify risk in men with an elevated PSA result.

Reducing the Harm of Prostate Cancer Screening: Repeated Prostate-Specific Antigen Testing

ObjectiveTo determine if repeating a prostate-specific antigen (PSA) test in men with an elevated PSA level is associated with a decreased risk of prostate biopsy and cancer diagnosis. Patients and MethodsA cohort of patients referred to the Ottawa Regional Prostate Cancer Assessment Clinic from April 1, 2008, through May 31, 2013, who had referral PSA levels between 4 and 10 ng/mL were included in the study. Univariate and multivariate associations between a normal result on repeated PSA testing and the risk of prostate biopsy, cancer diagnosis, and Gleason score of 7 or higher were examined. ResultsThe study cohort included 1268 patients. Repeated PSA test results were normal in 315 patients (24.8%). Men with normal results on repeated PSA testing were younger (mean ± SD age, 61.5±8.2 years vs 65.2±8.2 years; P<.001) and had lower referral PSA levels (mean ± SD, 5.5±1.4 ng/mL vs 6.6±1.5 ng/mL; P<.001) than men with an abnormal repeated PSA result. In multivariate analysis, men with normal results on repeated PSA testing were less likely to undergo prostate biopsy (relative risk [RR], 0.42; 95% CI, 0.34-0.50) and were at lower risk for cancer diagnosis (RR, 0.22; 95% CI, 0.14-0.34) and Gleason score of 7 or higher (RR, 0.16; 95% CI, 0.08-0.34) compared with men who had an abnormal repeated PSA test result. ConclusionRoutinely repeating a PSA test in patients with an elevated PSA level is independently associated with decreased risk of prostate biopsy and prostate cancer diagnosis. Men with an elevated PSA level should be given a repeated PSA test before proceeding to biopsy.

"What should happen before asymptomatic men decide whether or not to have a PSA test?" A report on three community juries.

To elicit the views of well informed community members on the ethical obligations of general practitioners regarding prostate-specific antigen (PSA) testing, and what should be required before a man undergoes a PSA test. Three community juries held at the University of Sydney over 6 months in 2014. Forty participants from New South Wales, of diverse social and cultural backgrounds and with no experience of prostate cancer, recruited through public advertising: two juries of mixed gender and ages; one all-male jury of PSA screening age. In contrast to Royal Australian College of General Practitioners guidelines, the three juries concluded that GPs should initiate discussions about PSA testing with asymptomatic men over 50 years of age. The mixed juries voted for GPs offering detailed information about all potential consequent benefits and harms before PSA testing, and favoured a cooling-off period before undertaking the test. The all-male jury recommended a staggered approach to providing information. They recommended that written information be available to those who wanted it, but eight of the 12 jurors thought that doctors should discuss the benefits and harms of biopsy and treatment only after a man had received an elevated PSA test result. Informed jury participants preferred that GPs actively supported individual men in making decisions about PSA testing, and that they allowed a cooling-off period before testing. However, men of screening age argued that uncertain and detailed information should be communicated only after receiving an elevated PSA test result.

Shifting paradigms in the estimation of survival for castration-resistant prostate cancer: A tertiary academic center experience

ObjectivesCastration-resistant prostate cancer (CRPC) has retained a guarded prognosis, with historical survival estimates of 18 to 24 months. However, the landscape of available therapy has changed, and the emphasis has altered from supportive to active treatment. Few large series from real-world populations exist in the contemporary era with fully mature survival data to confirm the indication based on clinical trials that patients with CRPC are surviving far longer than the historical estimates. We aim to review a large patient cohort with CRPC and provide mature survival data. Methods and materialsUsing the electronic histopathology database at Queen Elizabeth Hospital, Birmingham, UK, all prostate-specific antigentest results between April 2006 and September 2007 were extracted, and patients satisfying the American Society for Radiation Oncology (ASTRO) definition of hormone failure were identified. Electronic records were reviewed and variables were collected, including survival, treatment, biochemistry, histopathology, and demographics. Probability of survival, and of developing metastasis or CRPC, was determined using the Kaplan-Meier method. Patients were stratified into 3 groups, namely, D0—no metastasis at diagnosis but later appearance, D1—no metastasis at diagnosis or at last follow-up, and D2—metastasis at diagnosis. ResultsFrom 8,062 patient–prostate-specific antigen episodes, we identified 447 patients meeting the criteria. A notes review revealed 147 patients with CRPC. Median overall survival (OS) from diagnosis was 84.7 months (95% CI: 73–89), and 129 deaths had occurred (88%). Median OS from diagnosis for D0, D1, and D2 patients was 100.4, 180.1, and 58.9 months, respectively (P< 0.0001), and median OS from CRPC was 40 months (95% CI: 31–58), 82.9 (95% CI: 72–94; P = 0.0125), and 38.7 months (95% CI: 33–46), respectively. One-quarter of patients survived 6 years after development of CRPC. Metastasis is the key prognostic event. ConclusionsSome current international guidelines quote ≤19 months as a survival figure for patients with metastatic CRPC. In our study, median survival is more than double this. We have shown survival more than previously reported figures and believe that these data benefit clinicians and patients in understanding prognosis and treatment choices. Importantly, our patients were diagnosed before the current wave of novel therapeutics for CRPC, so survival for men diagnosed today may be more than our findings.

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.

Optimization of Prostate Biopsy Referral Decisions

Prostate cancer is the most common solid tumor in American men and is screened for using prostate-specific antigen (PSA) tests. We report on a nonstationary partially observable Markov decision process (POMDP) for prostate biopsy referral decisions. The core states are the patients' prostate cancer related health states, and PSA test results are the observations. Transition probabilities and rewards are inferred from the Mayo Clinic Radical Prostatectomy Registry and the medical literature. The objective of our model is to maximize expected quality-adjusted life years. We solve the POMDP model to obtain an age and belief (probability of having prostate cancer) dependent optimal biopsy referral policy. We also prove a number of structural properties including the existence of a control-limit type policy for the biopsy referral decision. Our empirical results demonstrate a nondecreasing belief threshold in age, and we provide sufficient conditions under which PSA screening should be discontinued for older patients. Finally, the benefits of screening under the optimal biopsy referral policy are estimated, and sensitivity analysis is used to prioritize the model parameters that would benefit from additional data collection.

Exploring discordance between biologic and self-reported measures of semen exposure: a qualitative study among female patients attending an STI clinic in Jamaica.

We explored the use of qualitative interviews to discuss discrepancies between two sources of information on unprotected sex: biomarker results and self-reported survey data. The study context was a randomized trial in Kingston, Jamaica examining the effect of STI counseling messages on recent sexual behavior using prostate-specific antigen (PSA) as the primary study outcome. Twenty women were interviewed. Eleven participants were selected because they tested positive for PSA indicating recent semen exposure, yet reported no unprotected sex in a quantitative survey ("discordant"): 5 reported abstinence and 6 reported condom use. Nine participants who also tested positive for PSA but reported unprotected sex in the survey were interviewed for comparison ("concordant"). Qualitative interviews with 6 of the 11 discordant participants provided possible explanations for their PSA test results, and 5 of those were prompted by direct discussion of those results. Rapid PSA testing combined with qualitative interviews provides a novel tool for investigating and complementing self-reported sexual behavior.

Effect of Central Obesity on Prostate Specific Antigen Measured by Computerized Tomography: Related Markers and Prostate Volume

We assessed the effects of central adiposity represented by visceral adipose tissue on prostate volume, prostate specific antigen, and prostate specific antigen mass and mass ratio. This cross-sectional study included 6,389 Asian men 30 to 79 years old. Prostate volume was estimated by transrectal ultrasound. Visceral and subcutaneous adipose tissue was measured by computerized tomography. Multivariate linear regression analysis was done between prostate specific antigen related variables and obesity indexes such as body mass index, waist circumference, and visceral and subcutaneous adipose tissue after adjusting for age. Body mass index, waist circumference and subcutaneous adipose tissue were inversely associated with prostate specific antigen (p for trend <0.001) but visceral adipose tissue showed no associations with prostate specific antigen (p for trend = 0.740). Waist circumference, and visceral and subcutaneous adipose tissue were positively associated with prostate specific antigen mass (p for trend = 0.014, <0.001 and 0.036, respectively). However, body mass index did not show this association (p for trend = 0.372). Body mass index, waist circumference and subcutaneous adipose tissue negatively affected the prostate specific antigen mass ratio (each p for trend <0.05) but there was no such significant correlation for visceral adipose tissue (p for trend = 0.187). When adjusted for visceral adipose tissue body mass index was not associated with prostate volume (p for trend = 0.152) but visceral adipose tissue remained positively associated with prostate volume even after adjusting for body mass index (p for trend = 0.005). Visceral adiposity is the main determining factor of the prostate volume increase and prostate specific antigen production.

Prostate‐specific antigen‐based screening for prostate cancer: Evidence, controversies and future perspectives

The most recent epidemiological survey revealed that the mortality rate for prostate cancer in Japan has increased and has been getting very close to that in the USA, where it has decreased since 1992. The low exposure rate of prostate-specific antigen (PSA) screening in Japan and the high exposure rate of PSA screening in the USA may result in completely deferent trends in the mortality rate of prostate cancer between the two countries. The Japanese Urological Association recommends PSA-based screening for men at risk of prostate cancer at age 50 years or older in general and 45 years or older in men with a family history of prostate cancer within first generation relatives. The fact sheet on screening for prostate cancer should indicate the most recent reliable clinical research on screening for prostate cancer and its demerits including false-negative and false-positive PSA test results and prostate biopsy, overdetection and overtreatment. However, it should be explained to the public that the demerits for PSA screening will be clarified step by step during screening, and in general, men having more information on screening results (PSA level, pathological findings of biopsy specimens, clinical stage, etc.) can understand their current situation better than those having no information on screening results, including PSA levels.

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.

Prostate-Specific Antigen: A Misused and Maligned Prostate Cancer Biomarker

Prostate-Specific Antigen: A Misused and Maligned Prostate Cancer Biomarker

Are Doctors Examining Prostates in University Hospital?

We have observed that serum prostate-specific antigen (PSA) testing is commonly performed for prostate assessment or screening but use of digital rectal examinations (DREs) appears inconsistent. To better define suspected underperformance of DRE, we studied the frequency of combining DRE with PSA testing in prostate assessment. We performed a retrospective study of 197 consecutive patients at a single institution from January 2004 to June 2005 for whom an in-patient urologist consultation was requested. The inclusion criteria were male patients aged 50 years or older with no history of prostate cancer. The mean age of the patients was 62.4 years. Documentation of DREs and PSA testing, reasons for the urologist consultation, and the teams responsible for the patient's hospital care were assessed by a single chart reviewer familiar with the setting and format of the hospital medical records. A total of 89 patients (45.18%) had PSA test results, 50 (25.38%) had DRE findings, and 34 (17.26%) had both DRE findings and PSA test results documented in the hospital medical record during their admission before the urologist consultation. Of 68 surgical patients, 22 (32.35%) had undergone DRE compared with 28 medical patients (21.71%). More medical patients had had PSA testing than had surgical patients (48.06% versus 39.88%). Prostate cancer assessment or screening by combining DRE with PSA testing is often not done by doctors in a teaching university hospital. The underperformance of DRE not only deprives junior doctors of training but also leads to nondetection of some prostate cancer cases.