Racial and Ethnic Disparities in the Use of Prostate Magnetic Resonance Imaging Following an Elevated Prostate-Specific Antigen Test.

Importance: Prostate cancer screening and diagnosis exhibit known racial and ethnic disparities. Whether these disparities persist in prostate magnetic resonance imaging (MRI) utilization after elevated prostate-specific antigen (PSA) results is poorly understood. Objective: To assess potential racial and ethnic disparities in prostate MRI utilization following elevated PSA results. Design, Setting, and Participants: This cohort study of 794 809 insured US men was drawn from deidentified medical claims between January 2011 and December 2017 obtained from a commercial claims database. Eligible participants were aged 40 years and older and received a single PSA result and no prior PSA screening or prostate MRI claims. Analysis was performed in January 2021. Main Outcomes and Measures: Multivariable logistic regression was used to examine associations between elevated PSA results and follow-up prostate MRI. For patients receiving prostate MRI, multivariable regressions were estimated for the time between PSA and subsequent prostate MRI. PSA thresholds explored included PSA levels above 2.5 ng/mL, 4 ng/mL, and 10 ng/mL. Analyses were stratified by race, ethnicity, and age. Results: Of 794 809 participants, 51 500 (6.5%) had PSA levels above 4 ng/mL; of these, 1524 (3.0%) underwent prostate MRI within 180 days. In this sample, mean (SD) age was 59.8 (11.3) years (range 40-89 years); 31 350 (3.9%) were Asian, 75 935 (9.6%) were Black, 107 956 (13.6%) were Hispanic, and 455 214 (57.3%) were White. Compared with White patients, Black patients with PSA levels above 4 ng/mL and 10 ng/mL were 24.1% (odds ratio [OR], 0.78; 95% CI, 0.65-0.89) and 35.0% (OR, 0.65; 95% CI, 0.50-0.85) less likely to undergo subsequent prostate MRI, respectively. Asian patients with PSA levels higher than 4 ng/mL (OR, 0.76; 95% CI, 0.58-0.99) and Hispanic patients with PSA levels above 10 ng/mL (OR, 0.77; 95% CI, 0.59-0.99) were also less likely to undergo subsequent prostate MRI compared with White patients. Black patients between ages 65 and 74 years with PSA above 4 ng/mL and 10 ng/mL were 23.6% (OR, 0.76; 95% CI, 0.64-0.91) and 43.9% (OR, 0.56; 95% CI, 0.35-0.91) less likely to undergo MRI, respectively. Race and ethnicity were not significantly associated with mean time between PSA and MRI. Conclusions and Relevance: Among men with elevated PSA results, racial and ethnic disparities were evident in subsequent prostate MRI utilization and were more pronounced at higher PSA thresholds. Further research is needed to better understand and mitigate physician decision-making biases and other potential sources of disparities in prostate cancer diagnosis and management.

Low-Value Care at the Actionable Level of Individual Health Systems.

Importance: Low-value health care remains prevalent in the US despite decades of work to measure and reduce such care. Efforts have been only modestly effective in part because the measurement of low-value care has largely been restricted to the national or regional level, limiting actionability. Objectives: To measure and report low-value care use across and within individual health systems and identify system characteristics associated with higher use using Medicare administrative data. Design, Setting, and Participants: This retrospective cohort study of health system-attributed Medicare beneficiaries was conducted among 556 health systems in the Agency for Healthcare Research and Quality Compendium of US Health Systems and included system-attributed beneficiaries who were older than 65 years, continuously enrolled in Medicare Parts A and B for at least 12 months in 2016 or 2017, and eligible for specific low-value services. Statistical analysis was conducted from January 26 to July 15, 2021. Main Outcomes and Measures: Use of 41 individual low-value services and a composite measure of the 28 most common services among system-attributed beneficiaries, standardized to distance from the mean value. Measures were based on the Milliman MedInsight Health Waste Calculator and published claims-based definitions. Results: Across 556 health systems serving a total of 11 637 763 beneficiaries, the mean (SD) use of each of the 41 low-value services ranged from 0% (0.01%) to 28% (4%) of eligible beneficiaries. The most common low-value services were preoperative laboratory testing (mean [SD] rate, 28% [4%] of eligible beneficiaries), prostate-specific antigen testing in men older than 70 years (mean [SD] rate, 27% [8%]), and use of antipsychotic medications in patients with dementia (mean [SD] rate, 24% [8%]). In multivariable analysis, the health system characteristics associated with higher use of low-value care were smaller proportion of primary care physicians (adjusted composite score, 0.15 [95% CI, 0.04-0.26] for systems with less than the median percentage of primary care physicians vs -0.16 [95% CI, -0.27 to -0.05] for those with more than the median percentage of primary care physicians; P < .001), no major teaching hospital (adjusted composite, 0.10 [95% CI, -0.01 to 0.20] without a teaching hospital vs -0.18 [95% CI, -0.34 to -0.02] with a teaching hospital; P = .01), larger proportion of non-White patients (adjusted composite, 0.15 [95% CI, -0.02 to 0.32] for systems with >20% of non-White beneficiaries vs -0.06 [95% CI, -0.16 to 0.03] for systems with ≤20% of non-White beneficiaries; P = .04), headquartered in the South or West (adjusted composite, 0.28 [95% CI, 0.14-0.43] for the South and 0.22 [95% CI, 0.02-0.42] for the West compared with -0.09 [95% CI, -0.26 to 0.08] for the Northeast and -0.44 [95% CI, -0.60 to -0.28] for the Midwest; P < .001), and serving areas with more health care spending (adjusted composite, 0.23 [95% CI, 0.11-0.35] for areas above the median level of spending vs -0.24 [95% CI, -0.36 to -0.12] for areas below the median level of spending; P < .001). Conclusions and Relevance: The findings of this large cohort study suggest that system-level measurement and reporting of specific low-value services is feasible, enables cross-system comparisons, and reveals a broad range of low-value care use.

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States.

OBJECTIVES: For men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States. METHODS: We used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers-PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)-were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies. RESULTS: Biopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively. CONCLUSIONS: Using PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.

Racial Disparities in Prostate Specific Antigen Screening and Referral to Urology in a Large, Integrated Health Care System: A Retrospective Cohort Study.

PURPOSE: Contemporary trends and racial disparities in prostate cancer screening and referral to urology for prostate cancer risk are not well characterized, despite consensus that Black men are at higher risk for poor prostate cancer outcomes. The objective of this study was to characterize current racial disparities in prostate cancer screening and referral from primary care to urology for prostate cancer concern within our large, integrated health care system. MATERIALS AND METHODS: This retrospective cohort study used data from Atrium Health's enterprise data warehouse, which includes patient information from more than 900 care locations across North Carolina, South Carolina and Georgia. We included all men seen in the ambulatory or outpatient setting between 2014 and 2019 who were ≥40 years old. Clinical and demographic data were collected for all men, including age and race. Racial outcomes were reported for all groups with >2% representation in the population. Between-group comparisons were determined using chi-squared analysis, Wilcoxon rank sum testing and multivariable logistic regression, with significance defined as p <0.05. RESULTS: We observed a significant decrease in prostate specific antigen testing across all age and racial groups in a cohort of 606,985 men at Atrium Health, including 87,189 Black men, with an overall relative decline of 56%. As compared to White men, Black men were more likely to undergo prostate specific antigen testing (adjusted OR 1.24, 95% CI 1.22-1.26) and be referred to urology for prostate cancer (adjusted OR 1.94, 95% CI 1.75-2.16). CONCLUSIONS: There was a continued significant decline in prostate cancer screening between 2014 and 2019. Despite having modestly elevated odds of being screened for prostate cancer compared to White men, Black men are relatively underscreened when considering that those who undergo prostate specific antigen screening are more likely to be referred by primary care to urology for additional prostate cancer diagnostic evaluation.

The cost-effectiveness of prostate cancer screening using the Stockholm3 test.

OBJECTIVES: The European Randomized Study of Screening for Prostate Cancer found that prostate-specific antigen (PSA) screening reduced prostate cancer mortality, however the costs and harms from screening may outweigh any mortality reduction. Compared with screening using the PSA test alone, using the Stockholm3 Model (S3M) as a reflex test for PSA ≥ 1 ng/mL has the same sensitivity for Gleason score ≥ 7 cancers while the relative positive fractions for Gleason score 6 cancers and no cancer were 0.83 and 0.56, respectively. The cost-effectiveness of the S3M test has not previously been assessed. METHODS: We undertook a cost-effectiveness analysis from a lifetime societal perspective. Using a microsimulation model, we simulated for: (i) no prostate cancer screening; (ii) screening using the PSA test; and (iii) screening using the S3M test as a reflex test for PSA values ≥ 1, 1.5 and 2 ng/mL. Screening strategies included quadrennial re-testing for ages 55-69 years performed by a general practitioner. Discounted costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Comparing S3M with a reflex threshold of 2 ng/mL with screening using the PSA test, S3M had increased effectiveness, reduced lifetime biopsies by 30%, and increased societal costs by 0.4%. Relative to the PSA test, the S3M reflex thresholds of 1, 1.5 and 2 ng/mL had ICERs of 170,000, 60,000 and 6,000 EUR/QALY, respectively. The S3M test was more cost-effective at higher biopsy costs. CONCLUSIONS: Prostate cancer screening using the S3M test for men with an initial PSA ≥ 2.0 ng/mL was cost-effective compared with screening using the PSA test alone.

Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer.

BACKGROUND: Molecular imaging with novel radiotracers is changing the treatment landscape in prostate cancer (PCa). Currently, standard of care includes either conventional and molecular imaging at time of biochemical recurrence (BCR). This study evaluated the determinants of and cost associated with utilization of molecular imaging for BCR PCa. METHODS: This is a retrospective observational cohort study among men with BCR PCa from June 2018 to May 2019. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET and Prostate Specific Membrane Antigen PET) as part of diagnostic work-up for BCR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost within a 1-year time frame. RESULTS: The study sample included 234 patients; 79.1% White, 2.1% Black, 8.5% Asian/Pacific Islander, and 10.3% Other. The majority were 55 years or older (97.9%) and publicly insured (74.8%). Analysis indicated a one-unit reduction in PSA is associated with 1.3 times higher likelihood of receiving molecular imaging (p < 0.01). Analysis found that privately insured patients were associated with approximately $500,000 more in hospital reimbursement (p < 0.01) as compared to the publicly insured. Additionally, a one-unit increase in PSA is associated with $6254 increase in hospital reimbursement or an increase in total payments by 2.1% (p < 0.05). CONCLUSIONS: Higher PSA was associated with lower likelihood for molecular imaging and higher cost in a one-year time frame. Higher cost was also associated with private insurance, but there was no clear relationship between insurance type and imaging type.

Electrochemically Controlled ATRP for Cleavage-Based Electrochemical Detection of the Prostate-Specific Antigen at Femtomolar Level Concentrations.

As a single-chain glycoprotein with endopeptidase activity, the prostate-specific antigen (PSA) is valuable as an informative serum marker in diagnosing, staging, and prognosis of prostate cancer. In this report, an electrochemical biosensor based on the target-induced cleavage of a specific peptide substrate (PSA peptide) is designed for the highly selective detection of PSA at the femtomolar level, using electrochemically controlled atom transfer radical polymerization (eATRP) as a method for signal amplification. The PSA peptides, without free carboxyl sites, are attached to the gold surface via the N-terminal cysteine residue. The target-induced cleavage of PSA peptides results in the generation of carboxyl sites, to which the alkyl halide initiator α-bromophenylacetic acid (BPAA) is linked via the Zr(IV) linkers. Subsequently, the potentiostatic eATRP of ferrocenylmethyl methacrylate (FcMMA, as the monomer) leads to the surface-initiated grafting of high-density ferrocenyl polymers. As a result, a large amount of Fc redox tags can be recruited for signal amplification, through which the limit of detection (LOD) for PSA can be down to 3.2 fM. As the recognition element, the PSA peptide is easy to synthesize, chemically and thermally stable, and low-cost. Without the necessity of enzyme or nanoparticle labels, the eATRP-based amplification method is easy to operate and low-cost. Results also show that the cleavage-based electrochemical PSA biosensor is highly selective and applicable to PSA detection in complex biological samples. In view of these merits, the integration of the eATRP-based amplification method into cleavage-based recognition is believed to hold great promise for the electrochemical detection of PSA in clinical applications.

Cost-Effectiveness Analysis of Prostate-Specific Antigen Screening Among Chinese Men.

OBJECTIVES: To analyze the cost-effectiveness of prostate cancer screening among Chinese men. METHODS: A cost-effectiveness analysis was performed from a societal perspective using a Markov model to compare 2 strategies: the population-based screening strategy and the current clinical diagnostic strategy. Relevant parameters were retrieved from published literature data and surveys, and univariate sensitivity analysis was used to assess the robustness of the model. We simulated the health outcomes for the next 25 years for 100 000 men and calculated the incremental cost-effectiveness ratio (ICER). RESULTS: This study found that the population-based screening strategy, compared with the clinical diagnostic strategy, could save 756.61 quality-adjusted life-years (QALYs) for the hypothetical population. The ICER for the population-based screening strategy was ¥14 747.11/QALY, and this value was less than the willingness-to-pay threshold of ¥64 520. With life-year gains (LYGs) as the model output, the population-based screening strategy yielded an ICER of ¥16 470.45/LYG. The univariate sensitivity analyses showed that the ICER was sensitive to the prostate-specific antigen (PSA) test fee, the proportion diagnosed with low-grade prostate cancer (PC) in the population-based strategy, and the proportion diagnosed with intermediate-grade PC in the population-based strategy. CONCLUSIONS: Prostate cancer screening based on PSA test results appears to be cost-effective for Chinese men who are in good health and have a life expectancy of more than 10 years. Nevertheless, this finding needs to be further studied with more treatment cost parameters (treatment costs related to impotence and urinary incontinence) and using local utility value information.

Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.

BACKGROUND: The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening. METHODS AND FINDINGS: A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose. CONCLUSIONS: Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness.

Are Men Making Informed Decisions According to the Prostate-Specific Antigen Test Guidelines? Analysis of the 2015 Behavioral Risk Factor Surveillance System.

The prostate-specific antigen (PSA) screening recommendation endorses the opportunity for men to make an informed decision about whether or not to screen. This entails speaking with a provider to discuss the potential advantages, disadvantages, and uncertainties about the PSA screening test. The purpose of this study was to examine (a) the reported level of being informed about the PSA test by race and (b) the association between the receipt of the PSA test and participants reporting that they were informed about the test. U.S. adult males (ages 40-74 years) were identified from the 2015 Behavioral Risk Factors Surveillance System (BRFSS; n = 3,877). Chi-square analysis assessed bivariate differences among men who received different levels of PSA screening information. Binomial logistic regression models assessed the relationship of race/ethnicity and the receipt of the PSA test on being informed about the PSA test. Over half (54.3%) of the sample had a PSA test and most (72.0%) reported that they did not receive information about both the advantages and disadvantages (being informed) of the PSA test. Black men (40.3%) were significantly most likely to report being informed ( p < .001), and 61.3% reported receipt of a recommendation from their provider ( p < .001). White men (63.1%) were significantly more likely to report receiving the PSA test. Findings indicate that more men reported receiving the PSA test than men who reported being informed about it. Future research and interventions should strive for men of all racial and ethnic backgrounds to be informed about the PSA test before making a decision.

Claros System: A Rapid Microfluidics-Based Point-of-Care System for Quantitative Prostate Specific Antigen Analysis from Finger-Stick Blood.

INTRODUCTION: Determination of circulating prostate specific antigen (PSA) is commonly used in the diagnosis and treatment monitoring of prostate cancer [1]. Presently, PSA testing is performed in centralized laboratories, which is associated with prolonged time between venipuncture and the PSA value being available. In this prospective study, we present a new and rapid test system for the quantitative determination of PSA levels from finger-stick blood. METHODS: The Claros1® analyzer is a rapid microfluidics-based point-of-care system for quantitative PSA analysis from 10-µl finger-stick blood that requires only 10 min for testing. Total PSA concentrations by the Claros system in 100 consecutive asymptomatic men (median age 57 years, range 44-81 years) were compared with two commercially available, commonly used PSA assays (Abbott and Elecsys by Roche) performed by a reference laboratory. RESULTS: Eighty-six percent of finger-stick blood-borne probes from 100 men were evaluable for PSA testing by the Claros1® analyzer system. In 13/14 cases the expiry date of the microfluid cassettes of the Claros system was exceeded and one blood puncture was performed inadequately. The correlations between the Claros results and OPKO-Abbott and OPKO-Roche assay results were high, with R2 values of 0.982 and 0.985, respectively. The R2 value for the Roche-Abbott correlation was 0.991 with a slope value of 1.160. Prostate cancer was diagnosed in seven cases, with a median PSA of 1.8 ng/ml in the Claros group compared to 1.75 ng/ml and 2.1 ng/ml in the Abbott and Roche groups, respectively. CONCLUSION: The Claros1® PSA assay combines the advantages of rapid, accurate detection with a low required sample volume, allowing the analysis to be performed using finger-stick blood. Provided that further analysis proves the reproducibility of the test, it may help to reduce the number of office visits, thus decreasing costs to the health care system.

Exnovation of Low Value Care: A Decade of Prostate-Specific Antigen Screening Practices.

OBJECTIVES: To examine prostate-specific antigen (PSA) screening practice change in subgroups of men defined in guidelines and in various regions and to identify factors associated with change in screening practices. DESIGN: Observational study using serial cross-sections, 2003 to 2013. SETTING: National fee-for-service Medicare. PARTICIPANTS: Men aged 68 and older eligible for prostate cancer screening. MEASUREMENTS: National PSA screening practices in men aged 68 and older from 2003 to 2013 and change in regional screening rates in men aged 75 and older. RESULTS: The PSA screening rate in men aged 68 and older was 17.2% in 2003, 22.3% in 2008, and 18.6% in 2013 (p < .001 for all differences); rates ended slightly lower than rates in 2003 only in men 80 and older. Racial disparities in screening became less pronounced over this period. In men aged 75 and older, change in regional screening rates varied widely, with absolute rates growing by 15 per 100 enrollees in some areas and declining by the same amount in others. Areas with high social capital, a measure associated with diffusion of new ideas, were more likely to decline; malpractice intensity and managed care penetration had no effect. CONCLUSION: Studying Medicare enrollees over time, we found little reduction in PSA screening and even increases according to race and in some regions. The heterogeneous changes across regions suggest that consistent reduction in the use of low-value care may require change strategies that go beyond evidence and guidelines to include monitoring and feedback on performance. J Am Geriatr Soc 67:29-36, 2019.

Prostate Cancer Differentiation and Aggressiveness: Assessment With a Radiomic-Based Model vs. PI-RADS v2.

BACKGROUND: Multiparametric MRI (mp-MRI) combined with machine-aided approaches have shown high accuracy and sensitivity in prostate cancer (PCa) diagnosis. However, radiomics-based analysis has not been thoroughly compared with Prostate Imaging and Reporting and Data System version 2 (PI-RADS v2) scores. PURPOSE: To develop and validate a radiomics-based model for differentiating PCa and assessing its aggressiveness compared with PI-RADS v2 scores. STUDY TYPE: Retrospective. POPULATION: In all, 182 patients with biopsy-proven PCa and 199 patients with a biopsy-proven absence of cancer were enrolled in our study. FIELD STRENGTH/SEQUENCE: Conventional and diffusion-weighted MR images (b values = 0, 1000 sec/mm2 ) were acquired on a 3.0T MR scanner. ASSESSMENT: A total of 396 features and 385 features were extracted from apparent diffusion coefficient (ADC) images and T2 WI, respectively. A predictive model was constructed for differentiating PCa from non-PCa and high-grade from low-grade PCa. The diagnostic performance of each radiomics-based model was compared with that of the PI-RADS v2 scores. STATISTICAL TESTS: A radiomics-based predictive model was constructed by logistic regression analysis. 70% of the patients were assigned to the training group, and the remaining were assigned to the validation group. The diagnostic efficacy was analyzed with receiver operating characteristic (ROC) in both the training and validation groups. RESULTS: For PCa versus non-PCa, the validation model had an area under the ROC curve (AUC) of 0.985, 0.982, and 0.999 with T2 WI, ADC, and T2 WI&ADC features, respectively. For low-grade versus high-grade PCa, the validation model had an AUC of 0.865, 0.888, and 0.93 with T2 WI, ADC, and T2 WI&ADC features, respectively. PI-RADS v2 had an AUC of 0.867 in differentiating PCa from non-PCa and an AUC of 0.763 in differentiating high-grade from low-grade PCa. DATA CONCLUSION: Both the T2 WI- and ADC-based radiomics models showed high diagnostic efficacy and outperformed the PI-RADS v2 scores in distinguishing cancerous vs. noncancerous prostate tissue and high-grade vs. low-grade PCa. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:875-884.

Nonlinear joint models for individual dynamic prediction of risk of death using Hamiltonian Monte Carlo: application to metastatic prostate cancer.

BACKGROUND: Joint models of longitudinal and time-to-event data are increasingly used to perform individual dynamic prediction of a risk of event. However the difficulty to perform inference in nonlinear models and to calculate the distribution of individual parameters has long limited this approach to linear mixed-effect models for the longitudinal part. Here we use a Bayesian algorithm and a nonlinear joint model to calculate individual dynamic predictions. We apply this approach to predict the risk of death in metastatic castration-resistant prostate cancer (mCRPC) patients with frequent Prostate-Specific Antigen (PSA) measurements. METHODS: A joint model is built using a large population of 400 mCRPC patients where PSA kinetics is described by a biexponential function and the hazard function is a PSA-dependent function. Using Hamiltonian Monte Carlo algorithm implemented in Stan software and the estimated population parameters in this population as priors, the a posteriori distribution of the hazard function is computed for a new patient knowing his PSA measurements until a given landmark time. Time-dependent area under the ROC curve (AUC) and Brier score are derived to assess discrimination and calibration of the model predictions, first on 200 simulated patients and then on 196 real patients that are not included to build the model. RESULTS: Satisfying coverage probabilities of Monte Carlo prediction intervals are obtained for longitudinal and hazard functions. Individual dynamic predictions provide good predictive performances for landmark times larger than 12 months and horizon time of up to 18 months for both simulated and real data. CONCLUSIONS: As nonlinear joint models can characterize the kinetics of biomarkers and their link with a time-to-event, this approach could be useful to improve patient's follow-up and the early detection of most at risk patients.

Initial Experience with Volumetric 68Ga-PSMA I&T PET/CT for Assessment of Whole-Body Tumor Burden as a Quantitative Imaging Biomarker in Patients with Prostate Cancer.

A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic prostate cancer, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated whether prostate-specific membrane antigen (PSMA) ligand PET/CT may be applied to provide PSMA-derived volumetric parameters for quantification of whole-body tumor burden. Methods: One hundred one patients who underwent 68Ga-PSMA I&T PET/CT because of increasing prostate-specific antigen (PSA) levels after radical prostatectomy were included in this retrospective analysis. Tracer uptake was quantified using SUVs. Volumetric parameters, that is, PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA), were calculated for each patient using a 3-dimensional segmentation and computerized volumetry technique and compared with serum PSA levels. In a group of 10 patients, volumetric parameters were applied for treatment monitoring. Results: Volumetric parameters, that is, whole-body PSMA-TV and whole-body TL-PSMA, demonstrated a statistically significant correlation with PSA levels (P < 0.0001) as a surrogate marker of tumor burden, whereas SUVmax (P = 0.22) or SUVmean (P = 0.45) did not. Treatment response and treatment failure were paralleled by concordant changes in both whole-body PSMA-TV and whole-body TL-PSMA (P = 0.02), whereas neither the change in SUVmax (P = 1.0) nor the change in SUVmean (P = 1.0) concordantly paralleled changes in PSA levels. Conclusion: PSMA-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, capable of standardizing quantitative changes in PET imaging of patients with metastatic prostate cancer and of facilitating therapy monitoring.

Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Assessment of the vaginal residence time of biomarkers of semen exposure.

OBJECTIVE: The primary objective of this pilot study is to determine and compare the residence time in the vagina of biomarkers of semen exposure for up to 15 days post exposure. The biomarkers are prostate-specific antigen (PSA), Y chromosome DNA, the sex determining region of the Y chromosome (SRY) and testis-specific protein Y-encoded 4 (TSPY4). The secondary objectives are to determine if biomarker concentrations differed between intercourse and inoculation groups, to establish whether the sampling frequency post exposure affected biomarker concentrations and decay profile and to determine if biomarker concentrations in vaginal swabs obtained by the participant at home were similar to swabs obtained by the nurse in the clinic. STUDY DESIGN: We randomized healthy women to unprotected intercourse (n=17) versus vaginal inoculation with the male partner's semen in the clinic (n=16). Women were then further randomized to have vaginal swabs obtained at either 7 or 4 time points after semen exposure, up to 15 days post exposure, either obtained at home by the participant or in the clinic by the research nurse. RESULTS: PSA and SRY were markers of recent semen exposure. TSPY4 was detectable in approximately 50% of participants at 15 days post exposure. Unprotected intercourse resulted in significantly higher concentrations of select biomarkers. Sampling frequency and home versus clinic sampling had no significant effect on biomarker concentrations. CONCLUSIONS: Objective biomarkers of recent or distant semen exposure may have great utility for verifying protocol compliance in a variety of clinical trials.

Impact of multiparametric magnetic resonance imaging on risk group assessment of patients with prostate cancer addressed to external beam radiation therapy.

PURPOSE: To investigate the impact of multiparametric magnetic resonance imaging (mpMRI) on risk group assessment of patients with prostate cancer (PCa) initially addressed to external beam radiation therapy (EBRT). MATERIALS AND METHODS: We prospectively performed mpMRI (3.0Tsystem) in 44 patients addressed to EBRT, using a multiparametric protocol (high-resolution multiplanar T2-weighted, diffusion-weighted and dynamic contrast-enhanced imaging). Risk group was assessed in accordance with the National comprehensive cancer network (NCCN) categories, by combining prostate-specific-antigen level, Gleason score and the T-stage as established by digital rectal examination (clinical risk assessment; c-RA) versus mpMRI (mpMRI-risk assessment; mpMRI-RA). The agreement between c-RA and mpMRI-RA was investigated using Cohen's kappa. RESULTS: Patients were included in very low/low risk, intermediate risk, high risk, very high risk and metastatic NCCN categories in 10 (22.7%), 18 (40.9%), 15 (34.1%), 1 (2.3%) and 0 cases using c-RA vs. 8 (18.2%), 14 (31.8%), 14 (31.8%), 4 (9.1%) and 4 (9.1%) cases using mpMRI-RA, respectively, with only moderate agreement (k=0.43). mpMRI-RA determined risk downgrading in 2/44 patients (4.5%), and risk upgrading in 16/44 patients (36.3%). After mpMRI, EBRT remained indicated in all patients. CONCLUSION: mpMRI changed clinical risk stratification in about 41% of patients with PCa, with potential impact on EBRT planning.

Association of GPs' risk attitudes, level of empathy, and burnout status with PSA testing in primary care.

BACKGROUND: Rates of prostate specific antigen (PSA) test ordering vary among GPs. AIM: To examine whether GPs' risk attitude, level of empathy, and burnout status are associated with PSA testing. DESIGN AND SETTING: Register and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis. METHOD: PSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs' risk attitudes, empathy, and burnout status from a 2012 survey. RESULTS: Patients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk-taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test. CONCLUSION: Various aspects of GPs' risk-taking attitudes were associated with patients' probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing.