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.

[Measurements of PSA and of vitamin D: a period of 3-months of use of special forms based on the guidelines of the Haute autorité de santé shows a clear improvement of prescription behaviors]. / Dosages de PSA et de vitamine D : nette amélioration des pratiques professionnelles après 3 mois d'utilisation de formulaires spéciaux fondés sur les recommandations de la HAS.

In France practice guidelines of the Haute Autorité de santé (HAS) are not implemented as often as they should. As a consequence resources are wasted that could be useful elsewhere. In Avril 2014 prescription-forms were introduced in our hospital for PSA and for vitamin-D. If those forms were not filled-in by the physicians, then PSA and vitamin-D were not measured any more by our laboratory. PSA was measured in only two circumstances: therapeutic follow-up of, or screening for, prostate cancer. Patients had to give their formal consent for being screened with PSA. Vitamin-D was measured in the only six circumstances recommended by the HAS. After a few months of use of these two forms we observe a sharp decrease in PSA, and even more so in vitamin D, measurements. Our prescription-forms' legitimacy is high because they are based on governmental guidelines. All the more since the values that are promoted in these guidelines clearly cover the four core principles of bioethics, that is beneficence, non-malevolence, respect for the patient's autonomy (particularly for PSA) and equity. Our results need to be confirmed over a longer period of time, and to be analysed in more detail, particularly regarding the way consent forms are filled-in by the patients.

Population-based assessment of prostate-specific antigen testing for prostate cancer in the elderly.

OBJECTIVES: To perform a population-based analysis to characterize the effect of prostate-specific antigen (PSA) testing on oncologic outcomes in men diagnosed with prostate cancer. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare-linked data to identify 98,883 men diagnosed with prostate cancer from 1996 to 2007. We stratified frequency of PSA testing as none, 1 to 2, 3 to 5, and≥6 tests in the 5 years before prostate cancer diagnosis. We used propensity scoring methods to assess the effect of frequency of PSA testing on likelihood of (1) metastases at diagnosis and (2) overall mortality and prostate cancer-specific mortality. RESULTS: In adjusted analyses, the likelihood of being diagnosed with metastatic prostate cancer decreased with greater frequency of PSA testing (none, 10.6; 1-2, 8.3; 3-5, 3.7; and≥6, 2.5 events per 100 person years, P<0.001). Additionally, greater frequency of PSA testing was associated with improved overall survival and prostate cancer-specific survival (P<0.001 for both). CONCLUSIONS: Greater frequency of PSA testing in men 70 years of age or older in the 5 years before prostate cancer diagnosis is associated with lower likelihood of being diagnosed with metastatic prostate cancer and improved overall and prostate cancer-specific survival.

The cost implications of prostate cancer screening in the Medicare population.

BACKGROUND: Recent debate about prostate-specific antigen (PSA)-based testing for prostate cancer screening among older men has rarely considered the cost of screening. METHODS: A population-based cohort of male Medicare beneficiaries aged 66 to 99 years, who had never been diagnosed with prostate cancer at the end of 2006 (n = 94,652), was assembled, and they were followed for 3 years to assess the cost of PSA screening and downstream procedures (biopsy, pathologic analysis, and hospitalization due to biopsy complications) at both the national and the hospital referral region (HRR) level. RESULTS: Approximately 51.2% of men received PSA screening tests during the 3-year period, with 2.9% undergoing biopsy. The annual expenditures on prostate cancer screening by the national fee-for-service Medicare program were $447 million in 2009 US dollars. The mean annual screening cost at the HRR level ranged from $17 to $62 per beneficiary. Downstream biopsy-related procedures accounted for 72% of the overall screening costs and varied significantly across regions. Compared with men residing in HRRs that were in the lowest quartile for screening expenditures, men living in the highest HRR quartile were significantly more likely to be diagnosed with prostate cancer of any stage (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] = 1.07-1.35) and localized cancer (IRR = 1.30, 95% CI = 1.15-1.47). The IRR for regional/metastasized cancer was also elevated, although not statistically significant (IRR = 1.31, 95% CI = 0.81-2.11). CONCLUSIONS: Medicare prostate cancer screening-related expenditures are substantial, vary considerably across regions, and are positively associated with rates of cancer diagnosis.

Purification of human tissue prokallikrein excreted from insect cells by liquid chromatography.

Tissue kallikrein, generally existing in living bodies as prokallikrein, is a serine proteinase that has proven of great significance to treat hypertension, cardiopathy and nephropathy. Although the extraction of tissue kallikrein from human urine is the most commonly used method to obtain such a protein, not only the yield is very little, but also the procedure is rather complex. Furthermore, the biological safety is uncertain. Therefore, the preparation of such a protein by genetic engineering method, including gene expression, cell culture, separation and purification, is very important. In this paper, a new method to obtain purified tissue prokallikrein excreted from insect cells by liquid chromatography has been proposed. In contrast to the previously published papers, the purification procedure is simplified to only three steps with the final yield of 57% and the purity of 95%, which is not only convenient, but also low-cost and suitable for the large-scale preparation of such a protein. The purified protein is further validated as prokallikrein by high performance liquid chromatography-mass spectrometry and amino acid sequencing.

High-throughput screening of enzyme inhibitors: simultaneous determination of tight-binding inhibition constants and enzyme concentration.

Active site titration by a reversible tight-binding inhibitor normally depends on prior knowledge of the inhibition constant. Conversely, the determination of tight-binding inhibition constants normally requires prior knowledge of the active enzyme concentration. Often, neither of these quantities is known with sufficient accuracy. This paper describes experimental conditions under which both the enzyme active site concentration and the tight-binding inhibition constant can be determined simultaneously from a single dose-response curve. Representative experimental data are shown for the inhibition of human kallikrein.

Issues in the assessment of prostate-specific antigen immunoassays. An update.

Prostate-specific antigen (PSA) immunoassays continue to provide unique and valuable information in the early diagnosis and clinical management of prostate cancer. During the past few years there has been considerable progress in the standardization of routine PSA assays and an emergence of PSA assays with novel applications. The authors discuss these developments and provide some insight when assessing the nuances of assay performance and clinical value.

Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme-linked differential antibody immunosorbent assay.

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF-deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF-deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time-dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.