Proportion Of Prostate-specific Antigen Research Articles

Abstract PO-211: Racial disparities in the quality of surgical care among Medicare beneficiaries with prostate cancer

Abstract Background: Black men in the US demonstrate a two-fold increase in prostate cancer mortality compared to men of other races/ethnicities. The aim of this analysis was to understand how access to high quality care—estimated using surgical volume— impacts disparities in prostate cancer mortality between Black and White men with localized prostate cancer. Methods: This is an analysis of a SEER-Medicare cohort of men diagnosed with localized prostate cancer (cT1-4N0M0) managed primarily by radical prostatectomy from 2005-2015. This analysis was restricted to Black and White men due to low representative numbers of men of other races/ethnicities. Social, demographic, and clinical data were obtained. Both facility and provider data were obtained using administrative data in Medicare. Surgical volume for both providers and facilities were stratified into low, medium, and high. Simple descriptive analyses were performed. Multivariable Cox regression analyses was used to assess the relationship between race, surgical volume, and various clinical and social variables. Results: Black men represented 2,070 (7.1%) of the 29,071 men in this cohort. Black men in the cohort had a higher proportion of prostate specific antigen (PSA) greater than 20 ng/mL (7.0% vs 3.6%) and a higher proportion of men with cT1 disease at diagnosis (64.6% vs 56.1%) when compared to White men. Black men were also less likely to be married/partnered (63.5% vs. 79.9%), more likely to reside in an impoverished zip code (43.9% vs. 11.1%), and more likely to have significant comorbidities (7.2% vs. 2.9%). Black men in this cohort were most likely to be treated in the Southern US (42.8% of cases). Black men were more likely to be treated at a minority serving hospital/facility (24.6% vs. 3.1%, p < 0.001), more likely to be treated at a very large hospital/health system (p < 0.001), and less likely to be treated by a high-volume surgeon or facility (7.7% vs. 19.9%, p < 0.001) compared to White men. On multivariable analysis adjusted for race, hospital type, NCI comorbidity index, clinical stage, and prostatectomy volume; black men demonstrated an increased risk of prostate cancer mortality (hazard ratio 1.27, 95% CI 0.94, 1.72) compared to White men. On stratified analysis, there were no racial disparities in cancer-specific mortality among men treated by a high-volume provider/facility. In contrast, Black men treated by a low/medium volume provider/facility had a higher likelihood of prostate cancer related death following surgery (hazard ratio 1.41, 95% CI 1.02, 1.95, p = 0.04). Conclusions: Black Medicare beneficiaries with prostate cancer demonstrate unique patterns of surgical care utilization, with differences noted in the types and surgical volumes—and likely surgical quality—of their health facilities and providers. Our findings suggest that access to high-quality prostate cancer care is an important mediator of racial disparities in prostate cancer, even among men with access to health insurance. Citation Format: Yaw A. Nyame, Sarah K. Holt, Ruth Etzioni, John L. Gore. Racial disparities in the quality of surgical care among Medicare beneficiaries with prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-211.

Prostate Cancer Screening with PSA: Ten Years' Experience of Population Based Early Prostate Cancer Detection Programme in Lithuania.

The aim of this study is to report key performance estimates from the ten years of a population-based prostate cancer screening programme in Lithuania. Retrospective analysis of screening activities recorded in 2006–2015 among men aged 50–74 years was performed. We estimated screening coverage, cancer detection rate, compliance to biopsy, and positive predictive values in each screening round inside and outside the target population. In the first 10 years of screening, 16,061 prostate cancer cases were registered within the screening programme, 10,202 were observed among screened men but reported outside the screening programme, and 1455 prostate cancers were observed in a screening-naïve population. Screening cover reached up to 45.5% of the target population in the recent rounds. The proportion of prostate specific antigen (PSA) test-positive men decreased from 16.9% in 2006 to 10.7% in 2014–2015. Up to 40.0% of PSA test-positive men received a biopsy, of whom 42.0% were positive for prostate cancer. The cancer detection rate was 10.4−15.0% among PSA test-positives and 1.4–1.9% among screened individuals. Screening participants were more likely to be diagnosed with organ-confined disease as compared to non-participants. Despite the unorganized screening practices being employed and low coverage per screening round, 70% of the target population were screened at least once in the first 10 years of screening.

Are the Results of the Prostate Testing for Cancer and Treatment Trial Applicable to Contemporary Prostate Cancer Patients Treated with Radical Prostatectomy? Results from Two High-volume European Institutions

The Prostate Testing for Cancer and Treatment (ProtecT) trial reported excellent outcomes for patients with localized prostate cancer (PCa) managed with radical prostatectomy (RP), radiotherapy, or active monitoring. We aimed at assessing the generalizability of the ProtecT trial to contemporary patients undergoing RP at two high-volume institutions. Overall, 29147 PCa patients treated with RP between 1999 and 2016 were included. We evaluated changes in disease characteristics over time. Competing-risk analyses estimated the 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. Overall, 20598 (71%) patients were eligible for the ProtecT trial, ranging from 76% in 1999–2005 to 67% in 2014–2016. The proportion of prostate-specific antigen (PSA) ≥20ng/ml, biopsy grade group 4–5, and high-risk disease increased over time (all p<0.001). Among men potentially eligible for the ProtecT trial included in our study, median PSA and grade group 4–5 were higher as compared with the ProtecT trial (6.5 vs 4.7ng/ml and 9% vs 2%), especially in individuals treated in more recent years (7.1ng/ml and 16% for 2014–2016). Median follow-up was 50 mo. When considering patients eligible for the ProtecT trial, the 10-yr OCM rate exceeded the CSM rate (7% vs 2%). Conversely, when focusing on patients not eligible due to disease aggressiveness, the risk of CSM exceeded that of OCM (10% vs 7%). Clinicians should carefully consider the inverse stage migration toward more aggressive disease among surgical candidates in more recent years. Individuals not eligible for the ProtecT trial are more likely to die from PCa than from OCM, thus being the optimal candidates for testing the role of primary treatments. Patient summaryContemporary prostate cancer surgery candidates harbor more aggressive disease features at presentation as compared with men included in the Prostate Testing for Cancer and Treatment (ProtecT) trial and are, in turn, at an increased risk of progression and mortality. Clinicians should take this into consideration when generalizing the results of the ProtecT trial with a particular emphasis on the oncologic safety of active monitoring in contemporary patients not included in structured prostate-specific antigen-based screening programs.

Detection of Free Prostate-Specific Antigen Using a Novel Single-Chain Antibody (scAb)-Based Magneto-Immunosensor

The proportion of prostate-specific antigen (PSA) circulating in the free form can help to differentiate prostate cancer from benign prostate disease. In this paper, novel highly specific single-chain antibody (scAb) fragments were conjugated to magnetic particles (MPs) for the recognition and magnetic separation of free PSA (fPSA). A sandwich-type immunoassay method was developed, in which fPSA was captured by the scAb-conjugated MPs and labelled by a secondary antibody, conjugated to horseradish peroxidase (HRP) enzyme. The biosensor was constructed on carbon screen-printed electrodes (SPEs) modified with magnetic particles for increased surface area and fast reaction kinetics, thus enhancing binding capacity. The amperometric response was measured at −0.15 V, using hydrogen peroxide as the HRP substrate and hydroquinone (HQ) as the electrochemical mediator. The magneto-immunosensor demonstrated a sensitivity of 0.5 ng mL−1, with a linear detection range up to 10 ng mL−1 of fPSA.

The Proportion of Prostate-specific Antigen (PSA) Complexed to α1-Antichymotrypsin Improves the Discrimination between Prostate Cancer and Benign Prostatic Hyperplasia in Men with a Total PSA of 10 to 30 μg/L

The aim of this study was to assess the diagnostic accuracy of the proportion of prostate-specific antigen (PSA) complexed to alpha(1)-antichymotrypsin (PSA-alpha(1)ACT:PSA ratio) in the differential diagnosis of prostate cancer (CaP) and benign prostatic hyperplasia (BPH) in men with total PSA of 10-30 microg/L. We used our immunoassays (ELISAs) for total PSA and PSA-alpha(1)ACT complex to study 146 men. In 123, total PSA was between 10 and 20 microg/L; 66 of these had CaP and 57 BPH. In 23 men, total PSA was between 20 and 30 microg/L; 14 of these had CaP and 9 BPH. We calculated the area under the ROC curves (AUC) for total PSA, PSA-alpha(1)ACT complex, and PSA-alpha(1)ACT:PSA ratio, and determined the cutoff points that gave sensitivities approaching 100%. In the total PSA range between 10 and 20 microg/L, the AUC was significantly higher for the PSA-alpha(1)ACT:PSA ratio (0.850) than for total PSA (0.507) and PSA-alpha(1)ACT complex (0.710; P <0.0001). A cutoff ratio of 0.62 would have permitted diagnosis of all 66 patients with CaP (100% sensitivity) and avoided 19% of unnecessary biopsies (11 of 57 patients). In the total PSA range between 20 and 30 microg/L, the AUC for the PSA-alpha(1)ACT:PSA ratio (0.980; 95% confidence interval, 0.82-0.99) was greater than the AUC for total PSA (0.750; 95% confidence interval, 0.51-0.89; P = 0.042). In this range, a cutoff point of 0.64 would have permitted the correct diagnosis of all 14 patients with CaP and 6 of the 9 with BPH. The diagnostic accuracy of the PSA-alpha(1)ACT:PSA ratio persists at high total PSA concentrations, increasing the specificity of total PSA. Prospective studies with large numbers of patients are needed to assess whether the ratio of PSA-alpha(1)ACT to total PSA is a useful tool to avoid unnecessary prostatic biopsy in patients with a total PSA >10 microg/L.

Palladium-103 brachytherapy for prostate carcinoma

Purpose: A report of biochemical outcomes for patients treated with palladium-103 (Pd-103) brachytherapy over a fixed time interval. Methods and Materials: Two hundred thirty patients with clinical stage T1–T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. Kaplan-Meier estimates of biochemical failure on the basis of two consecutive elevations of PSA were utilized. Multivariate risk groups were constructed. Aggregate PSA response by time interval was assessed. Results: The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%. When all 1354 PSA determinations obtained for this cohort were considered, the patients with a proportion of PSAs ≤ 0.5 ng/ml continued to increase until at least 48 months post-therapy. These data conformed to a median PSA half-life of 96.2 days. Conclusions: Prostate brachytherapy with Pd-103 achieves a high rate of biochemical and clinical control in patients with clinically organ-confined disease. PSA response following brachytherapy with low-dose-rate isotopes is protracted.

Characterization and determination of the complex between prostate-specific antigen and α1-protease inhibitor in benign and malignant prostatic diseases

Prostate-specific antigen (PSA) is a tissue-specific serine protease which forms complexes with protease inhibitors such as f 1 -antichymotrypsin and f 2 - macroglobulin. We have studied the interaction between PSA and f 1 -protease inhibitor (API) in vitro and found that 15% of the added PSA binds to API while the majority of API is cleaved between Met358 and Ser359 when PSA is incubated with a 5-fold excess of API at 37 C for 7 days. The complex between PSA and API (PSA- API) formed in vitro displays the same chromatographic behavior, molecular size and immunoreactivity as endogenous PSA- API occurring in serum, indicating that they are identical. PSA- API can be detected in serum by a time-resolved immunofluorometric assay (IFMA), in which a monoclonal antibody to PSA is used as a catcher and a polyclonal antibody to API labeled with a Eu-chelate is used as a tracer. Purified PSA- API formed in vitro is used as a calibrator. PSA- API in serum represents 1.0- 7.9% (median 2.4%) of total PSA (tPSA) in prostate cancer (PCa, n= 82) and 1.3- 12.2% (median 3.6%, p<0.01) in patients with benign prostatic hyperplasia (BPH, n= 66). The IFMA for PSA- API in serum is hampered by a variable background, which is caused by non-specific adsorption of the huge excess of API in serum to the solid phase. The background can be determined by an assay using the same tracer as in the IFMA for PSA- API but PSA-unrelated antibody on the solid phase. The background signal is subtracted from the PSA- API signal. The clinical utility of PSA- API in serum has been evaluated in PSA-positive subjects from the Finnish PCa screening trial. After subtraction of the background, the proportion of PSA- API in relation to tPSA is lower in PCa than in controls, 0.9% vs. 1.6%, respectively (p<0.001). Logistic regression analysis showed that the concentration of PSA- API was independent of the proportion of free PSA as a diagnostic variable among subjects with a tPSA of 4- 10 w g/l (p= 0.009). The probability of PCa calculated by logistic regression using the concentration of PSA- API and the proportion of free PSA in serum significantly improved cancer specificity at high sensitivity levels (85 - 95%) as compared to the proportion of free PSA alone.

Variation in the Quantitation of Prostate-specific Antigen in Reference Material: Differences in Commercial Immunoassays,

Prostate-specific antigen (PSA) is a widely used biochemical marker for prostate cancer (1). PSA, a serine protease, forms complexes with serine protease inhibitors such as α2-macroglobulin and α1-antichymotrypsin (ACT) (2). The major immunoreactive forms of serum PSA are PSA-ACT complex and free PSA. PSA complexed to α2-macroglobulin is not measured by current immunoassays (3). Because the proportion of PSA complexed to ACT is higher in men with prostate cancer than in men with benign prostatic hyperplasia (BPH) (3)(4), the use of a ratio of free-to-total PSA may improve discrimination between men with BPH and prostate cancer (5)(6). Results obtained with different PSA immunoassays are not interchangeable (7)(8)(9)(10). The variation among immunoassays reflects, in large part, the specificity of different PSA antibodies (7). To a lesser extent, the composition of the calibrator, the PSA values assigned to the calibrator, the test diluent, and the physical design of the immunoassays contribute to intermethod differences (6)(7). Assays using a monoclonal-monoclonal sandwich format yield, in general, an equimolar response to free and ACT-complexed PSA, whereas monoclonal-polyclonal formats tend to yield higher values for samples containing greater proportions of free PSA (8). We have recently described the Bayer Immuno 1TM PSA Assay (Bayer Corporation), which uses a monoclonal-polyclonal antibody format that yields an equimolar response to varying proportions of free and complexed PSA (11). This has now been found to be a result of the unique binding properties of the monoclonal antibody used for the capture of PSA (manuscript in submission). Proficiency testing among clinical laboratories has indicated large intermethod variability in the quantitation of total PSA (12). The aim of this study was to determine the magnitude and cause of this intermethod variation. Here we report our multi-site analysis of …

Analytical Performance of Free PSA Immunoassays: Results from an Interlaboratory Survey,

Prostate-specific antigen (PSA) is a glycoprotein that is secreted by the prostate into the seminal fluid. Low concentrations of the protein are normally released into blood, but in prostate cancer (CAP) as well as in a high proportion of subjects with benign prostatic hyperplasia (BPH), serum PSA concentrations frequently increase above normal values (4 μg/L). Therefore, immunoassays measuring serum PSA concentration are routinely carried out to diagnose prostate diseases and to monitor progress of the disease and relapse of CAP after removal of the prostate (1)(2)(3). A few years ago, PSA was reported to be present in serum in three different forms. The predominant molecular form is complexed to α1-antichymotrypsin, whereas a minor fraction circulates in a free noncomplexed form. These two forms are both measured by PSA assay. Only a very small proportion of PSA circulates bound to α2-macroglobulin; this third form, however, is a nonimmunoreactive complex. The free, noncomplexed form of PSA is reported to constitute a minute proportion of the serum PSA in patients with CAP, but to be significantly greater in subjects affected by BPH. On the basis of this observation the simultaneous measurement of total PSA (tPSA) and free PSA (fPSA) has been suggested. The computed ratio fPSA/tPSA is considered a useful tool to better discriminate between BPH subjects and CAP patients and therefore to improve the early diagnosis of CAP (4). …