Total PSA Assay Research Articles

Using Sigma metrics to establish analytical product performance requirements and optimize analytical performance of an in vitro diagnostic assay using a theoretical total PSA assay as an example.

IntroductionEstablishing analytical performance requirements for in vitro diagnostic (IVD) assays is a challenging process. Manufacturers try to optimize analytical performance by choosing amongst many combinations of different product performance characteristics. Sigma metrics and method decision charts can be helpful aids in choosing appropriate analytical performance requirements. The objective of this research was to demonstrate the use of Sigma metrics and method decision charts to help establish analytical performance requirements and to optimize analytical performance at medical decision concentrations for an IVD assay.Materials and methodsA range of possible Sigma metrics were determined using three sources for total allowable error (TEa) and hypothetical total PSA assay results. Method decision charts were created for each TEa source and used to identify the maximum precision and bias that the assay could have to maintain sigma level performance of at least 3.ResultsTo achieve a sigma performance level of at least 3 for a hypothetical total PSA assay, the maximum allowable coefficient of variation ranged from 5.0% to 11.2% depending on the TEa source. To achieve a sigma performance level of at least 6, the maximum allowable coefficient of variation ranged from 2.5% to 5.6% depending on the TEa source.ConclusionsUsing Sigma metrics and method decision charts when establishing analytical performance requirements can help manufacturers choose product requirements that will optimize IVD assay product performance.

Determination of Total PSA Using Magnetic Beads and a Re‐usable Screen Printed Carbon Electrode Array

AbstractA total PSA (tPSA) assay using magnetic beads (1 µm) and a re‐usable 8‐channel screen printed electrochemical array is here reported. The reaction scheme is based on a one step sandwich assay. The linear range obtained is comprised between 5 and 100 ng/mL of tPSA and have a limit of detection of 1.86 ng/mL. This methodology was validated, performing determination of tPSA in serum and the results were compared with a commercial ELISA kit.

The Use of Free-Total Prostate Specific Antigen Ratio in Screening Prostate Cancer in Men with Specific Elevations of Prostate Specific Antigen

Aim: To evaluate the diagnostic performance of free-total PSA ratio using the criteria of total PSA > 4.0 ng/ml as the cut-off for prostate cancer diagnosis in men. Method: A total of sixty patients (mean age 58.03 ± 9.82) were recruited as test subjects from the cancer unit of National Obstetric Fistula Center (NOFIC), Abakaliki, Ebonyi State, Nigeria. All the patients had total PSA value above 4.0ng/ml. Free and total PSA estimations were done using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Result: Free-total PSA ratio indicated high sensitivity (98.2% and 98.2%), specificity (87.9% and 82.9%) and positive predictive values (93.3% and 90%) for detecting undiagnosed prostate cancer at cut-offs of 0.25 and 0.19 respectively. High sensitivity (97.6%) and moderate specificity (61.7%) and positive predictive value (70.0%) were observed at cut off of 0.10. Using the free-total PSA ratio cut-off of ≤ 0.10 for prostate cancer, 70% of the test subjects were diagnosed of prostate cancer, on the other hand when a cutoff of > 0.25 was used, 6.7% of the test subjects were diagnosed of a possible benign prostatic hyperplasia. Conclusion: Free-total PSA ratio is a highly sensitive, specific and useful diagnostic tool alternative to total PSA assay for the screening of undiagnosed prostate cancer. Furthermore, it is highly predictive of the risk for developing prostate cancer at specific cutoff levels.

Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus

We evaluated the analytical performance of a new one-step rapid quantitative sandwich immunoassay for total prostate-specific antigen (tPSA), the FREND™ PSA Plus (FREND PSA) (NanoEnTek Inc., Seoul, Korea). The imprecision, linearity, hook effect, detection limit (LoD), and interference were evaluated and trueness verification and matrix validation were performed. For method comparison, 79 patient specimens were analyzed with FREND PSA and two comparative tPSA assays (Architect® total PSA and cobas® total PSA assay). Total CVs of the imprecision for low (0.208 ng/mL), medium (4.051 ng/mL), and high PSA levels (5.469 ng/mL) were 15.9%, 6.4%, and 9.1%, respectively. Linearity was observed from 1.01 to 19.15 ng/mL and the hook phenomenon was absent up to 171.48 ng/mL. The LoD was 0.094 ng/mL. The regression equations between FREND (y) and Architect or cobas were as follows: y=0.0133+1.054x (r=0.973), y=-0.2144+1.066x (r=0.977), respectively. Differences between FREND PSA and the comparative methods at a medical decision level of 4.0 ng/mL were less than the optimum specification bias (9.3%). The percentage biases from the trueness verification and interference test were less than the desirable specifications for bias (18.7%). The plasma tPSA level measured with lithium heparin or K2EDTA was comparable to that in the serum. The FREND PSA provided reliable analytical performance and test results in comparison to two widely used tPSA assays. It is a simple and rapid test for tPSA and can be applied in point-of-care testing.

CLSI EP17-A protocol: A useful tool for better understanding the low end performance of total prostate-specific antigen assays

BackgroundClinical Laboratory and Standards Institute (CLSI) published EP17-A guideline, recommending new definitions for low end performances: Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ). The aim of this study was to determine LoB, LoD and LoQ by applying EP17-A to Hybritech and World Health Organization (WHO) calibrated Access Total PSA assays, and verify the correlation between results generated by the same reagent with both calibrations, particularly at low end concentrations. MethodsAccording to EP17-A, serum pools of anonymous routine patient samples residuals were analyzed on a UniCelDxI800 with the chemiluminescent Access®Hybritech®TotalPSA assay. ResultsLoB: 0.0046μg/L Hybritech, 0.005μg/L WHO calibration; LoD: 0.014μg/L Hybritech, 0.015μg/L WHO; LoQ at 20% coefficient of variation (CV%) 0.0414μg/L Hybritech, 0.034μg/L WHO. Regression Hybritech y=0.2398×+4.2017 (R2=0.9515); WHO y=0.2248×+3.4335 (R2=0.9596) with no statistical difference. Comparison between Hybritech and WHO at low PSA levels indicated an excellent Pearson's and intraclass correlation (r=0.999, p<0.001; ICC=0.974, p<0.001). ConclusionsOur results show that the Access Total PSA assay is suitable for prostate cancer recurrence and PSA velocity evaluation; Hybritech and WHO calibrated values can both be used for clinical purposes even at low levels.

Prostate Cancer Early Detection

Because guidelines for the early detection of prostate cancer were developed by the ACS in the early 1990s, many variants of the total PSA assay have been introduced in attempts to increase the sensitivity of screening programs (cancer detection) while maintaining their specificity (elimination of unnecessary biopsies). Again, it is important to note that the NCCN guidelines recommend a method by which individuals and their physicians can use these new methods rationally for the early detection of prostate cancer. These guidelines are not designed to provide an argument for the use of early detection programs for prostate cancer. Rather, they are meant to provide a vehicle by which early detection efforts can be practiced in an evidence-based, systematic fashion in patients who choose to participate in such programs. The NCCN guidelines incorporate many new validated findings in addition to the DRE and PSA test. These new factors include percent-free PSA, PSA velocity, PSA testing intervals, biopsy pathology, and TRUS-guided biopsy techniques. The panel will re-examine the clinical utility of these new modalities annually and the guidelines will be modified accordingly. In addition, future iterations of these guidelines may incorporate new serum markers currently undergoing clinical investigation. It is the hope of the NCCN and this guideline panel that these algorithms will achieve the goal of assisting patients and clinicians who are choosing a program of early detection for prostate cancer to make decisions regarding the need for prostate biopsy. Any clinician who uses these guidelines is expected to exercise independent medical judgment in the context of the individual clinical circumstances to determine the patient's need for prostate biopsy. These guidelines will continue to evolve as the field of prostate cancer advances.

Internal validation of an artificial neural network for prostate biopsy outcome

To carry out an internal validation of the retrospectively trained artificial neural network (ANN) 'ProstataClass'. A prospectively collected database of 393 patients undergoing 8-12 core prostate biopsy was analyzed. Data of these patients were applied to the online available ANN 'ProstataClass' using the Elecsys total prostate-specific antigen (tPSA) and free PSA (fPSA) assays. Beside the internal validation of the ANN 'ProstataClass' an additional ANN (named as ANN internal validation: ANNiv) only using the 393 prospective patient data was evaluated. The new ANN model was constructed with the MATLAB Neural Network Toolbox. Diagnostic accuracy was evaluated by receiver operator characteristic (ROC) curves comparing the areas under the ROC curves (AUC) and specificities at 90% and 95% sensitivity. Within a tPSA range of 1.0-22.8 ng/mL, 229 men (58.3%) had prostate cancer (PCa). tPSA, %fPSA and the number of positive digital rectal examinations (DRE) differed significantly from the cohort of patients of the ANN 'ProstataClass', whereas age and prostate volume were comparable. AUCs for tPSA, %fPSA and the ANN 'ProstataClass' were 0.527, 0.726 and 0.747 (P = 0.085 between %fPSA and ANN). The AUC of the ANNiv (0.754) was significantly better compared with %fPSA (P = 0.021), whereas the AUC of two ANN models built on external cohorts (0.726 and 0.729) showed no differences to %fPSA and the other ANN models. Significant differences of DRE status and %fPSA medians decrease the power of the 'ProstataClass' ANN in the internal validation cohort. The effect of retrospective data evaluation the 'ProstataClass' cohort and prospective fPSA measurement may be responsible for %fPSA differences. All ANN models built with different PSA and fPSA assays performed equally if applied to the two cohorts.

Prostate cancer screening: clinical impact of WHO calibration of Beckman Coulter Access® prostate-specific antigen assays

The goal of this study was to evaluate the clinical impact of using the same total prostate-specific antigen (tPSA) and free PSA (fPSA) assays calibrated with World Health Organization (WHO) materials or with Hybritech Tandem-R calibrator. From the initial correlation study that included 150 patients, the clinical impact of the WHO calibration was simulated using a large cohort (n=4548) of referred patients. Interim reports of the European Study of Screening for Prostate Cancer (ERSPC) were used to evaluate the clinical outcomes of patients and the risk of prostate cancer (PCa). WHO calibration of tPSA assays leads to a reduction of about 20% in measured results (tPSA WHO=0.81 tPSA Hybritech+0.04; fPSA WHO=0.78 fPSA Hybritech+0.00; %fPSA WHO=0.92 %fPSA Hybritech+0.00). The simulation showed that the WHO calibration is associated with a risk of missing 15% of PCa. The discrepancies between the two calibrations lead to significant clinical misinterpretation with decreased detection of PCa if tPSA cut-off thresholds are not adjusted.

Benign Prostatic Hyperplasia-associated Free Prostate-specific Antigen Improves Detection of Prostate Cancer in an Artificial Neural Network

To show discriminative power between patients with prostate cancer (PCa) and those with "no evidence of malignancy" using "benign" prostate-specific antigen (bPSA) and the new automated Access benign prostatic hyperplasia-associated (BPHA) research assay within a percent free PSA (%fPSA)-based artificial neural network (ANN) model. The sera from 287 patients with PCa and 254 patients with no evidence of malignancy were measured using the BPHA, total PSA (tPSA), and fPSA assays with Access immunoassay technology, with a 0-10 ng/mL tPSA range. Two ANN models with Bayesian regularization and leave-one-out validation using the 4 input parameters of tPSA, %fPSA, age, and prostate volume and 1 containing BPHA/tPSA were constructed and compared by receiver operating characteristic curve analysis. The BPHA/tPSA-based ANN reached the significant greatest area under the receiver operating characteristic curve (AUC 0.81; P = .0004 and P = .0024) and best specificity (53.9% and 44.5%) compared with the ANN without BPHA/tPSA (AUC 0.77; specificity 50% and 40.6%) and %fPSA (AUC 0.77; specificity 40.9% and 27.2%) at 90% and 95% sensitivity, respectively. The AUCs for tPSA (0.58), BPHA (0.55), BPHA/fPSA (0.51), prostate volume (0.69), and BPHA/tPSA (0.69) were significantly lower. Although BPHA as single marker or ratio to tPSA did not improve the diagnostic performance of %fPSA or tPSA, the incorporation of BPHA/tPSA into an ANN model increased the specificity compared with %fPSA by 13% and 17% at 90% and 95% sensitivity, respectively. Thus, the automated BPHA research assay might improve PCa detection when incorporating this new marker into an ANN.

A [‐2]proPSA‐based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases

The aim of this study was to combine the new automated Access [-2]proPSA (p2PSA) assay with a percent free PSA (%fPSA) based artificial neural network (ANN) or logistic regression (LR) model to enhance discrimination between patients with prostate cancer (PCa) and with no evidence of malignancy (NEM) and to detect aggressive PCa. Sera from 311 PCa patients and 275 NEM patients were measured with the p2PSA, total PSA (tPSA) and free PSA (fPSA) assays on Access immunoassay technology (Beckman Coulter, Fullerton, CA) within the 0-30 ng/ml tPSA range. Four hundred seventy-five patients (264 PCa, 211 NEM) had a tPSA of 2-10 ng/ml. LR models and leave-one-out (LOO) ANN models with Bayesian regularization by using tPSA, %fPSA, p2PSA/fPSA (%p2PSA), age and prostate volume were constructed and compared by receiver-operating characteristic (ROC) curve analysis. The ANN and LR model each utilizing %p2PSA, %fPSA, tPSA and age, but without prostate volume, reached the highest AUCs (0.85 and 0.84) and best specificities (ANN: 62.1% and 45.5%; LR: 53.1% and 41.2%) compared with tPSA (22.7% and 11.4%) and %fPSA (45.5% and 26.1%) at 90% and 95% sensitivity. The %p2PSA furthermore distinguished better than tPSA and %fPSA between pT2 and pT3, and Gleason sum <7 and >or=7 PCa. The automated p2PSA assay offers a new tool to improve PCa detection, and especially aggressive PCa detection. Incorporation of %p2PSA into an ANN and LR model further enhances the diagnostic accuracy to differentiate between malignant and non-malignant prostate diseases.

PSA et suivi après traitement du cancer de la prostate

A first serum total PSA assay is recommended during the first three months after treatment. When PSA is detectable, PSA assay should be repeated three months later to confirm this elevation and to estimate the PSA doubling time (PSADT). In the absence of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 ng/ml (or less than 0.07 ng/ml) for the ultrasensitive assay method and less than 0.2 ng/ml for the other methods. In the presence of residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A consensus has been reached to define recurrence as PSA greater than 0.2 ng/ml confirmed on two successive assays. After external beam radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 ng/ml (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 ng or more above the PSA nadir, whether or not it is associated with endocrine therapy. After endocrine therapy, the PSA nadir is correlated with recurrence-free survival. PSA is decreased for a mean of 18 to 24 months followed by a rise in PSA, corresponding to hormone-independence. The time to recurrence or the time to reach the nadir and the PSA doubling time after local therapy with surgery or radiotherapy have a diagnostic value in terms of the site of recurrence, local or metastatic and a prognostic value for survival and response to complementary radiotherapy or endocrine therapy. A PSADT less than eight to 12 months is correlated with a high risk of metastatic recurrence and 10-year mortality. The histological and biochemical characteristics in favour of local recurrence are Gleason score less or equal to seven (3+4), elevation of PSA after a period greater than 12 months and PSADT greater than 10 months. In other cases, recurrence is predominantly metastatic. The risk of demonstrating metastasis in the case of biochemical recurrence after total prostatectomy and before endocrine therapy depends on the PSA level and the PSADT. No consensus has been reached concerning the indication for complementary investigations by bone scan and abdominopelvic CT in patients with biochemical recurrence after treatment of localized cancer without endocrine therapy. However, when PSADT greater than six months, the risk of metastasis is less than 3% even for PSA greater than 30 ng/ml. When PSADT less than six months and PSA greater than 10 ng/ml, the risk of metastasis is close to 50%.

Étude de pratique des médecins généralistes concernant le dépistage individuel du cancer de la prostate

To assess the practices of general practitioners in the Auvergne region concerning individual prostate cancer screening, to compare these practices with published guidelines and to identify those points that are most difficult to perform.An anonymous postal survey using a predefined questionnaire was conducted among 1339 general practitioners in the Auvergne region identified by the URSSAF file on 1st January 2006. This was a declarative survey with no individual financial reward. The questionnaire comprised three aspects: general practitioner identification criteria, screening practices and the doctors' opinion concerning guidelines.The participation rate was 49.1: 98.3% of general practitioners declared that they proposed screening and 89.5% declared that they proposed screening to all men within certain age limits, from 50 to 75 years in 80.8% of cases. Only 4.6% of doctors provided complete preliminary information to their patients. Among the doctors,75.6% combined digital rectal examination and total PSA assay, but in the presence of an abnormality, only 10.5% referred their patients directly to an urologist without prescribing other complementary investigations (first- or second-line). Finally, 53.5% of doctors considered that published guidelines were adapted to their clinical practice.Individual prostate cancer screening is massively proposed, but differences are observed between the doctors' reported practices and official guidelines. This study emphasizes the need to provide patients with clear and complete information and to improve the general practitioners' knowledge on screening tests and patient referral in the case of positive screening tests.

Elevation of cytokine levels in cachectic patients with prostate carcinoma.

Approximately 60-70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1), IL-6, and IL-8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFalpha, IL-1beta, IL-6, and IL-8. The levels of TNFalpha, IL-1beta, IL-6, IL-8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ-confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total-PSA assays were used to determine cytokine and PSA levels, respectively. Levels of TNFalpha, IL-6, and IL-8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFalpha were correlated positively with IL-8, and there was no correlation between PSA levels and any of the cytokine levels. IL-1beta levels were below the limit of detection in all samples. The current results show that levels of TNFalpha, IL-6, and IL-8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia.

Complexed prostate-specific antigen as a staging tool: results based on a multicenter prospective evaluation of complexed prostate-specific antigen in cancer diagnosis

Within a 7-site prospective evaluation of the Bayer complexed prostate-specific antigen PSA (cPSA) assay, we analyzed the ability of cPSA to predict extracapsular extension (ECE) before radical prostatectomy. Included in this analysis were 152 men diagnosed with cancer, who subsequently underwent radical prostatectomy. Sera were tested with the Bayer total PSA (tPSA) and cPSA assays, and the Beckman free PSA (fPSA) and tPSA assays. Treating surgical pathology result as a binary variable (organ confined vs ECE), mean tPSA, cPSA, fPSA/tPSA (f/tPSA) ratios, tPSA density (tPSAD), and cPSA density (cPSAD) were compared by receiver operating characteristic (ROC) curves and univariate analysis. In all, 28 men (18.4%) had pathologically identified ECE. Between those with and without ECE, significant differences were observed for tPSA ( P = 0.0127), cPSA ( P = 0.0120), tPSAD ( P = 0.0001), and cPSAD ( P = 0.0002), but not f/tPSA ( P = 0.3774) or c/tPSA ( P = 0.2882). All tested parameters except f/tPSA ( P = 0.376) and c/tPSA ( P = 0.288) predicted ECE ( P <0.05) by logistic regression. The ROC area under the curve (AUC) was identical for tPSA and cPSA (0.621) and for tPSAD (0.692) and cPSAD (0.691). Kendall-τ correlation coefficients also demonstrated the strongest correlation with ECE for cPSAD and tPSAD. Either alone or as a tPSAD calculation, cPSA carries equivalent staging ability to tPSA. The use of f/tPSA appears to be less effective in staging than either cPSA or tPSA, whereas the use of either cPSAD or tPSAD provides maximal staging accuracy. Therefore, cPSA could be applied as an accurate predictor of ECE independently or in a nomogram along with other predictive variables.

Miniature Single-Particle Immunoassay for Prostate-specific Antigen in Serum Using Recombinant Fab Fragments

Quantitative, miniaturized nucleic acid assays and immunoassays can be developed with single microparticles, microfluorometric detection, and intrinsically fluorescent lanthanide chelates in a multiple assay format to decrease reagent consumption, cost, and assay time. We used recombinant Fab fragments to capture and detect free and total prostate-specific antigen (PSA) from serum in a submicroliter volume single-particle immunoassay. Genetically engineered thiol-Fab or thiolated monoclonal antibodies (mAbs) were covalently attached onto uniformly sized 60-microm maleimide-activated microparticles. Free and total PSA were detected with europium- or terbium-labeled Fab fragments on a single microparticle using a microfluorometer in a time-resolved mode. The detection limit of the free- and total-PSA assays (mean + 3 SD of zero calibrator) was 0.35 microg/L, with a total volume of 330 nL per particle. An excellent correlation was found in microparticle and microtiter-well assays for 21 serum samples: slopes for free and total PSA were 1.06+/-0.03 and 1.03+/-0.02, respectively (S(y|x) = 0.084 and 0.057 microg/L), with intercepts of 0.013+/-0.018 and 0.013+/-0.017 microg/L (R>0.99). Furthermore, the particle-immobilized Fab fragment had a PSA binding capacity 1.5-fold higher than the intact mAb capacity on a single microparticle. Capacity, kinetics, and sensitivity of the Fab fragment and intact mAb assays in the microparticle and microtiter well formats are discussed. With site-specific (cysteine tail) covalent attachment of Fab fragments on a microparticle, subattomole amounts of PSA can be detected quantitatively.

Probability of prostate cancer detection based on results of a multicenter study using the AxSYM free PSA and total PSA assays

Objectives. The determination of the percentage of free prostate-specific antigen (%fPSA) enhances the specificity of prostate cancer (CaP) detection. This study was undertaken to assess the performance of %fPSA in differentiating benign prostate disease from CaP and to determine the CaP probability estimates using the AxSYM Free PSA and AxSYM Total PSA assays. Methods. In this prospective study, 297 men, 50 years old or older, with a total PSA level between 4 and 10 ng/mL and a nonsuspicious digital rectal examination were enrolled at 10 clinical sites. All subjects underwent at least sextant prostate biopsies to establish the diagnosis. fPSA and total PSA (tPSA) levels were determined using the AxSYM Free PSA and AxSYM Total PSA assays. Percent fPSA values were compared with tPSA values to determine the appropriate cutoffs for prostate biopsy and to calculate the CaP probability estimates. Results. The strongest predictor of CaP in a logistic regression model was %fPSA (odds ratio 2.29), which contributed significantly more than age or tPSA to the predictive model. In this study population, a %fPSA cutoff of 26.4% would have detected 96% of subjects with CaP (sensitivity) and would have eliminated 27.4% of unnecessary biopsies (specificity). CaP probability estimates ranged from 9% to 69% and increased as the %fPSA value decreased. Men with a %fPSA level of 10% or lower had a 69% probability of CaP, and men with a %fPSA level of greater than 26% had a 9% probability of CaP. Conclusions. Percent fPSA values can help differentiate CaP from benign prostate disease and reduce unnecessary biopsies in 27% of men 50 years old or older whose digital rectal examination was normal and whose tPSA level was between 4 and 10 ng/mL. A %fPSA result can assist the physician and patient in determining the probability of CaP and assessing the need for prostate biopsy.

Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial

Objectives. In predominately white populations, measurement of the percentage of free prostate-specific antigen (%fPSA) has been shown to enhance the specificity of total PSA testing for prostate cancer while maintaining high sensitivity and to aid in prostate cancer staging. This study evaluated whether the %fPSA cutoff that maintained a 95% sensitivity in a white population yielded the same sensitivity and specificity in a black population and whether %fPSA was useful in predicting postoperative pathologic features in blacks. Methods. We evaluated 647 white and 79 black men, prospectively enrolled at prostate cancer screening and surgical referral centers. Subjects were 50 to 75 years old with digital rectal examination findings that were not suspicious for prostate cancer and total PSA values between 4.0 and 10.0 ng/mL. All had undergone needle biopsy of the prostate. Hybritech’s Tandem total and free PSA assays were used. Results. Ninety-five percent sensitivity was attained with a %fPSA cutoff of 25% in both races. Use of this cutoff could have avoided unnecessary biopsies in 20% of white and 17% of black subjects ( P = 0.69). In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for %fPSA was significantly higher than for total PSA in both blacks (0.76 versus 0.56, P <0.01) and whites (0.70 versus 0.54, P <0.001). In both races, higher %fPSA values indicated a lower risk of cancer and also predicted favorable pathologic features in radical prostatectomy specimens. Conclusions. A 25% fPSA cutoff detected 95% of cancers and reduced unnecessary biopsies in both races. Higher %fPSA values were associated with favorable postoperative histopathologic findings in both races.

Advantages of replacing the total PSA assay with the assay for PSA-alpha 1-antichymotrypsin complex for the screening and management of prostate cancer.

Several advantages become immediately apparent when the prostate specific antigen (PSA, or tPSA) assay is replaced by the assay specific for the serum PSA-alpha 1-antichymotrypsin (PSA-ACT) complex. For instance, random contributions to the tPSA value by various serum minor PSA isoforms can be avoided, making possible the determination of a more accurate relation of the PSA-ACT concentration to the tumor activity. Discrepancies in percent free PSA (% fPSA) values from the same specimens due to the use of different commercial kits also can be eliminated, mainly because the PSA-ACT assay does not have the problems in antibody selection and calibrator preparation usually associated with the tPSA assay. We found that at the present time different cutoffs of % fPSA for the differentiation of BPH from prostate cancer must be established for each individual tPSA assay. Cutoffs established using values from one tPSA assay should not be used for making clinical decisions when their tPSA values are determined by a different kit. Moreover, when we monitored the patients during treatment with serum tPSA, specific fPSA, and specific PSA-ACT complex assays simultaneously, it was clear that any interpretation of the patient's clinical status based on tPSA values alone could be misleading. Because there is less PSA-ACT complex in BPH specimens relative to that found in cancer serum samples, expressing fPSA as "fPSA/PSA-ACT x 100" and measuring PSA-ACT complex concentrations instead of tPSA during screening improve the measurable contrast between BPH and prostate cancer. Although individually modest, collectively these advantages can add up to considerable improvements.

Free and complexed prostate-specific antigen serum ratios to predict probability of primary prostate cancer and benign prostatic hyperplasia

Objectives Ratios of free to total prostate-specific antigen (f/t PSA ratio) improved differentiation of benign prostatic hyperplasia (BPH) from prostate cancer (CaP). Using sera obtained at least 1 month prior to biopsyconfirmed diagnosis and logistic regression adjusted for disease prevalence, probability curves are constructed to predict the presence of CaP. Methods The patient population included 122 (44%) BPH sera and 155 (56%) prostate carcinoma sera collected prior to any therapy. The total PSA range = 2.0–20.0 ng/mL; median age = 69 years. External reference standards for both free and total PSA assays were used to standardize the assays and correct the ratio. Probability curves and tables for cancer incidence were formulated for a subset of the total test population (total PSA range = 2.0–10.0 ng/mL; 98 BPH, 118 CaP patients) by using logistic regression and prior cancer prevalence statistics derived from a published patient screening study. Results Median f/t PSA ratios were 0.18 and 0.12 in the overall sample and 0.19 and 0.12 in the subset for BPH and CaP, respectively ( P = 0.0001). The median total PSA concentrations for BPH and CaP were 5.8 and 6.7 ng/mL when total PSA range = 2.0–20.0 ng/mL and were 4.9 and 5.9 ng/mL when total PSA range = 2.0–10.0, respectively. Conclusions Cancer probability curves were constructed to help guide decisions concerning biopsy and other aspects of prostate cancer disease management. Further validation of this approach in another series of patients is necessary and is planned.