Interchangeability and diagnostic accuracy of two assays for total and free prostate-specific antigen: two not always related items.

The variation between different PSA assays seems to influence the interpretation of individual PSA values and the clinical decisions about prostate cancer. One reason for this variability could be the different reactivity of antibodies for the various molecular forms of serum PSA; as a result, samples containing the same amount of tPSA but different proportions of fPSA can produce very different values. In this study, serum samples were collected prospectively from 152 consecutive patients referred to 2 institutions (Regional Hospital, Venice, 90 subjects; San Bortolo Hospital, Vicenza, 62 subjects) for PSA elevation and/or symptoms. Serum samples were assessed according to the manufacturers' instructions on the following 2 analyzers: the Immulite 2000 assay (Diagnostic Products Corporation, Los Angeles, USA), which measures tPSA and fPSA, and the ADVIA Centaur (Bayer Diagnostics, Tarrytown, USA), which assays tPSA and cPSA. cPSA values were transformed into fPSA by the equation fPSA=tPSA-cPSA. When taking Immulite tPSA and f/tPSA values as 100%, ADVIA Centaur values were 92.6% and 122%, respectively, which means that 20% of patients would be classified differently according to the traditional biopsy cutoff. In conclusion, there are considerable differences between the 2 methods, which could affect clinical decisions.

Clinical evaluation of percent free prostate-specific antigen using the AxSYM system in the best analytical scenario.

OBJECTIVE: Percent free prostate-specific antigen (PSA) is a promising tool for prostate cancer (CaP) diagnosis. However, its diagnostic performances have not yet been established. The present study was carried out with the aim of evaluating percent free PSA in the most favourable analytical conditions. MATERIALS AND METHODS: Eighty-eight patients affected by newly diagnosed, untreated, primary CaP, and 169 cases with biopsy-confirmed, untreated, benign prostatic hypertrophy (BPH) were prospectively enrolled. Abbott AxSYM total and free PSA were measured by the same technician using the same instrument and the same reagent batch. RESULTS: Percent free PSA was more effective than total PSA in differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. In cases with total PSA >4 microg/l, percent free PSA could have reduced by about 50% the rate of unnecessary biopsies with a probably still acceptable 93% cancer detection rate. The likelihood of CaP after the determination of percent free PSA was in fact higher than 50% using cut-off points which provide low sensitivity values (i.e. 58% in men aged 50-59 years). CONCLUSIONS: Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/l and in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 microg/l. However, percent free PSA should be cautiously interpreted in decision making in individual patients since post-test probability is relatively low in men aged 50-70 years.

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study.

PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

Percent free prostate-specific antigen in assessing the probability of prostate cancer under optimal analytical conditions.

Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA >/=4 microg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50-70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 microg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50-70 years of age.

Prostate cancer probability after total PSA and percent free PSA determination.

UNLABELLED: The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions. MATERIALS AND METHODS: 81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch. RESULTS: The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA > or = 4 ng/mL and > or = 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range. CONCLUSIONS: The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.

Preliminary results of clinical evaluation of the free/total prostate-specific antigen ratio in a multicentric study.

AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Standardization of assay for cytokeratin-related tumor marker CYFRA21.1 in urine samples.

The determination of tumor markers in urine samples has been proposed as an effective diagnostic tool in bladder cancer. The aim of the present investigation was to validate in urine samples the assay of the CYFRA21.1 cytokeratin-related marker, the serum concentrations of which showed promising diagnostic utility in patients with bladder cancer. First-voided urine samples were collected from patients with different malignancies. CYFRA21.1 was assayed with a commercially available enzyme immunoassay (Boehringer Mannheim). Different centrifugation patterns, the use of different buffers and nonionic detergents, and pH variations were evaluated. We demonstrated that: (a) cells and cell debris contain a large amount of CYFRA21.1 and must be eliminated by centrifugation; (b) storage at -20 degrees C causes amorphous precipitate, which may aspecifically bind CYFRA21.1; (c) the latter behavior may be prevented by diluting fresh urine samples with phosphate buffer with nonionic detergent added; (d) pH variations within the range 4.9-8.2 do not significantly affect CYFRA21.1 assay results. Provided that samples are diluted with buffer containing nonionic detergent, the CYFRA21.1 assay showed good precision and accuracy characteristic in urine samples. We therefore propose a standard protocol for the collection of urine samples for CYFRA21.1 assay. In a preliminary clinical evaluation, CYFRA21.1 concentrations in 16 patients with primary bladder cancer were higher than in healthy subjects. In the urine collected in the follow-up of patients treated for bladder cancer, CYFRA21.1 tended to be higher in relapsed patients than in those without evidence of disease. These preliminary data induced us to extend the clinical trial to establish the actual role of this assay in routine use.

Third-generation PSA: ultrasensitive or ultraprecise assay?

The ultrasensitive PSA assay has been recently acknowledged as a useful tool for the monitoring of patients prostatectomized for prostatic cancer. We have evaluated a commercially available ultrasensitive PSA assay (Immulite Third Generation PSA-DPC-Los Angeles CA) in comparison with the routinely used PSA (Immulite PSA-DPC-Los Angeles CA). When evaluated with different approaches, the analytical sensitivity of ultrasensitive PSA ranged between 0.0029 and 0.0038 ng/ml. The biological detection limit was 0.0098 ng/ml. Dilution of samples with low PSA levels showed a good recovery (from 88 to 113%) up to 1:128 dilution factor (final PSA levels ranging from 0.004 to 0.016 ng/ml in different samples). The assay precision was excellent in the low dose range, the highest interassay interadjustment CV among replicates being 5.84% when assaying serum samples with PSA lower than 1.0 ng/ml. Besides its role in the follow-up of prostatectomized patients, the evaluated ultrasensitive PSA could be reliably used for the detection of clinically meaningful PSA variations in the low dose range, and it could therefore be a candidate for the assessment of PSA velocity.

Prostate-specific antigen as a unique routine test in monitoring therapy for inoperable prostate cancer: comparison with radionuclide bone scan and prostatic acid phosphatase.

The aim of the present investigation was the evaluation of cost-effectiveness of variables used in monitoring patients with inoperable prostate cancer. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and radionuclide bone scan were considered. The tumor marker positivity was assessed according to dynamic criteria (> 50% increase between consecutive samples). 108 patients entered the study; 72 patients treated with a luteinizing hormone-releasing hormone analogue were followed up for periods ranging from 12 to 64 months. PSA and PAP levels were measured using immunometric assays. Both cutoff-based and dynamic, serial sample-based decision criteria were employed. With respect to a positive bone scan, PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points. Progression of the disease to the bone occurred in 20 patients: in 17 PSA was the first indicator of progression, in the other 3 PAP anticipated PSA for a very short time (3-4 months), which was not of relevance to clinical decisions. PAP is less specific and sensitive than PSA; PAP may eventually provide information on disease status in a limited percentage of patients with advanced prostate cancer treated with androgen ablation, being differently regulated with respect to PSA. No increasing PSA profile was detected in patients who responded to the therapy. From the results of the present investigation, we draw the following conclusions: (1) PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease, and (2) dynamic criteria of evaluation of serial PSA determinations probably provide more effective and earlier clinical information.

Relationship between prostatic acid phosphatase and prostate-specific antigen serum levels and prostatic volume in benign prostate hyperplasia. Pitfall on tumor markers assessment in primary prostatic cancer?

Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured in 78 patients with benign prostate hyperplasia and compared with both the gland weight and the glandular component of prostatic tissue. Both PAP and PSA were significantly higher where prostate was heavier; however, we could not find a consistent factor which could correlate weight increase to marker levels. PSA tended to be higher when glandular component was more expressed. From the present findings we conclude that in patients with prostate cancer, PAP and PSA serum levels should be investigated considering also the benign components of prostate gland.