Systematic Differences Between Total and Free Prostate-Specific Antigen Immunoassays: Comparison Using Passing and Bablok Regression.

Recent studies have shown that there are systematic differences among total and free prostate-specificantigen (PSA) immunoassays. In this study we analyzedintermethod differences in total PSA (tPSA) and free PSA(fPSA) measurement using ARCHITECT i2000SR (Abbott Diagnostics) and COBAS E601 (Roche Diagnostics). A number of 160 blood samples were tested for tPSA and 50 samples for fPSA (selecting only sampleswith tPSA: 4.1-10.0 µg/L). Passing-Bablok regression analysis was used to compare the two analytical methods fortPSA, fPSA and percentage of fPSA (%fPSA). A strong correlation was noticed between ARCHITECT i2000SR and COBAS E601 for tPSA, fPSA and %fPSA (r between 0.94 and 0.99). Concentrations of tPSA and fPSA measured by COBAS E601 were higher thanthose measured by ARCHITECT i2000SR with a bias of 0.8 µg/L for tPSA and 0.14 µg/L for fPSA. Analyzing therelative difference between methods for fPSA and %fPSA, COBAS E601 exceed a 10% relative difference limit. Our study confirms that there are differences in measured concentrations of tPSA and fPSA byvarious commercial methods. Because clinical judgment on subsequent diagnostic procedures, such as prostatebiopsy, is based on tPSA and fPSA results, tests harmonization should be a priority.

Actual Contribution of Free to Total PSA Ratio in Prostate Diseases Differentiation.

OBJECTIVES: To determine significance and sensitivity of the Free to Total prostate specific antigen (PSA) ratio (%fPSA) in diagnosis of prostate cancer and to correlate its sensitivity and specificity with diagnosis. METHODS: Research included 220 patients, who had indication for biopsy (Clinic for Urology, University Clinical Center Sarajevo). RESULTS: Average age of patients was 64.6 ± 8.1 years. Kruskal Wallis test indicates that there is a significant difference in age in relation to the diagnosis (KW χ2=12.508; p=0.006). The correlation between the %fPSA level and diagnosis is positive and statistically significant (r=0.211; p=0.002) in the sense that cancer patients have the lowest %fPSA. Analysis of the sensitivity at 95% specificity of %fPSA compared to particular diagnosis shows the highest sensitivity for prostate cancer - 20.61% (8.35-31.02) with statistically significant AUC p<0.05. Analysis of %fPSA test in detecting prostate cancer, at cut-off values ≤ 0.16, shows a sensitivity of 72.3% and specificity of 50.4 (at cut-off values <0.07, sensitivity is 8.4%, and specificity is 97.8%). CONCLUSION: PSA is organ specific but not cancer specific marker, whose total value, as well as the %fPSA serve as a basis, with a digitorectal exam, in the detection of prostate cancer. By increasing the cut-off values sensitivity of %fPSA increases and specificity decreases. %fPSA has a relative importance in the detection of prostate cancer, and should not be used as a guideline, without prior clinical examination.

Double trouble: Unmasking two hook effects on Siemens Atellica® - Total PSA and total hCG assays.

The "hook effect" or "prozone phenomenon" occurs when the concentration of a particular analyte saturates the antibodies used in the test, resulting in falsely low or negative results despite the presence of high analyte concentrations. We report two recent cases of hook effect encountered with a widely used immunoassay analyzer, the Siemens Atellica® IM1600. The first case involves a patient with advanced metastatic prostate cancer whose total PSA (tPSA) concentration dropped dramatically from his last biological control. The second case concerns a pregnant woman whose total HCG (ThCG) levels were also subject to the hook effect and who was found to have a molar pregnancy. In both cases, a dilution step enabled to overcome this analytical concern and to obtain a correct result. In addition, a comparison of the sensitivity of different immunoassay analyzers to this phenomenon was carried out. To avoid this analytical error, an additional dilution step should automatically be performed when there is a clinical suspicion of elevated levels of tumor or hormone markers. Finally, the most affected manufacturers should adapt their assays, accordingly.

Usefulness of pre-biopsy multiparametric magnetic resonance imaging and clinical variables to reduce initial prostate biopsy in men with suspected clinically localized prostate cancer.

PURPOSE: We evaluated the usefulness of pre-biopsy multiparametric magnetic resonance imaging and clinical variables to decrease initial prostate biopsies. MATERIALS AND METHODS: We prospectively evaluated 351 consecutive men with prostate specific antigen between 2.5 and 20 ng/ml, and/or digital rectal examination suspicious for clinically localized disease. All men underwent pre-biopsy multiparametric magnetic resonance imaging and initial 14 to 29-core biopsy, including anterior sampling. Three definitions of significant cancer were defined based on Gleason score and cancer volume (percent positive core and/or maximum cancer length). The overall cohort was divided into men at low risk-prostate specific antigen less than 10 ng/ml and normal digital rectal examination, and high risk-prostate specific antigen 10 ng/ml or greater and/or abnormal digital rectal examination. We evaluated the frequency of significant cancer according to magnetic resonance imaging and risk categories. Clinical variables as significant cancer predictors were analyzed using logistic regression. The sensitivity, specificity, and positive and negative predictive values of magnetic resonance imaging were calculated with or without clinical variables for significant cancer. RESULTS: The frequency of significant cancer in men with negative vs positive magnetic resonance imaging was 9% to 13% vs 43% to 50% in the low risk group and 47% to 51% vs 68% to 71% in the high risk group. In men at low risk with negative magnetic resonance imaging prostate volume was the only significant predictor of significant cancer. In the low risk group the negative predictive value for significant cancer of a combination of positive magnetic resonance imaging and lower prostate volume (less than 33 ml) was 93.7% to 97.5%. CONCLUSIONS: Pre-biopsy multiparametric magnetic resonance imaging along with prostate volume decreases the number of initial prostate biopsies by discriminating between significant cancer and other cancer in men with prostate specific antigen less than 10 ng/ml and normal digital rectal examination.

Spondin-2, a secreted extracellular matrix protein, is a novel diagnostic biomarker for prostate cancer.

PURPOSE: SPON2 belongs to the F-spondin family of secreted extracellular matrix proteins. It is deregulated in some tumors, including prostate cancer. In this prospective study we assessed the role of serum SPON2 as a biomarker for prostate cancer diagnosis as well as any association between SPON2 levels and clinicopathological features. We also compared the diagnostic performance of this biomarker to that of serum sarcosine, and percent free-to-total and total prostate specific antigen. MATERIALS AND METHODS: SPON2 was measured using a sandwich enzyme linked immunosorbent assay in serum samples from 286 patients with prostate cancer and 68 with no evidence of malignancy, as confirmed by 10 to 12-core ultrasound guided prostate biopsy. Nonparametric statistical tests and ROC analysis were done to assess the diagnostic performance of SPON2 vs the other biomarkers. RESULTS: Median serum SPON2 was significantly higher in patients with prostate cancer than in those with no evidence of malignancy (77.5 vs 23.6 ng/ml, p<0.0001). ROC analysis showed a higher predictive value of SPON2 (AUC 0.952) than of serum sarcosine (AUC 0.674), percent free-to-total prostate specific antigen (AUC 0.806) and total prostate specific antigen (AUC 0.561). Moreover, patients with low grade prostate cancer had higher median SPON2 levels (p=0.001). Spearman rank correlation confirmed a negative association with Gleason score (rs=-0.29, p=0.0005). CONCLUSIONS: We found evidence that SPON2 levels were significantly higher in patients with prostate cancer than in healthy individuals. Moreover, this biomarker had better diagnostic performance than serum sarcosine, and percent free-to-total and total prostate specific antigen. This greater accuracy was also present in a subset of patients with normal prostate specific antigen.

Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy.

PURPOSE: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PURPOSE: Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. MATERIALS AND METHODS: We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). CONCLUSIONS: SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

[Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)]. / Caractéristiques immuno-analytiques du PSA et des biomarqueurs dérivés (PSA total, PSA libre et P2ProPSA).

Prostate-specific antigen (PSA) is the recommended tumor marker for individual screening and follow-up of prostate cancer. This paper reviews main structural and physiological data about prostate specific antigen isoforms: total PSA, free PSA, [-2]proPSA (also named p2PSA). It describes the pre-, per- and post-analytical conditions for these different parameters. It presents the interpretation of results and derived calculated indices (free/total PSA ratio, Prostate Health Index or PHI) for the management of prostate cancer (initial diagnosis and follow-up).

Technical Note: Newly Reformulated Total and Free PSA Immunoassay on Cobas e411 Analyzer Is Virtually Free from Biotin Interference.

OBJECTIVE: Total and free prostate specific antigens (PSA) have been used as diagnostic markers for monitoring progress of therapy in patients with prostate cancer as well as for screening purpose. Roche total and free PSA immunoassay utilizes biotinylated antibody in assay design. As a result, both assays are affected by elevated serum biotin levels. Recently, Roche reformulated these assays to reduce biotin interference. We evaluated biotin interference in these products. MATERIALS AND METHODS: We prepared three serum pools with one pool containing high amount of total PSA. Then aliquots of each serum pool were further supplemented with various concentrations of biotin (100-1500 ng/mL) followed by measuring both total and free PSA using Roche total and free PSA immunoassay and Cobas e411 analyzer. RESULTS: We observed no significant interference of biotin in both total and free PSA assays up to biotin concentration of 1200 ng/mL. CONCLUSION: We concluded that newly reformulated total and free PSA immunoassays are virtually free from biotin interference.

Measurement of total and free prostate specific antigen (PSA) in human serum samples using an ultra-microanalytical system.

Prostate specific antigen (PSA) is a serine protease used for the screening of prostate cancer. The total portion of PSA (tPSA) can be found in its free form (fPSA), or bound to other proteins forming a stable complex. A heterogeneous sandwich-type UltraMicro Enzyme-Linked ImmunoSorbent Assay (UMELISA) has been developed for the measurement of tPSA and fPSA in human serum samples. Strips coated with a high affinity monoclonal antibody (MAb) directed against PSA are used as solid phase, to ensure the specificity of the assay. Biotinylated MAbs specific for tPSA and fPSA ensured sensitivity, given the high affinity binding to streptavidin. The assay was completed in 1.5 h, with a measuring range 0.019-20 µg/L (tPSA), and 0.009-20 µg/L (fPSA). The intra- and inter-assay CV were lower than 9%. Recovery percentages were 96-105%. High correlations were found between the values of the UMELISA PSA standards and the International Reference Standards 96/670 (R2 = 0.9996) and 96/688 (R2 = 0.9989). The assay did not recognize any of the interfering molecules tested. Regression analysis of serum samples showed a good correlation with Roche Elecsys total PSA (n = 631, R2 = 0.986, ρc = 0.992), BioMérieux VIDAS TPSA (n = 631, R2 = 0.989, ρc = 0.993) and Roche Elecsys free PSA (n = 164, R2 = 0.973, ρc = 0.979), all with a relative difference below 15%, and a p < 0.001. A retrospective study of the use of UMELISA PSA in Cuba was carried out. The analytical performance characteristics of UMELISA PSA support its use for the quantification of tPSA and fPSA in human serum samples in a single kit, making it an affordable diagnostic assay available to Cuban Public Health System and developing countries. Between the years 2014-2020, more than 3 million Cuban patients have benefited from the test for free.

The Impact of Cell-free Plasma DNA on Metastatic and Nonmetastatic Prostate Cancer.

Intorductuion: Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. AIMS: Our study aims at assessing the use of cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. METHODS: The study included 180 subjects who were classified into four groups: Group I (GI) included 50 perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were carried out for all groups. RESULTS: Our study revealed that the level of tPSA was significantly higher in prostate cancer patients, while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. CONCLUSION: There was a statistically significant difference in yields of cfDNA between metastatic and non-metastatic groups (P=0.03) with a higher level in the metastatic group.

Screening for prostate cancer: a study on the free and total prostate specific antigen.

BACKGROUND: A variety of biomarkers have been developed to monitor growth of cancerous diseases and to detect them at an early stage. Prostate-specific antigen (PSA) is a valuable prostate cancer biomarker that is now widely used for population screening, diagnosis, and monitoring of patients with prostate cancer. Other factors than prostate cancer can cause elevation of PSA levels therefore, free prostate specific antigen measurements in serum have been proposed in order to improve the specificity of laboratory identification of prostate cancer. AIM: The aim of our study was to evaluate the diagnostic significance of both total PSA and Free PSA in discriminating prostate cancer from other prostate diseases. MATERIALS AND METHODS: Our study group consisted of 1201 males admitted at outpatient clinic aged between 35 and 84 years old (mean age 63 years). All laboratory measurements were performed on serum samples. The data were statistically analyzed by using descriptive statistics for Windows. RESULTS: The mean total PSA concentration evaluated among 1038 patients was 16.17 ng/mL whereas only Free PSA concentration was evaluated in 163 serum samples and resulted in a mean value of 2.67 ng/ml. In order to calculate the correlation between total and free PSA, data among 69 /1038 patients were further analyzed through statistical program software package for data analysis. CONCLUSIONS: Measuring serum free PSA concentrations along with PSA concentrations may provide higher accuracy for detecting prostate cancer and might eliminate unnecessary biopsies in the men with PSA of more than 4.0 ng/mL.

Is serum PSA a predictor of male hypogonadism? Testing the hypothesis.

OBJECTIVE: Male hypogonadism (MH) is common among infertile men. Besides testosterone, limited MH biomarkers are available, while researchers have suggested the use of prostate-specific antigen (PSA) to help diagnose MH. Hence, we sought to evaluate the potential use of PSA to predict MH among relatively young men with infertility in Nigeria. METHODS: The study included 707 male partners (35-44 years) in infertile couples seeking infertility evaluation at a third-level care center in Nigeria. MH was diagnosed using standard guidelines. Receiver operating characteristic (ROC) and regression analyses explored the potential of serum free PSA (fPSA) and total PSA (tPSA) in predicting MH and MH-related clinical features. RESULTS: In all, 29.7% of the patients had MH (MH+ve). The MH+ve group had lower mean values of fPSA and tPSA than the group without MH (MH-ve). The best fPSA threshold of < 0.25 µg/L compared with the best tPSA threshold of < 0.74 µg/L had higher accuracy (area under the curve [AUC] 0.908 versus 0.866, respectively), sensitivity (87% versus 83%, respectively), and specificity (42% versus 37%, respectively) for MH diagnosis. After adjustment for confounders, fPSA level ≤ 0.25 µg/L was more likely to predict MH-related decreased libido (odds ratio [OR] 2.728, p<0.001) and erectile dysfunction (OR 3.925, p<0.001) compared with tPSA ≤ 0.74 µg/L in the MH+ve group. CONCLUSION: For MH diagnosis, fPSA and tPSA had good sensitivity but very poor specificity, although fPSA had better potential for MH diagnosis and association with MH-related clinical features than tPSA. Hence, fPSA could complement other biomarkers for MH diagnosis in men 35-44 years, although we recommend further studies to confirm these findings.

Clinical factors affecting prostate-specific antigen levels in prostate cancer patients undergoing radical prostatectomy: a retrospective study.

BACKGROUND: Since prostate-specific antigen (PSA) levels can be influenced by some routinely available clinical factors, a retrospective study was conducted to explore the influence of obesity, smoking habit, heavy drinking and chronic obstructive pulmonary disease on PSA levels in men with histologically confirmed prostate cancer. PATIENTS & METHODS: We reviewed the medical records of 833 prostate cancer patients undergoing radical prostatectomy. RESULTS: Serum PSA levels at the time of surgery were not associated with either BMI or history of chronic obstructive pulmonary disease or heavy drinking. Conversely, PSA levels were associated with smoking status. CONCLUSION: Among the clinical factors explored in this homogeneous population, only tobacco use was associated with PSA levels, which should be considered when using PSA-based screening in male smokers.

Comparison of Three Assays for Total and Free PSA Using Hybritech and WHO Calibrations.

BACKGROUND/AIM: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. PATIENTS AND METHODS: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods. RESULTS: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). CONCLUSION: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.

The Association between Prostate-Specific Antigen Velocity (PSAV), Value and Acceleration, and of the Free PSA/Total PSA Index or Ratio, with Prostate Conditions.

INTRODUCTION: Prostate-specific antigen velocity (PSAV) is used to monitor men with clinical suspicion of prostate cancer (PCa), with a normal cut-off point of 0.3-0.5 ng/mL/year. The aim of the study is to establish the predictive capacity of PSAV (value and acceleration) and of the free PSA/total PSA index or ratio. METHOD: Prospective multicentre observational study in 2035 men of over 47 years of age. INCLUSION CRITERIA: men who wished to be informed on the health of their prostate. EXCLUSION CRITERIA: men with a previously diagnosed prostate condition. Groups: GA: (n = 518): men with serum PSA equal to or greater than 2.01 ng/mL. GB: (n = 775): men with serum PSA greater than or equal to 0.78 ng/mL and less than 2.01 ng/mL. GC: (n = 742): men with serum PSA less than 0.78 ng/mL. VARIABLES: prostate-specific antigen (PSA); age; body mass index (BMI); PSA velocity (PSAV) (ng/mL per year); free PSA/total PSA index (iPSA); PSAV acceleration (increasing: positive, or decreasing: negative); prostate diagnosis (benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), or infectious and non-infectious prostatitis and prostatic adenocarcinoma (PCa)); de novo diagnoses of urinary tract diseases or conditions; concomitant treatments, diseases and conditions; final diagnosis of prostate health. RESULTS: Mean age 62.35 years (SD 8.12), median 61 (47-94); age was lowest in GC. Mean BMI was 27.89 kg/m2 (SD 3.96), median 27.58 (18.56-57.13); no differences between groups. Mean PSAV was 0.69, SD 2.16, median 0.13 (0.001-34.46); PSAV was lowest in GC. Mean iPSA was 27.39 u/L (SD 14.25), median 24.29 (3.7-115); iPSA was lowest in GA. PSAV had more positive acceleration in GA and more negative acceleration in GC. There were 1600 (78.62%) cases of normal prostate or BPH, 322 (15.82%) cases of PIN or non-infectious prostatitis, and 113 (5.55%) cases of PCa. There were more cases of BPH in GC and more cases of PIN or prostatitis and cancer in GA (p = 0.00001). De novo diagnoses: 15 cases of urinary incontinence (UI), 16 discomfort/pain in LUT, 112 cases of voiding disorders, 12 urethral strictures, 19 hematuria, 51 cystitis, 3 pyelonephritis, 4 pelvic inflammatory disease; no differences were found between groups. In the multivariate analysis, PSAV and the direction of PSAV acceleration (positive or negative) were the variables which were correlated most strongly with prostate health. iPSA was associated with the presence of prostatitis, PCa, and BPH. Men in GA had more prostatitis, PCa, treatment with alpha blockers, and history of previous smoking. GB had more cases of BPH and more positive acceleration of PSAV. GC had more normal prostates, more BPH, more use of ranitidine, and more PSAV with negative acceleration. CONCLUSIONS: PSAV, direction of PSAV acceleration, and iPSA in PSA cut-off points of 0.78 ng/mL and 2.01 ng/mL in a priori healthy men over 47 predict the probability of benign or malignant pathology of the prostate.

[Use of « Reference change value ¼ in medical biology: about two examples: total PSA and hemoglobin]. / Utilisation de la « Reference change value ¼ en biologie médicale : à propos de deux exemples : PSA total et hémoglobine.

The interpretation of the variation between the results of two dosages performed on the same patient is generally quite empirical. It is usually based on the experience of the biologist or physician. Through two examples, total PSA and hemoglobin, we hoped to set up an indicator of the significance variation between results: The Reference change value or RCV to provide assistance to the validator biologist and prescriber based on measured statistical arguments. This article describes the methodology used for the RCV calculation, the formatting on analysis reports and the limitations of the system.

Development and validation of a novel multivariate risk score to guide biopsy decision for the diagnosis of clinically significant prostate cancer.

Objectives: Selecting patients suspected of having prostate cancer (PCa) for a prostate biopsy remains a challenge. Prostate-specific antigen (PSA)-based testing is hampered by its low specificity that often leads to negative biopsy results or detection of clinically insignificant cancers, especially in the 2-10 ng/mL range. The objective was to evaluate a novel diagnostic test called Proclarix incorporating thrombospondin-1 and cathepsin D alongside total and free PSA as well as age for predicting clinically significant PCa. Patients and methods: The test was developed following a retrospective study design using biobanked samples of 955 men from two reference centres. A multivariate approach was used for model development followed by validation to discriminate significant (grade group ≥2) from insignificant or no cancer at biopsy. The test specificity, positive predictive value (PPV) and negative predictive value (NPV) at a fixed sensitivity of 90% were compared to percent free PSA (%fPSA) alone. The number of avoidable prostate biopsies deemed to be representative of clinical utility was also assessed. Results: In the targeted patient population, the test displayed increased diagnostic accuracy compared to %fPSA alone. Application of the established model on 955 patients at a fixed sensitivity of 90% for significant disease resulted in a specificity of 43%, NPV of 95% and a PPV of 25%. This is in comparison to a specificity of 17%, NPV of 89% and PPV of 19% for %fPSA alone and had the potential to reduce the total number of biopsies needed to identify clinically significant cancer. Further, the test score correlated with significance of cancer assessed on prostate biopsy. Conclusions: The Proclarix test can be used as an aid in the decision-making process if to biopsy men in this challenging patient population. The use of the test could reduce the number of biopsies performed avoiding invasive procedures, anxiety, discomfort, pain and complications.

Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL: results from the Göteborg randomized population-based prostate cancer screening trial.

OBJECTIVE: To evaluate the long-term outcome of men with an initial prostate-specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T PSA) ratio is a useful prognostic marker in this range. MATERIALS AND METHODS: This study is based on 5,174 men aged 50-66 years, who in 1995-1996 participated in the first round of the Göteborg randomized screening trial (initial T-PSA level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T PSA screening until they reached the upper age limit (on average 69 years). Biopsy was recommended if PSA ≥ 3 ng/mL. RESULTS: After a median follow-up of 18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of ≤0.99 ng/mL to 26.0% in men with T-PSA levels of 1-1.99 ng/mL and 40.3% in men between 2-2.99 ng/mL (p < 0.001). The initial PSA was also related to the incidence of Gleason ≥7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs 1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of the model (p = 0.371). CONCLUSIONS: Some men with initial PSA < 3 ng/mL will be diagnosed too late, despite participating in an organized screening program, indicating that prompt diagnosis is justified in these men. PC incidence and risk of PC death was associated with PSA., but F/T PSA had no predictive value.

Stability of total prostate-specific antigen and free prostate-specific antigen after 10 years' storage.

INTRODUCTION: PSA is a serine protease composed of 240 amino acids in a single polypeptide chain and is a routine parameter in prostate cancer diagnostics. The aim of our study was to test the long-term stability of tPSA and fPSA after 10 years' storage at -80°C. MATERIALS AND METHODS: We analyzed two aliquots from 55 serum samples. The first was assayed in routine testing at the time of establishing the diagnosis. The second was thawed for further testing after approximately 10 years' storage at -80°C. The mean of storage time was 10.41 years (min-max: 9.35-11.40 years). We compared the results of tPSA and fPSA. We calculated the fPSA/tPSA ratio and compared the results of clinical evaluation. Serum tPSA and fPSA levels were assayed using chemiluminescent kits Access Hybritech PSA and free PSA. All measurements were performed using the instrument UniCel® DxI 800. RESULTS: tPSA decreased 3.59% on average with a correlation r=0.9213, and fPSA increased at an average of 2.41% with a correlation r=0.9338. The fPSA/tPSA ratio increased 0.80% on average with a correlation r=0.9174. On clinical evaluation, five samples had fallen to a less malignant category and three samples had risen to a higher malignant category compared with the original results. CONCLUSION: The stability of tPSA and fPSA levels in serum is sufficient after 10 years' storage at -80°C. Calculation of the fPSA/tPSA ratio is not recommended due to the change in the category of malignancy of 15% of the samples.