Complexed Prostate Specific Antigen Research Articles

Correlation Analysis between Apparent Diffusion Coefficient of Prostate Cancer and other Prostate Cancer Indicators

Background: There are very few reports on the correlation between the apparent diffusion coefficient (ADC) of magnetic resonance parameters and other laboratory indicators of prostate cancer in China, and there is no unified clinical conclusion at present from the other parts of the world. Therefore, this study analyzed the correlation between ADC and laboratory indicators, such as serum total prostate specific antigen (TPSA), complex prostate specific antigen (CPSA), free prostate specific antigen (FPSA), Gleason score, and left and right diameters of the prostate so as to provide a basis for the diagnosis and treatment of prostate cancer. Methods: A total of 104 patients of all age groups with prostate cancer diagnosed in the General Hospital of Wanbei Coal and Electricity Group, Wanbei, China, from January 2017 to December 2022 were retrospectively analyzed as the experimental group. At the same time, 63 patients with benign prostatic hyperplasia who received health examinations were selected as the control group. TPSA, CPSA, FPSA, CPSA/TPSA, FPSA/TPSA, Gleason score, left and right diameters of the prostate, and magnetic resonance parameter ADC were detected in all patients. At the same time, we analyzed the correlation between ADC and other parameters in prostate cancer patients. Results: The serum levels of TPSA, CPSA, and FPSA in prostate cancer patients were significantly higher (P<0.001) than in those in the control group. The differences between CPSA/TPSA and FPSA/TPSA in the two groups were not statistically significant. Meanwhile, ADC and left and right diameters of the prostate were significantly lower in prostate cancer patients than in subjects in the control group, and the differences were statistically significant (P<0.001). In addition, serum TPSA, CPSA, and FPSA in high-risk prostate cancer patients were found to be significantly higher than in cases in the medium-risk and low-risk groups. The results of our study also revealed that ADC was moderately negatively correlated with FPSA (r=-0.415, P<0.001) and weakly negatively correlated with TPSA (r=-0.222, P=0.024). Conclusion: There is a correlation between ADC, TPSA, and FPSA in patients with prostate cancer, and there were significant differences in TPSA, CPSA, and FPSA between patients with prostate cancer and patients with benign prostatic hyperplasia. The three parameters can be combined for the diagnosis of prostate cancer.

Increases in tumor markers are associated with primary Sjögren's syndrome-associated interstitial lung disease.

Aims:Interstitial lung disease (ILD) is the most common type of pulmonary involvement of extraglandular complication in patients with primary Sjögren’s syndrome (pSS), but the diagnosis of pSS-associated ILD (pSS-ILD) is still challenging. This study aimed to investigate the levels of serum tumor markers in pSS patients with or without ILD (pSS-non-ILD) and explore its diagnostic value for pSS-ILD.Methods:A total of 168 pSS-ILD patients and age- and sex-matched 538 pSS-non-ILD were recruited. The levels of peripheral tumor markers, including carbohydrate antigen (CA)153, CA125, CA19-9, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), β-human chorionic gonadotropin, alpha fetoprotein, CA724, and complexed prostate specific antigen, the clinical manifestations, and general laboratory indicators were measured and collected.Results:Compared with pSS-non-ILD, pSS-ILD patients had higher levels of disease activity indicators, such as EULAR Sjögren’s syndrome disease activity index, ESR, and CRP, and elevated serum levels of tumor markers: NSE, CEA, CA125, and CA153. The serum levels of CA153 [odds ratio (OR) = 4.521, 95% confidence interval (CI) = [1.871, 10.928)] and CEA [OR = 2.879, 95% CI = (1.305, 6.353)] were significantly correlated with the onset of SS-ILD. CA153 was the only tumor marker with area under receiver operating characteristic curve (AUC) over 0.7 [AUC = 0.743, 95% CI = (0.70, 0.79)].Conclusion:Tumor markers increased in serum of pSS-ILD patients. Higher CA153 levels are significantly correlated to the increased risk of ILD in patients with pSS and may be directly involved in the pathogenesis of pSS-ILD. Serum CA153 had the best diagnostic value in those tumor markers for pSS-ILD without malignancy.

Serum complexed and free prostate specific antigen levels are lower in female elite athletes in comparison to control women

Background: We hypothesize that prostate specific antigen (PSA), a protein that it is under regulation by androgens, may be differentially expressed in female elite athletes in comparison to control women. Methods: We conducted a cross-sectional study of 106 female athletes and 114 sedentary age-matched controls. Serum from these women was analyzed for complexed prostate specific antigen (cPSA) and free prostate specific antigen (fPSA), by fifth generation assays with limits of detection of around 6 and 140 fg/mL, respectively. A panel of estrogens, androgens and progesterone in the same serum was also quantified by tandem mass spectrometry. Results: Both components of serum PSA (cPSA and fPSA) were lower in the elite athletes vs the control group (P=0.033 and 0.013, respectively). Furthermore, estrone (p=0.003) and estradiol (p=0.004) were significantly lower, and dehydroepiandrosterone (p=0.095) and 5-androstene-3β, 17β-diol (p=0.084) tended to be higher in the athletes vs controls. Oral contraceptive use was similar between groups and significantly associated with increased cPSA and fPSA in athletes (p= 0.046 and 0.009, respectively). PSA fractions were not significantly associated with progesterone changes. The Spearman correlation between cPSA and fPSA in both athletes and controls was 0.75 (P < 0.0001) and 0.64 (P < 0.0001), respectively. Conclusions: Elite athletes have lower complexed and free PSA, higher levels of androgen precursors and lower levels of estrogen in their serum than sedentary control women. Abbreviations: cPSA, complexed PSA; fPSA, free PSA; PCOS, polycystic ovarian syndrome; E1, estrone; E2, estradiol; DHEA, dehydroepiandrosterone, Testo, testosterone; DHT, dihydrotestosterone; PROG, progesterone; Delta 4, androstenedione; Delta 5, androst-5-ene-3β, 17β-diol; BMD, body mineral density; LLOQ, lower limit of quantification; ULOQ, upper limit of quantification; LOD, limit of detection; ACT, α 1-antichymotrypsin

Serum complexed and free prostate specific antigen levels are lower in female elite athletes in comparison to control women.

We hypothesize that prostate specific antigen (PSA), a protein that it is under regulation by androgens, may be differentially expressed in female elite athletes in comparison to control women. We conducted a cross-sectional study of 106 female athletes and 114 sedentary age-matched controls. Serum from these women was analyzed for complexed prostate specific antigen (cPSA) and free prostate specific antigen (fPSA), by fifth generation assays with limits of detection of around 6 and 140 fg/mL, respectively. A panel of estrogens, androgens and progesterone in the same serum was also quantified by tandem mass spectrometry. Results: Both components of serum PSA (cPSA and fPSA) were lower in the elite athletes vs the control group (P=0.033 and 0.013, respectively). Furthermore, estrone (p=0.003) and estradiol (p=0.004) were significantly lower, and dehydroepiandrosterone (p=0.095) and 5-androstene-3β, 17β-diol (p=0.084) tended to be higher in the athletes vs controls. Oral contraceptive use was similar between groups and significantly associated with increased cPSA and fPSA in athletes (p= 0.046 and 0.009, respectively). PSA fractions were not significantly associated with progesterone changes. The Spearman correlation between cPSA and fPSA in both athletes and controls was 0.75 (P < 0.0001) and 0.64 (P < 0.0001), respectively. Conclusions: Elite athletes have lower complexed and free PSA, higher levels of androgen precursors and lower levels of estrogen in their serum than sedentary control women. cPSA, complexed PSA; fPSA, free PSA; PCOS, polycystic ovarian syndrome; E1, estrone; E2, estradiol; DHEA, dehydroepiandrosterone, Testo, testosterone; DHT, dihydrotestosterone; PROG, progesterone; Delta 4, androstenedione; Delta 5, androst-5-ene-3β, 17β-diol; BMD, body mineral density; LLOQ, lower limit of quantification; ULOQ, upper limit of quantification; LOD, limit of detection; ACT, α 1-antichymotrypsin.

Assessment of Serum Prostate Specific Antigen, Some Renal Indices and Uric Acid Levels in Subjects with Benign Prostatic Hyperplasia at Lokoja, Nigeria

Background: Prostate disorders (prostatitis, BPH and Pca) can contribute to renal impairment. Benign prostatic hyperplasia (BPH) and renal impairment (RI) such as chronic kidney disease are important public health problems in older men. The present study aimed to assess serum levels of prostate specific antigen, urea, creatinine, protein and uric acids in subjects with BPH at Federal Medical Center, Lokoja, Kogi State, Nigeria. A population-based sample of one hundred and ten (110) men aged (51-70) years were conveniently recruited and divided into three groups designation A= BPH with RI, (n=35) B=BPH without RI, (n=35) and C=Control, (n=40). Methods: Blood samples were collected from all the participants and serum separated and stored at -20˚C until analyzed for prostate specific antigen using Enzyme Linked Immunosorbent Assay (ELISA) and colorimetric assay method for creatinine, urea, protein and uric acid. Data were analyzed using SPSS software application (version 17.0). Pearson correlation and Receiving Operating Characteristics of the groups were done. Results: The result showed that urea and creatinine levels were significantly higher in BPH subjects with or without renal impairment when compared with controls (p<0.05 respectively). Similarly, total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), complex prostate specific antigen (cPSA) and percent free prostate specific antigen (%fPSA) were significantly higher in BPH subjects with or without RI when compared with controls (p<0.05 respectively). Urea, creatinine and uric acid were significantly higher while total protein was significantly lower in BPH with RI when compared with BPH without RI (p<0.05 respectively). Conclusion: The significantly higher urea, creatinine and uric acid levels in BPH subjects showed that BPH subjects with RI may have decrease excretion and accumulation of uric acid by the kidney suggesting possible risk of progression to CKD while BPH subjects without RI tends to be more prone to developing renal dysfunction. The significant correlation between %fPSA, creatinine and urea shows an association between BPH and renal diseases. Using receiving operating characteristic (ROC) curves to assess diagnostic performance of various parameters in various groups for the prediction of BPH with or without renal disease, there was evidence that fPSA and %fPSA have higher predictive value in the diagnosis of BPH while uric acid, urea, creatinine and protein have higher predictive value in the diagnosis of renal disease. It is therefore, recommended that people with prostate disorders should be screened for renal diseases and vice versa.

The usefulness of complexed prostate–specific antigen in predicting metastasis in patients with prostate cancer

Objective To determine the value of complexed prostate–specific antigen (cPSA) in predicting metastasis in patients with prostate cancer. Methods From January 2012 to April 2014, the clinical data of 74 patients with newly diagnosed prostate cancer in our hospital was retrospective reviewed. The prostate cancer was diagnosed by transrectal ultrasound guided biopsy and postoperative pathologic diagnosis. The patients were divided to 2 groups according to metastases status. There were 38 patients in the group of metastasis and 36 patients in the group of without metastasis. In metastasis group, the bone metastasis was found in 36 cases. There is only one case with lung metastasis and one case with lymph node metastasis. In the group without metastasis, the T stages classification were T1–T2 in 17 cases and T3–T4 in 19 cases. While, 10 cases with T1–T2 stage and 28 cases with T3–T4 stage were confirmed in the group with metastasis. There was no statistical significance of T stages and mean age in two groups (P>0.05). The level of cPSA in the serum was detected by chemiluminescent immunoassay, the level of tPSA, fPSA were detected by electro–chemiluminescent immunoassay. fPSA/tPSA, cPSA/tPSA were evaluated and the corresponding specificity were calculated. The correlation of age with tPSA, cPSA were analysed. The differences in PSA, fPSA/tPSA, cPSA/tPSA were compared between metastasis and non–metastasis group. ROC curve analysis was used to determine the diagnostic value of cPSA and tPSA, In the meantime, area of ROC curves were compared by Z test. Results The age was not related to the value of tPSA (r=–0.09, P=0.12) and cPSA (r=–0.38, P=0.14). The median levels of tPSA, fPSA, and cPSA are 29.88μg/L, 2.18 μg/L and 18.86 μg/L in the group without metastasis, respectively. The median levels of tPSA, fPSA, and cPSA were 410.05 μg/L, 51.50 μg/L and 290.40 μg/L in the group with metastasis, respectively. Significant differences of those results could be found in two groups (P 0.05). The area under the curve of tPSA and cPSA were 0.83 (95%CI 0.73–0.93) and 0.82 (95%CI 0.73–0.92) respectively. Analysis of ROC curves showed that the AUC for cPSA is not significant different from tPSA (Z=1.64, P=0.10). The specificity of cPSA was 22.2% which is higher than that of tPSA (19.4%) at a sensitivity of 92.1% in predicting metastasis comparing with the patients without metastasis. The sensitivity could reach to 90.0% when the cut off value of tPSA was 9μg/L or the cut off value of cPSA was 7 μg/L. Conclusions In our study, a preliminary validation that cPSA is useful for predicting the metastasis in patients with prostate cancer was made. Key words: Prostate cancer; Metastases; Complex prostate–specific antigen

Effects of ejaculation on serum prostate-specific antigen levels

The aim of this study is to evaluate the effect of ejaculation on serum total, free and complex prostate-specific antigen (PSA) levels and their effect on biopsy decisions. Our study includes 47 men older than 45 years with symptomatic benign prostatic hyperplasia (BPH). Patients' PSA levels were under 2.5 ng/mL, and there were no known conditions to preclude ejaculation. Eight patients with similar demographic, and clinical characteristics were chosen as a control group. With three days of sexual abstinence, blood samples were drawn for the measurement of baseline PSA levels, and then the patients were told to ejaculate. One, 5, 24 and 72 hours after ejaculation, serum total, free and complexed PSA levels were measured. Serum PSA sampling was performed at the same intervals in the control group without ejaculation. The mean age of the patients was 59.13±1.38 years in the study group, and 63.75±3.13 years in the control group. The mean international prostate symptom scores (IPSS) were 11.78±1.12 and 11.63±3.32 in the study, and the control groups, respectively. The mean baseline total, free, and complexed PSA values were 1.07±0.09, 0.31±0.03, and 0.71±0.08 ng/mL, respectively. In the study group, total PSA value was found to be 1.29±0.12 ng/mL (p=0.008) at first hour after ejaculation, and this change was statistically significant when compared with baseline values. Mean total PSA level rose up to 1.28±0.13 ng/mL (p=0.05) by the 5(th) hour after ejaculation, but this change was not statistically significant relative to the baseline values. Mean free PSA level rose after the first hour postejaculation to 0.37±0.04 ng/mL (p=0.01) and after the fifth hour postejaculation to 0.37±0.04 ng/mL (p=0.002), and these changes were statistically significant relative to the baseline values. There were no statistically significant changes at the other sampled times as for the total, free or complexed PSA serum levels. When all three values were considered individually, in only 2.12% of the patients, biopsy decisions could be affected by the elevation in PSA levels. When the PSA value is borderline with respect to biopsy decisions, the effect of ejaculation on serum PSA levels may be clinically important. In these patients, ejaculation must be questioned, and repeated. PSA levels should be evaluated 24 hours after ejaculation. There were no statistically significant changes in the levels of complex PSA values. Further studies are needed to clarify the relationship between complexed PSA and ejaculation.

Can Mean Platelet Volume Serve as a Marker for Prostatitis?

Aim: The aim of the study was to compare the yield of mean platelet volume (MPV), total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), f/t PSA ratio and complex prostate specific antigen (cPSA) in patients with prostatitis.Material and method: The study was designed in the Kayseri Education and Research Hospital. Ninety-six patients with prostatitis were enrolled retrospectively into the study. Laboratory data were obtained from the computerized patient database. We evaluated the correlation between tPSA, fPSa, f/t PSA ratio, cPSA, MPV and extent and aggressiveness of inflammation in the surgical specimens of patients who underwent surgery for benign prostatic hyperplasia (BPH). Inflammation in the prostatic tissues was scored for extent and aggressivity of inflammation using the grading system designed by Irani et al.Results: The total PSA, fPSa, f/t PSA ratio, cPSA and pre- and post-treatment MPV values of each group did not differ (p>0.05) (Table 1). Also there was no correlation between the histopathological grades and the MPV, tPSA, fPSA, f/t PSA ratio and cPSA of patients. However, MPV values significantly decreased after treatment in all grades of prostatitis (p<0.001).Conclusion: MPV values may be used as an inflammation marker in patients with prostatitis.

Use of Prostate-Specific Antigen (PSA) Isoforms For The Detection of Prostate Cancer in Men With a Psa Level Of 3-10 Ng/Ml: A Zimbabwean Perspective

Total PSA (tPSA) has been used to diagnose prostate cancer although its performance as a screening test has several limitations including limited specificity. The main objective of the study was to determine the use of the PSA isoforms (free PSA, complex PSA and ratio of free/total PSA) in diagnosing prostate cancer among Zimbabwea men with tPSA levels between 3 and 10 ng/ml. A cross sectional study was done on 44 men attending a Urology Clinic at Harare Hospital (mean age = 70yrs). If tPSA was between 3 and 10ng/ml and the attending urologist requested a prostate biopsy a written consent was sought and the sample was analyzed for free and complexed PSA (cPSA). A follow up was made on the biopsy results. Statistical methods were then used to determine the use of the PSA isoforms (fPSA, cPSA and ratio of f/tPSA ratio) in diagnosing prostate cancer. An increase in the fPSA significantly lowered the risk of developing prostate cancer (OR 0.01, p=0.003). However, the ratio of f/tPSA was more predic- tive of the occurrence of prostate cancer. Total PSA and cPSA were not significant (p=0.753 and 0.237 respectively). The ratio PSA test was highly predictive (AUC= 0.921, p=0.002) than free PSA (AUC=0.908, p=0.003). The study conforms to other reports postulating that f/tPSA ratio can aid in the diagnosis of prostate cancer in the 3-10 ng/ml range as compared to the use of tPSA alone with f/ tPSA ratio being more predictive. The use of cPSA remains uncertain. Not withstanding resource limitations, there is a need for larger national cohort studies which may run concurrently with CaP awareness campaigns.

A Multicenter Study of [-2]Pro-Prostate Specific Antigen Combined With Prostate Specific Antigen and Free Prostate Specific Antigen for Prostate Cancer Detection in the 2.0 to 10.0 ng/ml Prostate Specific Antigen Range

Prostate specific antigen and free prostate specific antigen have limited specificity to detect clinically significant, curable prostate cancer, leading to unnecessary biopsy, and detection and treatment of some indolent tumors. Specificity to detect clinically significant prostate cancer may be improved by [-2]pro-prostate specific antigen. We evaluated [-2]pro-prostate specific antigen, free prostate specific antigen and prostate specific antigen using the formula, ([-2]pro-prostate specific antigen/free prostate specific antigen × prostate specific antigen(1/2)) to enhance specificity to detect overall and high grade prostate cancer. We enrolled 892 men with no history of prostate cancer, normal rectal examination, prostate specific antigen 2 to 10 ng/ml and 6-core or greater prostate biopsy in a prospective multi-institutional trial. We examined the relationship of serum prostate specific antigen, free-to-total prostate specific antigen and the prostate health index with biopsy results. Primary end points were specificity and AUC using the prostate health index to detect overall and Gleason 7 or greater prostate cancer on biopsy compared with those of free-to-total prostate specific antigen. In the 2 to 10 ng/ml prostate specific antigen range at 80% to 95% sensitivity the specificity and AUC (0.703) of the prostate health index exceeded those of prostate specific antigen and free-to-total prostate specific antigen. An increasing prostate health index was associated with a 4.7-fold increased risk of prostate cancer and a 1.61-fold increased risk of Gleason score greater than or equal to 4 + 3 = 7 disease on biopsy. The AUC of the index exceeded that of free-to-total prostate specific antigen (0.724 vs 0.670) to discriminate prostate cancer with Gleason 4 or greater + 3 from lower grade disease or negative biopsy. Prostate health index results were not associated with age and prostate volume. The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.

-2]Proenzyme Prostate Specific Antigen is More Accurate Than Total and Free Prostate Specific Antigen in Differentiating Prostate Cancer From Benign Disease in a Prospective Prostate Cancer Screening Study

Due to the limited specificity of prostate specific antigen for prostate cancer screening, there is an ongoing search for adjunctive biomarkers. Retrospective studies have suggested that an isoform of proenzyme prostate specific antigen called [-2]proenzyme prostate specific antigen may enhance the specificity of prostate specific antigen based screening. We examined the usefulness of this isoform in a prospective prostate cancer screening study. From a population of 2,034 men undergoing prostate cancer screening we examined the relationship between the measurement of the [-2]isoform of proenzyme prostate specific antigen (p2PSA) and prostate cancer detection. Specifically we compared the usefulness of total prostate specific antigen, the ratio of free-to-total prostate specific antigen, the ratio of p2PSA-to-free prostate specific antigen, and a formula combining prostate specific antigen, free prostate specific antigen and p2PSA (the Beckman Coulter prostate health index or phi) to predict prostate cancer in men from the study undergoing prostate biopsy with a prostate specific antigen of 2.5 to 10 ng/ml and nonsuspicious digital rectal examination. Despite similar total prostate specific antigen (p = 0.88), percent free prostate specific antigen (p = 0.02) and %p2PSA (p = 0.0006) distinguished between positive and negative biopsy results. On ROC analysis %p2PSA (AUC 0.76) outperformed prostate specific antigen (AUC 0.50) and percent free prostate specific antigen (AUC 0.68) for differentiating between prostate cancer and benign disease. Setting the sensitivity at 88.5%, p2PSA led to a substantial improvement in specificity as well as positive and negative predictive values. The Beckman Coulter prostate health index (AUC 0.77) had the best overall performance characteristics. This is the first prospective study to our knowledge to demonstrate that p2PSA provides improved discrimination between prostate cancer and benign disease in screened men with a prostate specific antigen of 2.5 to 10 ng/ml and a negative digital rectal examination.

Critical Appraisal of Prostate-specific Antigen in Prostate Cancer Screening: 20 Years Later

Prostate-specific antigen (PSA) is secreted by all types of prostate epithelial cells and has been used for 2 decades as a biologic marker for prostate cancer (PCa). Since the implementation of PSA screening in the United States, the detection of PCa has increased, accompanied by a decrease in the incidence of high-grade cancer and PCa-specific mortality rates. It has been suggested that these decreases have resulted from the enhanced detection of PCa while still curable. These data have been the impetus for early detection programs, which have recommended the initiation of screening as early as 40 years of age. Despite widespread use, PSA screening remains controversial, principally because of the lack of evidence from randomized controlled trials demonstrating a mortality benefit that could outweigh the concerns of the costs of overdiagnosis and overtreatment. Two ongoing, randomized controlled trials are examining whether screening reduces the risk of PCa-related mortality, and the results of these studies are expected soon. Although it has its limitations, PSA still remains the best-studied marker for the detection of PCa.

New Insights Into the Diagnostic Accuracy of Complexed and Total Prostate Specific Antigen Using Discordance Analysis Characteristics

Comparison of diagnostic performances of total and complexed prostate specific antigen (tPSA, cPSA) using ROC curve analysis resulted in controversial interpretations. To overcome the biases due to analysis of subgroups selected by concentration ranges of only 1 marker the novel approach named discordance analysis characteristics is presented. DAC method includes only patients who are discordantly categorized by the tests under investigation using cutoffs with identical sensitivity. Within those patients parameters describing diagnostic accuracy are calculated. The systematic nature of the results is confirmed by varying the cutoffs. DAC method is demonstrated considering the example of cPSA and tPSA data from 2 prostate cancer studies with a total of 1,624 patients (study A and B, of 283 and 565 with as well as 417 and 359 men without prostate cancer, respectively). PSA concentrations were measured using the Bayer assays. The DAC method proved that cPSA outperformed tPSA regarding the criteria diagnostic specificity and positive predictive value. Among discordantly tested patients cPSA detected patients with an about 2-fold higher risk to have prostate cancer and with a 3.6 to 5.5-fold better specificity than tPSA. Using cPSA instead of tPSA more than 10% of unnecessary biopsies could be avoided in the tPSA range of 3 to 5 ng/ml. The superior diagnostic performance of cPSA in comparison with tPSA warrants the recommendation to use cPSA as initial test in prostate cancer diagnostics. The DAC method is generally recommended to replace comparative ROC analyses of subgroups to evaluate the diagnostic usefulness of markers.

A Novel Serum Marker, Total Prostate Secretory Protein of 94 Amino Acids, Improves Prostate Cancer Detection and Helps Identify High Grade Cancers at Diagnosis

New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals. We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer. Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p <0.0001). The adjusted odds ratios for the presence of prostate cancer for patients with the lowest quartile of PSP94, compared to patients in the highest quartile was 2.70 (95% CI 1.8 - 4.0, p <0.0001). Among a subgroup of 649 men in whom PSA had a low predictive value (PSA less than 20 ng/ml, normal DRE and less than 70 years), 260 (40.1%) were found to have cancer. In this subgroup total PSP94 levels helped discriminate between patients with high grade disease (Gleason score 8 or more, median 1.90 ng/ml), moderate grade disease (Gleason score 7, median 2.34 ng/ml) and low grade disease (Gleason score 6 or less, median 2.60 ng/ml, p = 0.007). PSA and the FTPSA were not able to distinguish between patients with different grades in this group. Patients with low total PSP94 levels had a high probability for having prostate cancer detected at biopsy. The total PSP94 level was able to help identify patients with high grade disease among a subset of patients in whom PSA and FTPSA are least informative.

The Detection and Potential Economic Value of Complexed Prostate Specific Antigen as a First Line Test

Prostate cancer detection is subject to a number of variables that can lead to unnecessary biopsies and associated costs. Measuring cPSA has been proposed as an alternative to tPSA for the early detection of prostate cancer. Between November 1998 and April 2000, 1,362 men underwent transrectal ultrasound guided biopsies at 7 institutions. Of 1,243 evaluable men 467 with tPSA between 2.5 and 6.0 ng/ml, and normal digital rectal examination were analyzed. Statistical analysis used to compare cancer detection rates between PSA assays was performed using the Mann-Whitney U test. A separate group of 2,807 men who participated in a free cancer detection program was used to determine the current tPSA distribution and assess the economic impact of cPSA. Cancer was detected in 31.5% of the men (147 of 467) with tPSA between 2.5 and 6.0 ng/ml. Using a 2.2 ng/ml cPSA cutoff point detected 93.9% of cancers and would have avoided 20.3% of unnecessary biopsies in men with tPSA between 2.5 and 4.0 ng/ml. A 2.2 ng/ml cPSA cutoff point achieved an 11.9% overall decrease in the number of unnecessary biopsies in the tPSA range of 2.5 to 6.0 ng/ml with accompanying 98% sensitivity. The decrease in unnecessary biopsies is potentially associated with substantial health care cost savings. In the clinically relevant sensitivity ranges a 2.2 ng/ml cPSA cutoff point decreases the number of unnecessary biopsies and maintains higher specificity than a tPSA threshold of 2.5 ng/ml, illustrating the potential value of cPSA as a first line diagnostic test.

Comparison of the Clinical Value of Complexed PSA and Total PSA in the Discrimination between Benign Prostatic Hyperplasia and Prostate Cancer

Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. Results: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. Conclusions: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable.

Prostate Specific Antigen Isoforms and Human Glandular Kallikrein 2—Which Offers the Best Screening Performance in a Predominantly Black Population?

Free prostate specific antigen, complexed PSA and human glandular kallikrein 2 have independently been tested against the gold standard of total PSA for prostate cancer screening in largely white populations. With the incidence of prostate cancer much higher in black men, we sought to evaluate these markers simultaneously in a predominantly black population. A total of 138 men, of whom 108 were black, underwent ultrasound guided biopsy of the prostate for tPSA levels greater than 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn before biopsy and analyzed for tPSA, fPSA, cPSA and hK2 concentrations using standard methods (hK2 assay is for research use only, not for use in diagnostic procedures). The areas under the receiver operator characteristic curves were determined for each marker as well as biomarker combinations. Additionally, each parameter's specificity, positive and negative predictive values, and theoretical screening efficiency were assessed at or above the 95% sensitivity level. A total of 43 (31.1%) men had prostate cancer by biopsy. While the AUC for %fPSA was statistically the highest (0.822, p <0.001), cPSA offered the highest specificity (31.6%) and positive predictive power (31.7%) of any of the tested biomarkers at comparable sensitivity (greater than 95%). The calculated efficiency of cPSA (51.4%) was also higher than the other markers. Nearly 20% of biopsies would be avoided using cPSA vs standard tPSA screening methods. Comparing the major PSA isoforms and hK2, cPSA alone appears to offer superior diagnostic discrimination for cancer detection in a predominantly black population.

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume.

To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

PREDICTORS OF SUBSEQUENT PROSTATE CANCER IN MEN WITH A PROSTATE SPECIFIC ANTIGEN OF 2.6 TO 4.0 NG/ML AND AN INITIALLY NEGATIVE BIOPSY

Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.

Blood levels of free-PSA but not complex-PSA significantly correlates to prostate release of PSA in semen in young men, while blood levels of complex-PSA, but not free-PSA increase with age

The proportion of free- and complex-prostate specific antigen (PSA) in serum is used for differentiating between benign and malignant prostate disease. To further understand the physiological relationship between PSA in seminal plasma and blood, we have analyzed free-PSA (fPSA) and complex-PSA (cPSA) in blood and PSA in seminal plasma in young healthy men. We also compared age-related changes of PSA-forms in blood from young versus older men. Total-PSA (tPSA), fPSA, and cPSA were measured in (i) blood and semen from 289 male conscripts (mean age 18.1 years) and in (ii) blood from a representative population of 1,389 men (mean age 46.5 years) without diagnosis of prostate cancer (PCa) during long-term follow-up. fPSA in serum (r = 0.40, P < 0.0001) but not cPSA (r = 0.09, P = 0.11), correlates to PSA in seminal fluid. fPSA levels in blood in young (geometric mean: 0.20 ng/ml) versus middle-aged men (geometric mean: 0.18 ng/ml) was not different (P = 0.06), whereas cPSA in middle-aged men (geometric mean: 0.38 ng/ml) was higher (P < 0.0001) than in young men (geometric mean: 0.28 ng/ml). fPSA in blood, but not cPSA, is associated to PSA in semen ( approximately 17% co-variation). In blood cPSA, but not fPSA, increase with age in healthy men, which may reflect an increasing incidence of prostate disease.