Prostate-specific antigen (PSA) complexed to alpha1-antichymotrypsin improves prostate cancer detection using total PSA in Japanese patients with total PSA levels of 2.0-4.0 ng/mL

OBJECTIVE: To assess the utility of prostate-specific antigen (PSA) complexed to alpha1-antichymotrypsin (PSA-ACT) in prostate cancer screening in Japanese men with a total PSA level of 2.0-4.0 ng/mL, as improving cancer detection in men with these total PSA levels is a challenge for clinical urologists. PATIENTS AND METHODS: Total PSA and PSA-ACT were prospectively assessed and prostate biopsy recommended for patients who met either of two thresholds, i.e. a total PSA of > or = 2.0 ng/mL or a PSA-ACT of > or= 1.5 ng/mL. The diagnostic ability of total PSA and PSA-ACT, and free-to-total PSA ratio and prostate volume-adjusted density were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Of 1003 men enrolled, 547 met the biopsy criteria and a biopsy was taken in 315 (57.6%) patients. The area under the ROC curve for PSA-ACT (0.679) was significantly greater than that for total PSA (0.601, P = 0.04) and equivalent to that for the free-to-total ratio (0.686, P = 0.911) in 116 men, including 27 with cancer with total PSA levels of 2.0-4.0 ng/mL. PSA-ACT was more specific than the free-to-total ratio at a sensitivity of 95% (36% vs 18%, P < 0.05). The best variable for discriminating between cancer and benign disease in men with PSA levels of 2.0-4.0 ng/mL was PSA-ACT density (area under the curve 0.852) which provided 66% specificity at a sensitivity of 90%. CONCLUSIONS: PSA-ACT is better than total PSA and equivalent to the free-to-total ratio for detecting prostate cancer in men with PSA levels of 2.0-4.0 ng/mL, and is thus useful for reducing the number of unnecessary biopsies.     

Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUNDS: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.     

Prostate-specific antigen cut-off point of 2.5 ng/mL and increasing the number of prostate biopsies results in the detection of curable prostate cancer even in Japanese population

AIM: There is a trend for the cut-off point of Prostate-specific antigen (PSA) to be lower and the number of biopsies to be increased for detecting prostate cancer. I divided patients who visited my institution for prostate biopsy into 3 groups based on the time of examination. The results were evaluated retrospectively. METHODS: The three groups were: group A, PSA cut-off point of 4.0 ng/mL and sextant biopsy; group B, 2.5 ng/mL and 12 core biopsies; and group C, 2.5 ng/mL and saturation biopsy. I evaluated the rates of cancer detection, localized cancer, T1c, high grade cancer, major complications, insignificant cancer and the pain scores, and compared biopsy number and cancer detection rates with PSA range. Only the patients with T1c and PSA 2.6-10.0 ng/mL were evaluated about high grade cancer and insignificant cancer rates. RESULTS: Cancer detection rates, localized cancer rates and T1c rates were significantly high in group C. There were no significant differences in the high grade cancer rates, major complication rates and the insignificant cancer rates. A comparison between biopsy number and cancer detection rates was significantly high in the saturation biopsy group with PSA 4.1-10.0 ng/mL. CONCLUSION: A PSA cut-off point of 2.5 ng/mL and increasing the number of biopsies results in the increased detection of localized prostate cancer. The insignificant cancer rate, the high grade cancer rate and the complication rate were not significantly different among the groups. I recommend a PSA cut-off point of 2.5 ng/mL and an increased number of biopsies, saturation biopsy particularly in cases with PSA 4.1- 10.0 mg/mL.     

Clinical Evaluation of Serum Prostate-Specific Antigen-Alpha1 - Antichymotrypsin Complex Values in Diagnosis of Prostate Cancer: A Cooperative Study

Background We studied the clinical significance of serum prostate-specific antigen bound to α₁-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay.
Methods Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and y-seminoprotein (μgm- Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays.
Results Serum PSA-ACT values ranged from less than 0.10 to 1.4ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 1 55) averaged 3.4 ± 3.8ng/mL (mean ± SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8ng/mL for PSA-ACT, 7.2ng/mL for PSA, 3.8ng/mL for y-Sm, and 2.4ng/mL for thecomplexed/free PSA ratio of PSA-ACT/μtgM-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for γ-Sm, and 46% for the ratio between PSA-ACT/γ-Sm.
Conclusion Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.     

The significance of prostate-specific antigen alpha-1-antichymotrypsin complex and its indices for the detection of prostate cancer

We examined the usefulness of prostate specific antigen alph-1-antichymotrypsin complex (PSA-ACT) and its indices for the detection of prostate cancer in patients with a prostate specific antigen (PSA) level between 2.1 and 10.0 ng/ml. Between July 1999 and October 2001, 151 patients with a PSA level between 2.1 and 10.0 ng/ml underwent a systematic biopsy under transrectal ultrasound (TRUS) guidance. The clinical values of total PSA, PSA-ACT, PSA density (PSAD), PSA-ACT density (PSA-ACTD), PSA transition zone density (PSATZD) and PSA-ACT transition zone density (PSA-ACTTZD) for the detection of prostate cancer were compared by using receiver operating characteristic (ROC) curve analysis. Of the 151 patients, 36 (23.8%) were histologically confirmed as having prostate cancer. The differences between patients with prostate cancer and benign prostatic disease were significant with respect to the PSA and PSA-ACT related parameters examined in this study. According to ROC curve analysis, the area under the curve (AUC) of PSA-ACTTZD was the greatest of all the parameters. The differences was significant between the AUC of PSA-ACTTZD and total PSA (p < 0.05). The cutoff value of PSA-ACTTZD with 0.20 ng/ml2 showed the highest sum of sensivitity (90%) and specificity (55%). Also, in 86 patients with a PSA level between 2.1 and 6.0 ng/ml, the AUC of PSA-ACTTZD was the greatest of all the parameters. Measuring the level of PSA-ACT and its indices may provide a better differentiation of prostate cancer and benign prostatic disease than total PSA alone in patients with intermediate PSA levels. PSA-ACTTZD is the most useful indicator among PSA-ACT and its volume indices.     

Age-associated increase of prostate-specific antigen in a high level of men visiting urological clinics

OBJECTIVES: To evaluate the distribution of serum prostate-specific antigen (PSA) levels as a function of age in men with no evidence of prostate cancer who visited urological clinics. METHODS: Simultaneous measurements of total PSA and PSA-alpha-1-antichymotrypsin (PSA-ACT) were performed on patients who presented at urological clinics in Japan. After excluding 490 patients because of follow-up biopsy findings indicating prostate cancer, patients' history of prostatic surgery and medication affecting the serum PSA level, 1520 patients with PSA levels of less than 20.0 ng/mL were available for the study. RESULTS: Medians (95th percentile) of the total PSA levels were 0.9 (4.7), 1.2 (5.6), 1.7 (11.0), 2.1 (9.8) and 2.8 (11.0) ng/mL in men in their 40s (n = 37), 50s (n = 211), 60s (n = 488), 70s (n = 609) and 80s (n = 175), respectively, whereas those of PSA-ACT were 0.5 (2.9), 0.7 (3.7), 1.1 (7.4), 1.2 (5.9) and 1.6 (6.4) ng/mL, respectively. Both total PSA and PSA-ACT increase with aging, although comparison between the 10-year age groups showed a significant difference in the two molecular forms only between men in their 50s and 60s. CONCLUSIONS: The PSA ranges of men who visited urological clinics were higher than those of men participating in prostate cancer screening programs reported in other published studies. An age-associated increase in PSA similar to screening populations was also observed in urological outpatients. The results of the present study indicate that age-adjusted PSA cut-off levels can be used in outpatient settings, although the PSA reference value derived from the screening population should be carefully applied to symptomatic men of clinical practices.     

Value of prostate specific antigen α1-antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1–10.0ng/mL: Comparison with PSA-related parameters

BACKGROUND: The aim of the present study was to evaluate the usefulness of prostate specific antigen alpha1-antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. METHODS: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. RESULTS: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. CONCLUSIONS: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives.     

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.     

Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml

PURPOSE: In contemporary screening populations a major drawback of prostate specific antigen (PSA) is its relative lack of specificity, especially in the range of 4 to 10 ng/ml, where prostate cancer is found 25% of the time. ProPSA is a derivative of free PSA (fPSA) consisting of the truncated forms (eg [-2]proPSA, [-4]proPSA or the full-length [-7]proPSA). There is increasing evidence that proPSA is associated preferentially with prostate cancer. The objective of this study was to determine whether proPSA can influence the detection of early prostate cancer. MATERIALS AND METHODS: Archival serum samples obtained from 93 men who underwent a systematic 12-core prostate biopsy (total PSA range 4.0 to 10.0 ng/ml) were assayed for percent free PSA, total PSA and the 3 forms of proPSA (Hybritech Tandem Assays Beckman Coulter Access, Beckman Coulter, Inc., Brea, California). Free PSA, the cumulative sum of individual proPSA forms ([-2], [-4] and [-7], or sum-proPSA) and derivatives were determined. Of the 93 men assessed 41 (44%) had evidence of prostate cancer (76% Gleason 5/6, 19% Gleason 7 and 5% Gleason 8). Prostate volume was measured at systematic 12-core biopsy for the detection of prostate cancer. Results were analyzed using univariate and multivariate logistic regression (LR) nonparametric statistical methods. RESULTS: Using univariate LR, fPSA, percent fPSA (%fPSA), percent sum-proPSA and prostate volume significantly (p <0.05) differentiated men with prostate cancer from those with benign disease. However, applying stepwise backward multivariate LR, total PSA, %fPSA and sum-proPSA were retained and generated a receiver operator characteristic curve with an area under the curve of 76.6%. At 90% sensitivity these 3 variables collectively achieved a specificity of 44% for the detection of prostate cancer. Individually, the 3 retained variables had a specificity of 23% (total PSA), 33% (%fPSA) and 13% (sum-proPSA). CONCLUSIONS: Sum-proPSA, total PSA and %fPSA in combination improve the specificity of early prostate cancer detection in men with a total PSA of 4 to 10 ng/ml compared with the results of individual PSA molecular forms measured.     

Prostate-specific antigen adjusted for the transition zone volume as a second screening test: A prospective study of 248 cases

AIM: This study was conducted to verify the effectiveness of prostate-specific antigen adjusted for the transition zone volume (PSATZ), and its availability as a second screening test for prostate cancer detection. MATERIALS AND METHODS: Total prostate-specific antigen (PSA) and free PSA was measured in male patients who visited our outpatient department for voiding difficulty or screening for prostate cancer. Patients who had an intermediate PSA level between 4.0 and 10.0 ng/mL, with an apparently normal prostate on a digital rectal examination, were enrolled. PSATZ, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative patients (benign) were conducted. RESULTS: Of 248 patients, 51 (20.6%) had prostate cancer and 197 (79.4%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSAD, F/T ratio and PSATZ were 7.48 +/- 1.77 ng/mL, 0.23 +/- 0.09 ng/mL per mL, 0.14 +/- 0.08 and 0.71 +/- 0.44 ng/mL per mL in patients with prostate cancer and 6.59 +/- 1.60 ng/mL, 0.16 +/- 0.07 ng/mL per mL, 0.21 +/- 0.11 and 0.36 +/- 0.30 ng/mL per mL in patients with benign, respectively. Receiver operating characteristics (ROC) curve analysis demonstrated that PSATZ predicted the biopsy outcome better than F/T ratio. With a cut-off value of 0.37 ng/mL per mL, PSATZ had a sensitivity of 74.5% and a specificity of 72.6% for predicting prostate cancer. The maximal cut-off value that preserves 100% of sensitivity was 0.2, and at this cut-off value, 16.1% of unnecessary biopsies could be reduced. CONCLUSIONS: Prostate-specific antigen adjusted for the transition zone volume may be more useful than other strategies in detecting prostate cancer in patients with intermediate PSA levels of 4.0-10.0 ng/mL. It can be used as a second screening test to reduce unnecessary biopsy.     

Prostate cancer detection among men with prostate specific antigen levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population

PURPOSE: Prostate cancer detection at levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population has not been elucidated. The purpose of this study is to investigate the cancer detection rate and clinical relevance of prostate cancer in this PSA range. MATERIALS AND METHODS: All urological patients 70 years or younger tested for prostate cancer were studied. There were 550, 97, 112 and 52 patients with a PSA of less than 2.5, 2.5 to 4.0, 4.1 to 10.0 and more than 10.0 ng/ml, respectively. Transrectal 10-core prostate biopsy was performed in 80 (82%) of the 97 patients with a PSA of 2.5 to 4.0 ng/ml and 102 (91%) of the 112 patients with a PSA of 4.1 to 10.0 ng/ml. RESULTS: Cancer detection rates in patients who underwent biopsy were 26.3% and 34.3% at PSA levels 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. High grade cancers with Gleason score 7 or more were found in 19.0% and 22.9% of patients with cancer with PSA 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. No significant difference was found between the 2 groups in pathological findings on biopsy, including percent positive cores (16.7% vs 20.0%, p = 0.10), maximum cancer length (25.0% vs 30.0%, p = 0.28) and maximum percent cancer length (2.0 vs 3.0 mm, p = 0.17). CONCLUSIONS: Japanese urological referral patients develop prostate cancer quite commonly even if their serum PSA levels are 2.5 to 4.0 ng/ml. Since these cancer cases include high grade, clinically significant cancer, prostate biopsy might be considered at least for selected cases in this PSA range.     

Diagnostic significance of PSA density adjusted by transition zone volume in males with PSA levels between 2 and 4ng/ml

OBJECTIVE: To investigate the diagnostic significance of prostate-specific antigen (PSA), density (PSAD), and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.1 and 4.0ng/ml. METHODS: Between 1993 and 2000, 69 men with PSA levels between 2.1 and 4.0ng/ml underwent transrectal ultrasonography (TRUS) and 8-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml. RESULTS: The detection rate of prostate cancer was 21.7% (15/69). The percentage of patients with extracapsular disease was 33.3% (5/15) and primary Gleason grade 4 or 5 was obtained in 4 (26.7%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml, respectively. CONCLUSIONS: The use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.1 to 4.0ng/ml.     

Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

Prostate-specific antigen adjusted for the transition zone volume versus free-to-total prostate-specific antigen ratio in predicting prostate cancer

BACKGROUND: We performed this study to assess the efficacy of prostate-specific antigen adjusted for the transition zone volume (PSATZ) and free-to-total prostate-specific antigen (PSA) ratio (F/T ratio) in predicting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasonography guided systemic sextant biopsies and had a PSA of 4.1-10.0 ng/mL. PSATZ was compared with F/T ratio via receiver operating characteristic (ROC) curves. RESULTS: Of 67 patients, 22 (32.8%) had prostate cancer and 45 (67.2%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSA density, F/T ratio and PSATZ were 7.96+/-2.01ng/mL, 0.28+/-0.14 ng/mL/cc, 0.10+/-0.06 and 0.70+/-0.28 ng/mL/cc in patients with prostate cancer and 6.39+/-1.68 ng/mL, 0.16+/-0.06 ng/mL/cc, 0.15+/-0.05 and 0.29+/-0.10 ng/mL/cc in patients with BPH, respectively. The ROC curve analysis demonstrated that PSATZ predicted the biopsy outcome significantly better than F/T ratio in all 67 patients (P<0.01) and in a subset of 53 men with normal digital rectal examination (P<0.01). With a cut-off value of 0.35 ng/mL/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ and F/T ratio may be useful in diagnosing prostate cancer with intermediate levels of PSA. Prostate-specific antigen adjusted for the transition zone volume is more accurate than F/T ratio in distinguishing benign prostatic disease from prostate cancer. But large prospective studies are required to assess the precise role of PSATZ and F/T ratio in early prostate cancer detection.     

Comparative analysis of complexed prostate specific antigen, free prostate specific antigen and their ratio in detecting prostate cancer

PURPOSE: We evaluate the diagnostic use of total, free and complexed serum prostate specific antigen (PSA), and their ratios for enhancing the specificity in detecting prostate cancer. MATERIALS AND METHODS: A total of 354 nonconsecutive men undergoing prostate biopsy were eligible for this retrospective and prospective study. Cancer was found in 122 of these 354 men (34%). Receiver operating characteristics curve analyses were used to calculate and compare the performance of total PSA (Hybritech, San Diego California and Bayer, Tarrytown, New York), complexed PSA (Bayer), percent complexed PSA and percent free PSA. In addition, sensitivity and specificity were calculated and compared. RESULTS: The area under the receiver operating characteristics curve was highest for percent free PSA, followed by percent complexed PSA, complexed PSA and the 2 total PSA assays (Hybritech and Bayer). The cutoff value of 3.45 ng./ml. for complexed PSA detected the same number of cancers and resulted in 1 additional false-positive case compared with a Hybritech total PSA threshold of 4.0 ng./ml. At sensitivities of 80% to 95%, there were no significant differences for detection comparing the corresponding specificities between Hybritech total PSA and complexed PSA for all 354 men. Complexed PSA alone did not enhance the overall diagnostic accuracy compared with percent free PSA in the Hybritech total PSA range between 4.01 and 6.00 ng./ml., between 6.01 and 10.00 ng./ml., and between 2.50 and 6.00 ng./ml. At sensitivities of 80% to 95% specificity of percent complexed PSA was almost identical to that of percent free PSA except for the Hybritech total PSA range less than or equal to 4.00 ng./ml. CONCLUSIONS: This study suggests complexed PSA is equivalent to total PSA for the early detection of prostate cancer. Percent free PSA outperforms complexed PSA and percent complexed PSA performed equivalently to percent free PSA in all total PSA ranges analyzed between 2.5 and 10 ng./ml.     

Lower urinary tract symptoms and risk of prostate cancer in Japanese men

Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. A total of 3511 men aged 50-79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0-7 and 8-35. Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8-35 was significantly higher than that in the 0-7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group.     

Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL

Objectives. To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool.Methods. One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone.Results. Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies.Conclusions. A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate.     

Ratio of prostate specific antigen minor molecular forms-to-total prostate specific antigen is constant regardless of the pathological condition of the prostate

PURPOSE: We assessed 3 molecular forms of prostate specific antigen (PSA) prospectively to determine the real proportion of the nonfree, nonalpha1-antichymotrypsin complex form of PSA-to-total PSA and evaluated the clinical significance of its various forms. MATERIALS AND METHODS: We prospectively assessed 1,878 serum samples from 994 subjects for total PSA, free PSA and PSA-alpha1-antichymotrypsin complex (ACT). Nonfree, nonPSA-ACT PSA (minor form PSA) was calculated as the difference between total PSA and the sum of free PSA plus PSA-ACT complex. RESULTS: The proportion of the minor form PSA was approximately 20% to 25% of total PSA at any range of total PSA, whereas that of free PSA and PSA-ACT decreased and increased, respectively, in correlation with the increment of total PSA. There was no significant difference in the percent of minor form PSA in patients with prostatic carcinoma and those with benign prostatic status. The proportion of minor form PSA was constant, while the percent of free PSA and PSA-ACT increased and decreased, respectively, in accordance with total PSA regression after hormonal therapy for prostatic carcinoma. PSA-ACT was judged to be superior to total PSA for distinguishing prostatic carcinoma in men with PSA 2 to 10 ng./ml. by ROC analysis. CONCLUSIONS: Approximately a fourth of total PSA consists of minor forms of complexed PSA. The average proportion of minor form-to-total PSA was constant at various levels of total PSA and at any prostatic status of patients. PSA-ACT was superior to total PSA for the early detection of prostatic carcinoma.     

Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL

Aim： To investigate whether the measurement of serum zinc may improve the detection of prostate cancer （PCa） in men who had total prostate-specific antigen （PSA） levels higher than 4.1 ng/mL. Methods： A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men （4.8 %） with elevated PSA, 143 （3.6 %） underwent a transrectal ultrasonography （TRUS）-guided biopsy of the prostate, and 42 men （1% of total and 29.3 % of men undergoing biopsy） were found to have cancer. The areas under the receiver operating characteristic curves （ROC-AUC） were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio （fit）. Results： The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios（OR） of 5.0. A cutoff value of 100 gg/mL for-serum zinc concentration provided a sensitivity of 90.5 % and a specificity of 32.7 % in elevated PSA range, and a sensitivity of 93.3 % and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0 % higher than 62.7 % of f/t PSA ratio and 56.7 % of total PSA. Conclusion： PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA. （Asian J Androl 2005 Sep; 7： 323-328）