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.     

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.     

游离前列腺特异抗原百分比/前列腺特异抗原密度在前列腺癌诊断中的应用

目的探讨游离前列腺特异抗原百分比（FPSA／TPSA值）／前列腺特异抗原密度[（F／T）／PSAD值]在前列腺癌诊断中的意义。方法回顾分析204例行经直肠超声引导前列腺穿刺活检患者的诊断资料,其中前列腺癌90例、良性前列腺增生114例,分析总PSA（TPSA）、FPSA／TPSA值、PSAD、（F／T）／PSAD值等指标在判断前列腺癌的敏感性为90％时的截点及相应的特异性。结果不同血清PSA水平（〈4．0,4．0～,10．1～和〉20．0μg／L）的前列腺癌患者的（F／T）／PSAD值与良性前列腺增生患者比较,差异有统计学意义（P〈0．05）;前列腺癌患者的（F／T）／PSAD值低于良性前列腺增生患者;（F／T）／PSAD值比FPSA／TPSA值和PSAD更有助于提高诊断特异性,在敏感性为90％左右的前提下,FPSA／TPSA值的特异性为31．6％,PSAD的特异性为45．6％,（F／T）／PSAD值的特异性为64．0％;PSA水平不同,取的（F／T）／PSAD值截点也不同：PSA〈4．0μg/L时截点为2．5,PSA为4．0～20．0μg／L时截点为0．8;PSA〉20．0μg／L时截点为0．5。结论应用（F／T）／PSAD值能够在保持较高敏感性的前提下,显著提高前列腺癌诊断的特异性。     

The potential role of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the detection of prostate cancer

Aim:   Two-thirds of patients with a gray-zone prostate-specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity.
Methods:   During the period April 2004 through March 2006, 185 patients with a PSA level of 4.0–10.0 ng/mL underwent MR imaging and transrectal ultrasonography-guided 8-core biopsy (systemic sextant biopsy of the peripheral zone plus two cores of transition zone). All MR images were interpreted prospectively by two radiologists. An image was considered positive for prostate cancer if any feature indicated a cancerous lesion. Receiver operating characteristic (ROC) curves were used to compare the usefulness of the PSA level, PSAD and PSA transitional zone density (PSATZ) for the detection of prostate cancer.
Results:   Of the 185 patients, 62 had prostate cancer. Sensitivity and specificity of the axial T2-weighted MR imaging findings for cancer detection were 79.0% and 59.4%, respectively. The area under the ROC curve was 0.590 for the PSA level, 0.718 for PSAD and 0.695 for PSATZ. MR imaging findings and PSAD were shown by multivariate analysis to be statistically significant independent predictors of prostate cancer ( P  < 0.001). With a PSAD cut-off value of 0.111, sensitivity was 96.8%, but specificity was 19.5%. Combining MR imaging findings with PSAD increased the specificity to 40% and retained 95% sensitivity.
Conclusion:   MR imaging findings combined with PSAD provide high sensitivity and improve the specificity for the early detection of prostate cancer.     

前列腺特异性抗原密度的测定在诊断前列腺癌中的价值

对１０例非转移性前列腺癌和２０例前列腺增生的前列腺特异性抗原密度（ＰＳＡＤ）进行研究。前列腺癌平均ＰＳＡＤ值为０．７１１，而前列腺增生为０．０７５；两者有极显著性差异（Ｐ＜０．００１）。９例ＰＳＡＤ＞０．２者，８例为前列腺癌。１６例ＰＳＡＤ＜０．１者，无１例前列腺癌。８例前列腺癌患者中有３例前列腺特异性抗原（ＰＳＡ）＜１０ｎｇ／ｍｌ，１例＜２．８ｎｇ／ｍｌ。１６例前列腺增生患者中７例ＰＳＡ＞２．８ｎｇ／ｍｌ，３例＞１０ｎｇ／ｍｌ。表明血清ＰＳＡ轻中度增高或正常时，ＰＳＡＤ可作为前列腺癌早期筛选诊断的有效指标之一。     

Prostate cancer detection by prostate-specific antigen-related parameters

Total serum prostate-specific antigen (PSA) levels, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were compared to clarify the clinical significance of these parameters in the diagnosis of prostate cancer (CaP) with intermediate PSA concentrations (4-10 ng/ml). PSAD and F/T ratio were obtained during the period from May 1999 to April 2001 from 43 patients with serum PSA concentrations of 4-10 ng/ml who underwent ultrasound-guided systematic sextant biopsies. PSAD was compared with total serum PSA and F/T ratio via receiver operating characteristic (ROC) curves for diagnosis of CaP. Diagnosis of CaP and non-CaP was made in 12 (27.9%) and 31 (72.1%) of the 43 patients, respectively. Mean serum PSA, PSA density and F/T ratio were 7.308 +/- 0.636 ng/ml, 0.271 +/- 0.039 ng/ml/cm3 and 16.225 +/- 4.911% in patients with CaP and 6.300 +/- 0.289 ng/ml, 0.178 +/- 0.020 ng/ml/cm3 and 15.213 +/- 0.980% in those with non-CaP, respectively. The ROC curve analysis demonstrated that PSAD predicted the biopsy outcome significantly better than F/T ratio and total PSA in all 43 patients (p < 0.05). In distinguishing CaP patients, the cutoff value of 0.16 ng/ml/cm3 for PSAD yielded a specificity level of 71.0% at a sensitivity level of 83.3%. Our study revealed that PSAD is a significant predictor in distinguishing CaP from non-CaP in Japanese men.     

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.     

前列腺特异抗原水平为4～10 μg/L的前列腺癌诊断对策

目的评价现有的前列腺特异抗原(PSA)修正方法对PSA在4~10μg/L的前列腺癌的诊断价值。方法选取经直肠B超引导下前列腺多点穿刺活检血PSA测值在4~10μg/L的86例患者,分析其PSAD、PSATZ、F/T比值及PSA修正方法各域值范围内,对前列腺癌诊断的敏感度及特异度。结果PSAD、PSATZ和F/T比值在各域值范围内,对诊断前列腺癌的敏感度均未超过50%,将PSAD域值设为0.18μg/L/cc时有较高的敏感度,F/T比值设为0.25时有较高的特异度,而PSATZ在各域值范围内对前列腺癌的敏感度及特异度无显著优势。结论PSA修正方法不能有效提高国人血PSA4~10μg/L的前列腺癌检出率;当PSAD超过0.18μg/L应建议患者作前列腺穿刺活检,F/T比值小于0.25则应增加穿刺点。     

The significance of TPSA, free to total PSA ratio and PSA density in prostate carcinoma diagnostics

Prostate-specific antigen (PSA) is the one of the most valuable tumor markers for the early detection and management of prostate carcinoma, but not an ideal one because of poor specificity in the case of prostatic hypertrophy and other benign conditions. In order to overcome this drawback some other parameters as is free to total ratio (F/T) PSA and PSA density (PSAD) are introduced. It has been investigated in 60 patients, 18 of them are proved to be found prostate cancer and other 42 were identified as benign prostatic hyperplasia. Patients with CaP had TPSA median of 11.4 ng/ml and the others with benign prostatic hyperplasia (BPH) had 6.9 ng/ml. In these two groups there was statistical significant difference (p 0.01). By receiver operating characteristics curve (ROC) estimated cutoff for TPSA was 4.0 ng/ml with 95% sensitivity, 30% specificity and area covered by ROC was in amount of 0.76. Median F/T ratio for patients with prostate cancer was 0.10, and for benign prostatic hyperplasia patients it was 0.25. For these values there is also statistical difference (p). Using ROC cutoff for F/T PSA was determined at the value of 0.18 with sensitivity 95%, specificity 80% and area under the curve (AUC) 0.93. Median for PSAD in the group with CaP was 0.38 and in the BPH group was 0.16. There was statistical significance within those two groups. In conclusion F/T PSA, PSAD and TPSA are valuable tumor markers in distinguishing patients with CaP ant those without with modestly raised TPSA. Also F/T PSA showed up as better marker than TPSA and PSAD in investigated group of patients.     

Prostatic volume and volume-adjusted prostate-specific antigen as predictive parameters for T1c prostate cancer

We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels.     

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.     

Utility of prostate specific antigen doubling time in repeat biopsy for prostate cancer

PURPOSE: It is not rare that the repeat biopsy is performed when the initial biopsy was negative. However, there is not a clear indication for the repeat biopsy. We evaluated the utility of prostate specific antigen doubling time (PSA-DT) as indication for the repeat biopsy. MATERIALS AND METHODS: Of men 103 underwent repeat biopsy after initial negative prostate biopsy, 55 men who had three or more serial PSA measurements until repeat biopsy were evaluated. PSA-DT was calculated using a log-linear regression model and compared with other PSA-related parameters. RESULTS: Prostate cancer was diagnosed in 22 patients (40.0%). Mean PSA-DT in 55 patients was 59.3 months. Comparing of repeat positive biopsy group and negative group, PSA density (PSAD) and PSA velocity (PSAV) in the positive biopsy group were significantly greater than in the negative biopsy group. Age, serum PSA concentration at initial and repeat biopsy, PSA adjusted for volume of transition zone (PSATZ), free to total PSA ratio (%F/T) did not recognize significant differences between both biopsy groups. PSA-DT of positive biopsy group (35.1 months) was significantly shorter than that of negative biopsy group (76.5 months). None was diagnosed prostate cancer whose PSA-DT was longer than 96 months. CONCLUSION: When we considered prostate repeat biopsy, it was thought that PSA-DT could be one important material, but it was limitation for indication as to other PSA-related parameters.     

Using multiple cutpoints for the free-to-total prostate specific antigen ratio improves the accuracy of prostate cancer detection

BACKGROUND: Using a single cutpoint for the free-to-total (F/T) prostate specific antigen (PSA) ratio loses important diagnostic information. We evaluated the performance of multiple F/T PSA cutpoints in detecting prostate cancer in men with nonspecific PSA values. METHODS: We extracted sensitivity and specificity data from 12 studies reporting on >or=30 cancer patients with PSA values between 2.0 and 10.0 ng/mL. We calculated stratum-specific likelihood ratios (LR) and areas under the receiver operating characteristic (ROC) curves. RESULTS: Multiple cutpoints for the F/T PSA ratio significantly increased the area under the ROC (0.70) compared with the single investigator-selected cutpoint (0.62), P < 0.004. The LR for the most positive cutpoint stratum (2.62) was significantly higher than the LR for a positive test from the single cutpoint (1.36), P < 0.004. CONCLUSIONS: Using multiple cutpoints increased the discriminating power of the F/T PSA ratio and led to greater probability revisions in the most positive test-result strata.     

Prostatic volume and volume-adjusted prostate-specific antigen as predictive parameters for prostate cancer patients with intermediate PSA levels

The object of the study was to examine the usefulness of volume-adjusted prostate-specific antigen (PSA) parameters for prediction of prostate cancer in the patients with intermediate PSA levels. The subjects were 235 patients with intermediate PSA levels (range: 4.1-10.0 ng/ml) whose prostate volume (PV) and prostate transition zone volume (TZV) were evaluated between August 1996 and April 2004. PSA, PV, TZV, PSA density (PSAD) (PSA/PV) and PSA transition zone density (PSATZD) (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and multivariate logistic regression analyses were used to analyze the odds ratios of age, PSA, PSAD, PSATZD, PV, TZV, digital rectal examination (DRE) and transrectal ultrasonography (TRUS) findings. Fifty-five patients (23.4%) of 235 patients had biopsy-proven prostate cancer. The univariate analysis revealed significant differences in the mean values of age, PSAD, PSATZD, PV, TZV and DRE between the patients with cancer and the non-cancer patients. The ROC curve analysis revealed that PV, TZV, PSAD and PSATZD had significant predictive values as compared with that of PSA. However, there was no difference in AUC between them. The stepwise logistic regression analysis showed that the age, PV, PSATZD and DRE had significant predictive values, and that PSATZD had the most predictive power. In conclusion, both PSAD and PSATZD had significant predictive values in discriminating prostate cancer. Furthermore, the stepwise logistic regression analysis showed that PSATZD had the strongest predictive value.     

Evaluation of prostate specific antigen (PSA) adjusted to transition zone in prostatic cancer detection

ObjectiveTo investigate if PSA adjusted to transition zone (PSA-TZ) can be considered as a predictor parameter of cancer with better specificity or not than PSA, PSA density (PSAD) or PSA free/total ratio.Material and methodsData of 706 patients with sextant prostatic biopsies are analyzed in prospective way because of prostatic cancer suspicion. Range of PSA was between 4 to 20 ng/ml. Determination of PSA-TZ was calculated by dividing the PSA value by the volume of the transition zone of the prostate applying the ellipsoid formula and comparison of obtained results in detection of cancer was performed by ROC curves analysis for each one of PSA-related parameters.ResultsOf the total group of patients, in 199 cases (28.2%) prostatic cancer was detected. Analysis by ROC curves demonstrated than PSA-TZ and PSAD were better predictors of cancer than PSA free/total ratio and PSA (p<0.0001). The cutoff value of PSA-TZ of 0.18 ng/ml/cc was considered as the best, obtaining a 95% sensitivity and a 27% specificity. For this sensitivity, PSA, PSAD and PSA free/total ratio only obtained 5, 9 and 16% specificity respectively. Areas under curve (AUC) obtained for PSA, PSA free/total ratio, PSAD and PSA-TZ were 0.539, 0.612, 0.694 and 0.722 respectively.ConclusionsPSA-TZ in the studied population was a parameter with better diagnostic specificity than PSA, PSAD and PSA free/total ratio for the same 95% sensitivity. This would justify its utility in clinical paractice reducing the number of unnecesary biopsies.     

Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.     

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.     

The value of γ-seminoprotein in combination with prostate specific antigen in detecting prostate cancer

BACKGROUND: The present study was undertaken to investigate the value of gamma-seminoprotein (gamma-Sm) and the gamma-Sm/prostate specific antigen (PSA) ratio in combination with serum PSA in detecting prostate cancer. METHODS: Prostate specific antigen, gamma-Sm and the gamma-Sm/PSA ratio were evaluated in 112 patients with untreated prostate cancer and 90 patients without prostate cancer who had serum PSA and gamma-Sm levels above their respective detection limits. RESULTS: When data for all of the patients were analyzed, serum PSA and gamma-Sm levels were significantly higher and the gamma-Sm/PSA ratio was significantly lower in patients with prostate cancer than patients without prostate cancer. The serum PSA and gamma-Sm levels significantly increased and the gamma-Sm/PSA ratio significantly decreased with advancing clinical stage in patients with prostate cancer. Among the patients with serum PSA levels ranging from 1.8 to 6 ng/mL, the gamma-Sm/PSA ratio was significantly lower (P < 0.05) and gamma-Sm levels were lower (P = 0.054) in the patients with prostate cancer than in those without prostate cancer, but serum PSA levels were not significantly different (P = 0.53). A receiver operating characteristic (ROC) analysis demonstrated that the areas under the ROC curves were 0.54 for PSA, 0.65 for gamma-Sm and 0.69 for the gamma-Sm/PSA ratio for prediction of prostate cancer in the PSA range from 1.8 to 6 ng/mL, although the ROC analysis suggested that the gamma-Sm/PSA ratio does not provide significant advantage over PSA in detecting prostate cancer when all of the patients were analyzed. CONCLUSIONS: These results suggest that the gamma-Sm/PSA ratio and gamma-Sm may facilitate differentiation between patients with and without prostate cancer who have intermediate PSA levels.     

Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters

BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.     

Measurement of prostate specific antigen complexed to α1-antichymotrypsin to avoid unnecessary biopsy in patients with serum prostate specific antigen levels 4–20 ng/mL

AIM: To investigate whether measuring prostate specific antigen complexed to alpha1-Antichymotrypsin (PSA-ACT) can increase sensitivity and specificity in detecting prostate cancer. METHODS: In this prospective study, we measured serum total PSA, PSA-ACT, free PSA, prostate volume and transition zone volume on 210 patients with total PSA level of 4-20 ng/mL. From fitted curves between positive predictive values for prostate cancer and age, prostate volume, transition zone volume, total PSA, PSA-ACT or F/T ratio, each function predicting prostate cancer was determined. Relative probabilities for prostate cancer (RPpca) which were defined by combined functions of age, F/T ratio, prostate volume or transition zone volume, and total PSA or PSA-ACT were calculated. Furthermore, using logistic regression, analysis was performed to determine the probability of prostate cancer. Receiver-operating characteristic analysis was performed to clarify the areas under the curve (AUC) for conventional single parameters, RPpca and logistic regression probability. RESULTS: F/T ratio showed the largest AUC among conventional parameters. The AUC of RPpca was larger than those of F/T ratio and logistic regression probability. RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio showed the largest AUC and highest specificity at sensitivity 95% level, however, specificities at sensitivity 90% and 85% were identical to those of RPpca using the functions of age, prostate volume, total PSA and F/T ratio. CONCLUSIONS: RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio was the best way to detect prostate cancer, however, the usefulness of PSA-ACT appears limited, considering the cost.