总体和自由型前列腺特异抗原指数在日本人群前列腺癌筛选中的价值和局限性(英文)

目的:在日本某单机构中评定前列腺特异抗原指数(f/tPSA)的价值和局限性,重点在于避免无意义的前列腺组织活检。方法:631名年龄在44-93岁之间(平均年龄69.8岁)的男性,在日本新滹中心医院用能量多普勒超声波图像引导的经直肠10-点前列腺组织活检后发现其 PSA 值增加,用总体前列腺特异抗原 (tPSA)和前列腺特异抗原指数(f/tPSA)观察组织学特征。结果:在134名 tPSA 为26 ng/mL 或更高病人中,126人(94.3%)检测到前列腺癌(PCa),tPSA 为21-25 ng/mL 时的 PCa 检出率是59.4%,16-20 ng/mL 时为39.2%,11-15 ng/mL 时为30.0%,4.1-10 ng/mL 时为20.0%,小于等于4.0 ng/mL 时为7.6%。在任何一个 tPSA 值区间,PCa 组的 f/tPSA 值都明显低于非肿瘤组(平均为0.122vs.0.160,P<0.001)。接收器特性法表明,对于 tPSA 值在3.0-10 ng/mL(P<0.01)之间的病人,f/tPSA(AUC:0.664)比 tPSA(AUC:0.559)更有价值。虽然以 f/tPSA 等于0.250为分界点可能产生1.8%的 PCa 漏诊率,但是这样有可能节约9.2%不必要的组织活检。结论:对预测 PCa 发病率,f/tPSA 比单独的 tPSA 更有价值。因此,对于被称为 tPSA 灰色地带的亚洲男性来说,我们推荐在 PCa 筛查中用0.250作为 f/tPSA分界点。     

Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6-4.0 ng/mL range of total PSA

OBJECTIVE: To compare the performance of complexed prostate-specific antigen (cPSA) to total PSA (tPSA) and percentage free PSA (f/tPSA) in the diagnosis of prostate cancer for the tPSA range 2.6-4.0 ng/mL. PATIENTS AND METHODS: Consecutive men scheduled for prostate biopsy were enrolled prospectively at 14 different sites in two multicentre studies in Europe and the USA. Serum obtained before biopsy was tested with the ACS:180 and Immuno 1 tPSA and cPSA assays (Bayer Diagnostics, Tarrytown, NY, USA) and the Access fPSA and tPSA assays (Beckman, Inc., San Diego, CA, USA). Receiver operating characteristics (ROC) curves were generated to compare the diagnostic performance of tPSA, cPSA and f/tPSA. RESULTS: Of 316 men with a tPSA of 2.6-4.0 ng/mL, 82 (26%) were diagnosed with prostate cancer on biopsy. ROC analysis of all 316 men showed an area under the curve (AUC) for cPSA of 0.63, significantly greater than the AUC for tPSA of 0.56 (P = 0.008). At a sensitivity of 95%, threshold values of 2.3 ng/mL for cPSA and 2.73 ng/mL for tPSA provided specificities of 20.1% and 9.8%, respectively. f/tPSA was only available for 205 of the 316 (65%) men and the AUC for cPSA was 0.63, and did not significantly differ from the f/tPSA AUC of 0.64 (P = 0.58). CONCLUSIONS: As a single test, cPSA provides improved specificity over tPSA and comparable specificity to f/tPSA for detecting prostate cancer, and may reduce the number of unnecessary prostate biopsies in the 2.6-4.0 ng/mL tPSA range.     

The influence of prostate volume on the prostate-specific antigen (PSA) level adjusted for the transition zone volume and free-to-total PSA ratio: a prospective study

OBJECTIVES: To evaluate the influence of prostate volume on the prostate-specific antigen (PSA) level adjusted for the transition zone volume (PSAT) and free-to-total PSA ratio (f/tPSA) in detecting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From March 1997 to June 1999, the f/tPSA and PSAT were measured in 105 patients who underwent ultrasound-guided systemic biopsies and had a PSA level of 4.1-10.0 ng/mL, with an apparently normal prostate on a digital rectal examination. The PSAT and f/tPSA were evaluated in all patients and in subgroups of patients with small (< 40 mL) or large (> or = 40 mL) prostates, using receiver operating characteristic (ROC) curves. RESULTS: Total prostate volume was highly correlated with transition zone volume in all patients and in both subgroups (P < 0.001). In all 105 patients, PSAT had a sensitivity of 82% and its use would have avoided the largest number of unnecessary biopsies (87% specificity) at a threshold value of 0.35 ng. In men with small prostates f/tPSA and PSAT had a high sensitivity and specificity, at threshold values of 0.12 and 0.35 ng, respectively. In large prostates the PSAT was superior to f/tPSA in detecting prostate cancer. CONCLUSIONS: These results suggest that both f/tPSA and PSAT are useful in detecting prostate cancer in men with small prostates, while PSAT is superior to f/tPSA in detecting prostate cancer in men with large prostates.     

Variation in percentage-free prostate-specific antigen (PSA) with prostate volume, age and total PSA level

OBJECTIVE: To examine the correlation between prostate volume, patient age and total prostate-specific antigen (tPSA) with the percentage-free PSA (f/tPSA) in a population-based cohort of men with no prostate cancer and with a tPSA of < 10.0 ng/mL. SUBJECTS AND METHODS: Men who in 1988-1989, after randomized selection in the general population, participated in a population-based screening study for prostate cancer, were investigated. In all, 1622 of the men (aged 55-70 years) were considered free from prostate cancer and had a tPSA level of < 10.0 ng/mL. The f/tPSA and tPSA were determined in frozen sera from each individual, and related to prostate volume and age measured at the time of the study. The entire population was investigated, as were four subpopulations based on tPSA levels (< 2.0, 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL). Statistical calculations included multiple regression and correlation analysis. RESULTS: The f/tPSA level varied with prostate volume and age, but the decisive factor for this variation was the tPSA level. The closest correlation was in the tPSA interval 7.0-9.9 ng/mL, where volume and age together explained 47% of the variation in f/tPSA. Also, for men with tPSA levels in each of the intervals 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL, the f/tPSA increased with higher prostate volumes and age. In men with tPSA levels of < 2.0 ng/mL the f/tPSA was not affected by variations in prostate volume or age. CONCLUSION: The variation in f/tPSA with prostate volume, age and tPSA is highly dependent on the tPSA level. Volume and age in the tPSA interval 7.0-9.9 ng/mL can explain almost half the variation in f/tPSA, whereas this influence is insignificant in men with a tPSA of < 2.0 ng/mL.     

fPSA/tPSA比值优化前列腺癌早期诊断作用的研究

目的 :探讨游离前列腺特异性抗原 /总前列腺特异性抗原 (fPSA/tPSA)比值在优化tPSA早期诊断前列腺癌(PCa)中的作用。　方法 :以长春市 5 0岁以上PCa集团普查中tPSA在 4 .0～ 2 0 .0 μg/L范围、并接受前列腺活检的1 87例受检者为研究对象 ,测定tPSA、fPSA含量 ,应用SPSS 1 0 .0软件对不同区间fPSA/tPSA比值进行统计学分析。结果 :①tPSA在 4 .0～ 1 0 .0 μg/L、1 0 .0～ 2 0 .0 μg/L区间时 ,PCa检出率分别为1 8.1 %、2 2 .5 %。②ROC曲线分析显示不同区间时fPSA/tPSA比值的曲线下面积 (AUC)均大于tPSA (P <0 .0 5 )。③fPSA/tPSA比值取 0 .2 5为界值时 ,tPSA在 4 .0～ 1 0 .0 μg/L、1 0 .0～ 2 0 .0 μg/L两区间诊断PCa的敏感度分别为90 .5 %和 87.5 % ,可以分别避免 2 6 .7%和 1 1 .3%的人群进行活检。　结论 :在集团普查中 ,fPSA/tPSA比值在tPSA为 4 .0～ 2 0 .0 μg/L时可以提高检测PCa的特异性 ,减少不必要的活检。     

The significance of the free-to-complexed prostate-specific antigen (PSA) ratio in prostate cancer detection in patients with a PSA level of 4.1-10.0 ng/mL

OBJECTIVE: To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with alpha1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of < 30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone. CONCLUSION: Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1-10.0 ng/mL.     

Prostate cancer detection in men with a 'normal' total prostate-specific antigen (PSA) level using percentage free PSA: a prospective screening study

OBJECTIVE: To assess the utility of percentage free/total prostate-specific antigen (f/tPSA) levels for detecting prostate cancer in a prospectively screened population of men with a 'normal' total PSA level. PATIENTS AND METHODS: Men aged 50-65 years were contacted via their general practitioner and invited for prostate cancer screening. All had their total and f/tPSA levels measured; those meeting the biopsy criteria (PSA 1.1-3.99 ng/mL and f/tPSA < or = 20%) were offered a biopsy. The cancer detection rate was then evaluated and compared with other methods of detection. In all, 773 men were screened, of whom 115 met the criteria and agreed to undergo a prostate biopsy. RESULTS: Cancer was detected in 13 of the 115 men (11.3%) of whom most would have been missed by lowering the age-adjusted threshold for total PSA to 2.5 ng/mL. There was no significant difference in total and f/tPSA values in men with and without prostate cancer. Those cancers that could be evaluated were found to be clinically significant. CONCLUSION: In this study prostate cancer was detected solely on the basis of a low f/tPSA value. Most men with cancer would have been missed by simply lowering the age-adjusted threshold for total PSA. Using the f/tPSA level may allow the detection of clinically significant cancer in men at a time when they are most likely to benefit from treatment.     

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.     

Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) for the detection of prostate cancer has poor specificity in men with PSA levels between 2 and 10 ng/ml. It has been suggested that measurement of the ratio of free to total PSA (f/tPSA) or complexed PSA (cPSA) might offer an improvement. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of these tests among men with PSA levels between 2 and 10 ng/ml. METHODS: Data on sensitivity and specificity were extracted from 66 eligible studies. Likelihood ratios and summary receiver operating characteristic curves were estimated and possible sources of heterogeneity between studies examined. RESULTS: Use of the f/tPSA or the cPSA test improved diagnostic performance among men with a total PSA (tPSA) of 2-4 or 4-10 ng/ml compared to tPSA alone. The diagnostic performance of the f/tPSA test was significantly higher in the tPSA range of 4-10 ng/ml compared to a tPSA range of 2-4 ng/ml (p < 0.01); at a sensitivity of 95%, the specificity was 18% in the 4-10 ng/ml tPSA range and 6% in the 2-4 ng/ml tPSA range. Among studies that measured both isoforms, the diagnostic performance of the f/tPSA test and the cPSA was equivalent in both PSA ranges. CONCLUSIONS: The use of the f/tPSA or cPSA test among men with PSA levels between 2 and 10 ng/ml can reduce the number of unnecessary biopsies whilst maintaining a high cancer detection rate.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Incidental acute prostatic inflammation is associated with a lower percentage of free prostate-specific antigen than other benign conditions of the prostate: a prospective screening study

OBJECTIVE: To evaluate the performance of percentage free/total prostate-specific antigen (f/tPSA) as a screening tool for prostate cancer, and to assess the impact of prostatic inflammation on f/tPSA. PATIENTS AND METHODS: Men aged 50-65 years were invited for prostate cancer screening. Biopsies were taken from men with a tPSA of > or = 4 ng/mL, together with those with a tPSA of 1.1-3.99 ng/mL and a f/tPSA of < or = 20%. Histological evidence of prostate cancer, acute inflammation, chronic inflammation, and benign prostatic tissue were noted in biopsy cores, together with the associated f/tPSA values. RESULTS: The cancer detection rate was 4.3% (33/773). Evidence of inflammation was found in about half (87/175) of those biopsied. Men with acute inflammation (27/175, 15%) had significantly lower serum f/tPSA values (mean 13.4%) than those with chronic inflammation (mean 16.6%, P = 0.002) and benign prostatic tissue (mean 15.7%, P = 0.034), but were similar to men with prostate cancer (mean 15.3%, P = 0.315). CONCLUSIONS: In this prospectively screened cohort of men, there was a high incidence of asymptomatic inflammation on prostatic histology; f/tPSA values were significantly lower in men with acute inflammation. This might explain the variability of f/tPSA in improving specificity when used as a screening tool for prostate cancer, and might also reduce its effectiveness in differentiating tumours with more aggressive potential.     

Contemporary use of complexed PSA and calculated percent free PSA for early detection of prostate cancer: impact of changing disease demographics

Objectives. To assess the diagnostic performance of complexed prostate-specific antigen (cPSA), total PSA (tPSA), and calculated free/total PSA (f/t PSA) ratios in the differentiation of benign disease from prostate cancer (CaP) using a contemporary patient cohort.Methods. The cPSA, tPSA, and calculated fPSA values were determined using the Bayer Immuno-1 system. To validate our calculated f/t PSA ratio, we also retrospectively measured fPSA using the Abbott AxSYM immunoassay system in archival pretreatment sera obtained between 1990 and 1997 from 362 men with clinically and biopsy-confirmed benign prostatic hyperplasia (n = 179) or CaP (n = 183). The diagnostic utility of tPSA, cPSA, and the calculated f/t PSA ratio was assessed using a contemporary test population consisting of sera prospectively collected between June 1999 and June 2000 from 3006 men who had recently undergone a systematic biopsy by urologists in clinical practices throughout the United States. This contemporary patient sample had biopsy diagnoses of either no evidence of malignancy (n = 1857) or CaP (n = 1149). All serum samples had tPSA values between 2.0 and 20.0 ng/mL.Results. The measured versus calculated f/t PSA ratios had a Pearson’s correlation coefficient of 0.9130 in the retrospectively studied population of 362 men. The areas under the receiver operating characteristic curves (ROC-AUCs) for the measured and calculated f/t PSA ratios were indistinguishable (69.6% versus 69.2%, respectively). In the contemporary population (n = 3006), the ROC-AUC for tPSA, cPSA, and the calculated f/t PSA ratio was 52.2%, 53.9%, and 58.4%, respectively. We also compared the diagnostic performance using published cutoffs for tPSA (greater than 4.0 ng/mL), cPSA (greater than 3.8 ng/mL), and the f/t PSA ratio (greater than 15% and greater than 25%) in tPSA reflex ranges of 2 to 20 ng/mL and 2 to 10 ng/mL. We found that both cPSA and the f/t PSA ratio (greater than 25% cutoff) outperformed tPSA and yielded similar results in terms of biopsies spared and cancers missed.Conclusions. The calculated f/t PSA ratio and cPSA perform equally well in terms of the improvement of specificity in the discrimination of benign disease and CaP. The f/t PSA ratio and cPSA provide clinical benefits over the use of tPSA alone, such as an increased sparing of unnecessary biopsies performed with a manageable degree of risk of delayed cancer detection.     

Early detection of prostate cancer in African-American men through use of multiple biomarkers: human kallikrein 2 (hK2), prostate-specific antigen (PSA), and free PSA (fPSA)

Recent studies have reported enhanced prostate cancer detection in Caucasians with serum human glandular kallikrein 2 (hK2) in combination with total- (tPSA) and free-prostate-specific antigen (fPSA). The purpose of this study is to validate these findings in an African-American patient cohort. A total of 137 African-American men were found by routine screening to have tPSA levels above 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn prior to biopsy of the prostate and Hybritech PSA, FPSA and hK2 (for research use only, not for use in diagnostic procedures) concentrations were determined on Beckman Coulter's Access immunoanalyzer. These independent variables and the ratios of percent fPSA (%fPSA), hK2/tPSA, hK2/fPSA, and hK2*tPSA/fPSA were compared between cancer and non-cancer groups. In all, 49 of 137 men had prostate cancer. hK2 and its calculated ratios outperformed tPSA on receiver operator characteristic (ROC) analysis, but %fPSA had statistically the highest area under the curve (AUC) at 0.801. When restricting the analysis to only the tPSA range of 4.0-10 ng/ml, hK2/fPSA yielded the highest AUC (0.721). The ratio of hK2/fPSA was also found to increase the positive predictive value (PPV) of the %fPSA ranges less than 10 and 10-25%. %fPSA offered the best performance and highest specificity in prostate cancer detection in African-American males over the entire range of tPSA. hK2/fPSA may offer modest improvement in the tPSA range of 4.0-10 ng/ml. Furthermore, hK2/fPSA can enhance the PPV of low %fPSA values. Therefore, the use of multiple biomarkers may ultimately increase the specificity of prostate cancer screening in African-American men.     

Computer simulated additional deep apical biopsy enhances cancer detection in palpably benign prostate gland

OBJECTIVES: The objective of this study was to use computer simulation to investigate the optimal biopsy scheme for enhancing the detection of cancer in palpably benign prostate glands. METHODS: The predominant distribution of palpably benign prostate cancer is anterior apex to mid-prostate. We used computer simulation to optimize apical samplings and to simulate the biopsy procedure, including angle and length. A total of 254 consecutive patients with palpably benign prostate glands underwent sextant biopsy plus two additional deep apical biopsies. RESULTS: Based on the computer simulation, lateral sextant and two additional medially located deep apical cores with a sagittal penetration angle of 80 degrees had the maximum cancer detection. Of the 254 patients, 58 (22.8%) had prostate cancer: 28 (48.3%) were positive only at the standard sextant sites, 12 (20.7%) were positive exclusively at the deep apical sites, and the remaining 18 (31.0%) were positive at both sites. Patients with gray-zone prostate-specific antigen (PSA) ranges of 4.1-10.0 ng/mL had increased cancer detection rates of 24% compared to sextant biopsy. Enhanced cancer detection by the deep apical biopsy was also evident in patients with a prostatic volume >40 cm3 (by 36.4%) and PSA 2.1-4.0 ng/mL (by 13.3%). CONCLUSIONS: Using a computer simulation-based biopsy scheme with deep apical sampling cores enhanced the detection of prostate cancer in palpably benign glands, especially in men with PSA ranges of 4.1-10.0 ng/mL or a gland volume of >40 cm3. Our approach with fewer sampling cores may have been more cost-effective than other extensive biopsy schemes, but further studies with larger samples are warranted.     

Distribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer

OBJECTIVE: To explore the distribution of total prostate specific antigen (PSA) and percentage free/total PSA (%f/tPSA) in healthy volunteers with no clinical evidence of prostate cancer, who participated in prostate cancer screening. SUBJECTS AND METHODS: PSA and %f/tPSA values from 2323 men, who participated in one of three annual prostate cancer screening events between 2004 and 2006, were tabulated according to age strata of 40-49, 50-59, 60-69 and 70-79 years. Local regression smoothing plots provided a graphical display of the relation between age and PSA or %f/tPSA, respectively. All PSA and %f/tPSA analyses were repeated for each age category after excluding, respectively, the top and the bottom 10% of PSA and %f/tPSA values. RESULTS: Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 25%. According to the age categories the PSA level and %f/tPSA medians within the entire cohort were, respectively, 0.7, 0.9, 1.3, 1.8 ng/mL and 28.0, 26.0, 24.0 and 25.0%. Of the 2323 men, 438 (18.9%) had a PSA level of >2.5 ng/mL and 1172 (50.5%) had a %f/tPSA of < or = 25%. When either a PSA level of >2.5 ng/mL or a %f/tPSA of < or = 25% were considered, 1235 (53.2%) had one or two abnormal values. Finally, if either a PSA level of >2.5 ng/mL or %f/tPSA of < or = 15% was used, 617 (26.6%) were considered abnormal. CONCLUSION: Half of men with no clinical evidence of prostate cancer should have PSA levels of <1.0 ng/mL and a %f/tPSA of >25%. A PSA level threshold of 2.5 ng/mL would require a biopsy in 20% of men and a %f/tPSA threshold of < or = 25% in half of the men. Alternatively, a %f/tPSA threshold of < or = 15% would decrease the probability to 15%.     

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer

OBJECTIVE: To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. SUBJECTS AND METHODS: We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. RESULTS: Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. CONCLUSION: The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.     

Clinical utility of human glandular kallikrein 2 within a neural network for prostate cancer detection

OBJECTIVE

To assess, using artificial neural networks (ANNs), human glandular kallikrein 2 (hK2), prostate‐specific antigen (PSA), and percentage free/total PSA (f/tPSA), for discriminating between prostate cancer and benign prostatic hyperplasia (BPH).

MATERIAL AND METHODS

Serum samples from 475 patients with prostate cancer (n = 347) or BPH (n = 128) within the PSA range of 1–20 ng/mL were analysed for tPSA, fPSA and hK2 (research assay, Toronto, Canada). Data were analysed in the ranges of 1–4, 2–4, 4–10, and 2–20 ng/mL tPSA. Back‐propagation ANN models with the variables PSA, f/tPSA, and hK2, hK2/fPSA and hK2/(f/tPSA) were constructed. The diagnostic validity was evaluated by receiver‐operating characteristic (ROC) curve analysis.

RESULTS

Whereas the median concentration of hK2 was not significantly different between patients with BPH or prostate cancer in any of the tPSA ranges, the f/tPSA, hK2/fPSA and hK2/(f/tPSA), and the hK2‐based ANN outputs were always significantly different between patients with prostate cancer or BPH. Using ROC curve comparison, all variables were significantly better than hK2 in all ranges. The hK2‐based ANN performed better than f/tPSA except in the 4–10 ng/mL tPSA range. At 90% and 95% sensitivity, the hK2‐based ANN was also significantly better than f/tPSA in the 1–4 ng/mL tPSA range. hK2/(f/tPSA) achieved equal results to the hK2‐based ANN except in the range 2–20 ng/mL tPSA.

CONCLUSIONS

The hK2‐based ANN improves the outcome of f/tPSA but not hK2/(f/tPSA) in almost all analysed subgroups. When comparing the results at 90% and 95% sensitivity the hK2‐based ANN only performed significantly better than f/tPSA in the lowest tPSA range. Only in lower tPSA ranges do hK2‐based ANNs show an advantage for further improving prostate cancer detection.

     

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）     

Comparison of two investigative assays for the complexed prostate-specific antigen in total prostate-specific antigen between 4.1 and 10.0 ng/mL

OBJECTIVES: To determine the ability of complexed prostate-specific antigen (cPSA) levels to diagnose prostate cancer. METHODS: Between September 1998 and March 1999, cPSA levels in 182 consecutive patients with an abnormal digital rectal examination (DRE) or a total PSA (tPSA; Tandem-R assay) level greater than 4.1 ng/mL were examined. Levels of cPSA were measured by the Markit-M PSA-ACT (alpha(1)-antichymotrypsin) assay (cPSA-MM) and Bayer Immuno 1 complexed PSA assay (cPSA-BI). Free PSA (fPSA) was measured by the Tandem-R free PSA assay. RESULTS: Of the 140 patients with tPSA between 4.1 and 10.0 ng/mL, 116 were histologically confirmed as having benign tissue; the remaining 24 were diagnosed with prostate cancer. To ensure a 92% sensitivity of cancer detection, a cutoff value for the tPSA, cPSA-MM, and cPSA-BI assays of 4.8 ng/mL, 2.7 ng/mL, and 4.6 ng/mL, respectively, was determined. The percentage of negative biopsies prevented at these cutoff (ie, specificity) values was 14%, 23%, and 24%. No significant differences among these three assays were found. At 92% sensitivity, the cutoff value for the fPSA/tPSA, fPSA/cPSA-MM, and fPSA/cPSA-BI ratios was 18%, 27%, and 18%, respectively. The specificity was 35%, 49%, and 51%. No significant differences were found among these three fPSA ratios. Significant differences were noted between tPSA and the fPSA/cPSA-MM ratio and between tPSA and the fPSA/cPSA-BI ratio. No differences were seen among the other PSA parameters. CONCLUSIONS: No difference in the ability of cPSA levels to distinguish prostate cancer and noncancer was observed between cPSA-MM and cPSA-BI or between their fPSA ratios. Only the fPSA/cPSA-MM and fPSA/cPSA-BI ratios provided significantly enhanced diagnostic performance compared with tPSA.     

PSAD在PSA 4～10ng患者前列腺癌诊断中的价值

目的探讨前列腺特异性抗原密度（PSAD）在前列腺特异性抗原（PSA）值介于4～10ng之间患者前列腺腺癌诊断中的应用价值。方法回顾性分析183例血清PSA值介于4～10ng之间疑似前列腺癌患者的临床资料,所有患者均经直肠B超测得前列腺体积后再行经直肠超声引导下前列腺穿刺术,通过接受者工作特征曲线分析法评价PSAD在预测诊断前列腺癌中的应用价值。结果 183例患者中36例经直肠超声下前列腺活检的患者被诊断为前列腺癌,占19.7%。良性前列腺增生组与前列腺癌患者之间,PSA（0.681 5）与PSAD（0.721 4）的曲线下方面积比较相似,而游离前列腺特异性抗原与总前列腺特异性抗原比值（f/tPSA）的曲线下面积只有0.318 2,相比PSA,PSAD值将是一个更好的预测前列腺癌的指标。结论 PSAD对于PSA值介于4～10ng/mL的中国患者是一项更好的预测前列腺癌的指标。