Preoperative prostate-specific antigen isoform p2PSA≤22.5 pg/ml predicts advanced prostate cancer in patients undergoing radical prostatectomy

BackgroundThe prediction value of prostate-specific antigen (PSA) isoform [?2]proPSA (p2PSA) for detecting advanced prostate cancer (PCa) remains unclear. Our objective was to evaluate the additional clinical utility of p2PSA compared with total PSA (tPSA), free PSA (fPSA), and preoperative Gleason score (Gls) in predicting locally advanced PCa (pT3/T4) with high-accuracy discrimination. The aim was to develop a novel classification based on p2PSA and preoperative Gls for predicting advanced PCa.Materials and methodsIn 208 consecutive men diagnosed with clinically localized PCa who underwent radical prostatectomy, we determined the predictive and discriminatory accuracy of serum tPSA, fPSA, percentage of fPSA to tPSA, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and the Prostate Health Index. The cutoff level of p2PSA with best accuracy was estimated. The novel classification was developed by analyzing the interaction between p2PSA and Gls in predicting pathologic outcomes using a chi-square automatic interaction detection analysis. Decision curve analysis was applied to test the clinical consequences of using the novel classification.ResultsOn univariate analyses, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and Prostate Health Index were accurate but were not independent predictors by multivariate analysis. The p2PSA cutoff level of 22.5 pg/ml showed the best accuracy level for predicting and discriminating advanced diseases (area under the curve [AUC] = 0.725, sensitivity = 51.4%, specificity = 81.8%). By chi-square automatic interaction detection, univariate and multivariate analysis, a p2PSA level>22.5 pg/ml was significantly associated with an increased frequency and risk of advanced disease. In patients with a p2PSA level≤22.5 pg/ml, 91.8% of Gleason sum 6 PCa was organ confined. The combination of p2PSA and Gls enhanced slightly but significantly the predictive and discriminatory accuracy for advanced disease (0.6%–3.6%).ConclusionsThe p2PSA cutoff level of 22.5 pg/ml can accurately discriminate between organ-confined and advanced PCa. The additional use of p2PSA enhanced slightly the predictive accuracy for advanced PCa (pT3/pT4) and has limited additional predictive value in identifying aggressive PCa (Gls>7a).     

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.     

Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer

Background

Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New biomarkers would be welcome.

Objective

Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP.

Design, setting, and participants

An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP.

Measurements

We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml.

Intervention

Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeon's judgement.

Results and limitations

The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading (all p values <0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume <0.5 ml (p < 0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum.

Conclusions

We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.     

PSA密度在PSA 2.5～10.0 ng/mL和10.1～20.0 ng/mL患者前列腺癌诊断价值的多中心研究

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)值位于2.5~10 ng/m L和10.1~20.0 ng/m L患者前列腺癌诊断的效能。方法回顾性分析广州地区两家医院中PSA在2.5~20.0 ng/m L之间,行经直肠前列腺体积测量并行前列腺穿刺的461名患者临床资料,入选者分为PSA 2.5~10.0 ng/m L和PSA10.1~20.0 ng/m L两组,通过受试者工作特征曲线(ROC)分析法评价PSAD与PSA在预测前列腺癌的诊断效力。结果 PSA 2.5~10.0 ng/m L和PSA 10.1~20.0 ng/ml两组的曲线下面积比较,PSAD均高于PSA。在PSA 2.5~10.0 ng/m L组,PSAD预测前列腺癌的最佳临界点为0.15 ng·m L~(-1)·m L~(-1),敏感性和特异性分别为64.4%和64.6%;在PSA10.1~20.0 ng/m L组,PSAD预测前列腺癌的最佳临界点为0.33 ng·m L~(-1)·m L~(-1),敏感性和特异性分别为60.3%和82.7%。结论对于PSA2.5~10.0 ng/m L和10.1~20.0 ng/m L的中国男性,PSAD是一种更优的前列腺癌预测指标。     

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.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.     

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.     

建立前列腺特异性抗原灰区患者重复穿刺阳性的数学模型

目的:建立预测前列腺特异性抗原(PSA)灰区患者重复穿刺阳性的数学模型。方法:选择2004~2016年158例血清PSA位于4~10ng/ml且首次穿刺病理结果为阴性的患者行重复穿刺,记录并分析患者的年龄、前列腺体积(PV)、PSA、游离PSA(fPSA)/总PSA(tPSA)、前列腺特异性抗原速率(PSAV)、前列腺特异抗原密度(PSAD)、前列腺移行带特异性抗原密度(PSAD-TZ)、超声检查(TRUS)、直肠指检(DRE)、高级别上皮内瘤变(HGPIN)、不典型小腺泡增生(ASAP)等重复活检结果的潜在预测指标。将有统计学意义的变量行二分类Logistic回归分析和建立数学模型,该模型的预测价值通过ROC曲线下面积(AUC)来评估。结果:158例前列腺重复穿刺活检患者中,前列腺癌的检出率为25.9%(41/158),单变量分析结果中统计学上有意义的指标包括Age、PV、f/tPSA、PSAD、PSAD-TZ、DRE、TRUS、Previous HGPIN、Previous ASAP(P<0.05),对以上所有变量进行二分类Logistic回归分析并建立数学模型,预测指标ASAP、HGPIN、f/tPSA、TRUS、DRE被纳入该模型。该模型AUC为89.8%,预测价值较高。结论:该数学模型可以很好的预测PSA患者重复穿刺阳性的概率,能够帮助临床医师判断哪些PSA灰区患者更适合行超声引导下前列腺重复穿刺活检术。     

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）     

Prostate cancer detection in the "grey area" of prostate-specific antigen below 10 ng/ml: head-to-head comparison of the updated PCPT calculator and Chun's nomogram, two risk estimators incorporating prostate cancer antigen 3

Background

Prostate cancer antigen 3 (PCA3) holds promise in diagnosing prostate cancer (PCa), but no consensus has been reached on its clinical use. Multivariable predictive models have shown increased accuracy over individual risk factors.

Objective

To compare the performance of the two available risk estimators incorporating PCA3 in the detection of PCa in the “grey area” of prostate-specific antigen (PSA) <10 ng/ml: the updated Prostate Cancer Prevention Trial (PCPT) calculator and Chun's nomogram.

Design, setting, and participants

Two hundred eighteen patients presenting with an abnormal PSA (excluding those with PSA >10 ng/ml) and/or abnormal digital rectal examination were prospectively enrolled in a multicentre Italian study between October 2008 and October 2009. All patients underwent ≥12-core prostate biopsy.

Measurements

PCA3 scores were assessed using the Progensa assay (Gen-Probe, San Diego, CA, USA). Comparisons between the two models were performed using tests of accuracy (area under the receiver operating characteristic curve [AUC-ROC]), calibration plots, and decision curve analysis. Biopsy predictors were identified by univariable and multivariable logistic regression. In addition, performance of PCA3 was analysed through AUC-ROC and predictive values.

Results and limitations

PCa was detected in 73 patients (33.5%). Among predictors included in the models, only PCA3, PSA, and prostate volume retained significant predictive value. AUC-ROC was higher for the updated PCPT calculator compared to Chun's nomogram (79.6% vs 71.5%; p = 0.043); however, Chun's nomogram displayed better overall calibration and a higher net benefit on decision curve analysis. Using a probability threshold of 25%, no high-grade cancers would be missed; the PCPT calculator would save 11% of biopsies, missing no cancer, whereas Chun's nomogram would save 22% of avoidable biopsies, although missing 4.1% non–high-grade cancers. The small number of patients may account for the lack of statistical significance in the predictive value of individual variables or model comparison.

Conclusions

Both Chun's nomogram and the PCPT calculator, by incorporating PCA3, can assist in the decision to biopsy by assignment of an individual risk of PCa, specifically in the PSA levels <10 ng/ml.     

The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy

PURPOSE: It has recently been suggested that the diagnostic threshold for the prostate specific antigen (PSA) assay be lowered to enhance prostate cancer detection. A 22% incidence of prostate cancer has been reported in men with PSA between 2.5 and 4.0 ng/ml. We designed a study to confirm this observation. MATERIALS AND METHODS: Men who participated in our free early detection program and who had serum PSA between 2.5 and 4.0 ng/ml were asked to undergo prostate biopsy. Of 268 eligible men 151 (56%) agreed to participate in this free trial. All men underwent biopsy using an 11-core multisite directed biopsy scheme. All biopsy cores were color coded for location specificity and examined by 1 pathologist. RESULTS: Cancer was identified in 24.5% (37 of 151) of the men biopsied. The median age of men with cancer was 62 years (range 43 to 74). Conventional systematic sextant biopsies, which accounted for 6 of the 11 cores, detected 73.0% (27 of 37) of the cancers and the alternate site biopsies identified the remaining 10. Gleason score was 6 in 25 men, 3 + 4 in 5, 4 + 3 in 4 and 8 or greater in 3 (median Gleason score 6). There were 14 men who had 1 core positive for cancer, 9 had 2 and 14 had more than 2 (median number of positive cores 2). Of the 14 men with 1 positive core 11 had a less than 3 mm focus of cancer and 8 had only a positive alternate site biopsy. There were 11 cases of abnormal results on digital rectal examination, 5 of which were cancer, and 31 cases of abnormal results on ultrasonography, 13 of which were cancer. Median biological variability in PSA was +/-15% (range 0.4% to 440.0%). CONCLUSIONS: We found a significant incidence of cancer (24.5%, 37 of 51) in men with serum PSA between 2.5 and 4.0 ng/ml. In our study 67.6% of the detected cancers were significant based on the biopsy data. If the PSA threshold is lowered the conventional systematic sextant technique may be preferable to an extended strategy.     

Development, validation, and head-to-head comparison of logistic regression-based nomograms and artificial neural network models predicting prostate cancer on initial extended biopsy

OBJECTIVES: Using cohorts examined by extended biopsy, we developed and validated multivariate models predicting prostate cancer on initial biopsy and examined whether these extended biopsy-based models outperform previously established models. METHODS: Initial extended biopsy (median 22 cores) was performed in 1509 Japanese men including 1083 at Tokyo Medical and Dental University Hospital (TMDU) and 426 at Cancer Institute Hospital (CIH). Logistic regression-based nomograms 1 and artificial neural network (ANN) 1 incorporating age, digital rectal examination, and prostate-specific antigen (PSA) and free PSA, and nomogram 2 and ANN2 further incorporating transrectal ultrasound (TRUS) findings and prostate volume were constructed on the TMDU data. These and previously established models were externally validated on the CIH data set and predictive accuracy was compared directly. RESULTS: Without TRUS-derived information, nomogram 1 outperformed the ANN1. With TRUS-derived information, nomogram 2 was more accurate than ANN2. External validation revealed applicability of the Western models to Japanese population, superiority of the nomograms over ANN models, and better predictive accuracy of our extended biopsy-based nomograms than the previous 6-10-core biopsy-based models. Using nomograms 1 and 2, 16% and 19% unnecessary biopsies would be saved at 95% sensitivity. CONCLUSIONS: We developed new nomograms predicting prostate cancer on initial biopsy in men with PSA <20ng/ml. Predictive accuracy of these extended biopsy-based nomograms is better than those of previously established models based on 6-10-core biopsies. Our models might help clinicians to decide if a patient requires biopsy and to avoid unnecessary biopsies.     

Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range

PURPOSE: Percent free prostate specific antigen (PSA) is useful to select patients for prostate biopsy with total PSA 4 to 10 ng./ml. However, 20% of men with PSA between 2.6 and 4 ng./ml. harbor significant prostate cancer and percent free PSA has been suggested to aid in the decision to biopsy in this total PSA range as well. Concerns exist that the number of biopsies needed to detect 1 cancer in this range may be inappropriately high. In a prospective referral population we evaluated sensitivity and specificity of various percent free PSA cutoffs and determined the biopsy-per-cancer ratio in the PSA 2 to 4 ng./ml. range in men with a benign digital rectal examination, and report on the biological nature of the detected cancers based on Gleason score. Results were compared to those obtained from a reference group of patients (PSA 4 to 10 ng./ml., benign digital rectal examination) from the same prospective referral cohort. MATERIALS AND METHODS: Total PSA and free PSA were measured and percent free PSA was calculated. Of the initial 1,602 men 756 had a benign digital rectal examination and PSA 4 to 10 ng./ml., and 219 had a benign digital rectal examination and PSA 2 to 4 ng./ml. Sensitivity, specificity, the number of true positive (evidence of cancer) and false-positive (no evidence of cancer) biopsies were determined. The ratio of true positive biopsies-to-all biopsies performed was used to determine the biopsy-per-cancer ratio. Gleason score of the detected cancers was evaluated. The procedure was repeated for the PSA 4 to 10 ng./ml. range. RESULTS: In the PSA 4 to 10 ng./ml. range a sensitivity of 63.7% to 92.5% with a specificity of 57.5% to 18.7% was found when percent free PSA was 18% to 25%. On average 3 biopsies were needed to detect 1 cancer. When PSA was 2 to 4 ng./ml. sensitivity was 46.3% to 75.6% and specificity was 73.6% to 37.6% when the same percent free PSA cutoff was examined. Calculation of the biopsy-per-cancer ratio for various percent free PSA cutoffs revealed that 3 to 5 biopsies were needed to find 1 cancer. Of 41 cancers detected in the PSA 2 to 4 ng./ml. range 6 had a Gleason score 5. The majority (28 of 41) of cases had a Gleason score of 6. Gleason score was 7 in 5 patients and 8 in 1. CONCLUSIONS: In the PSA 4 to 10 ng./ml. range high sensitivity for prostate cancer detection is critical and 3 biopsies are needed to detect 1 cancer. In the PSA 2 to 4 ng./ml. range a percent free PSA cutoff of 18% to 20% detected about 50% of cancers while sparing up to 73% of unnecessary biopsies with a biopsy-to-cancer ratio of 3 to 4:1. Percent free PSA can be applied to the PSA 2 to 4 ng./ml. range to detect prostate cancer and only moderately increases the number of biopsies needed to detect 1 significant cancer compared to the greater than 4 to 10 ng./ml. range.     

Predictors of prostate cancer on repeat prostatic biopsy in men with serum total prostate-specific antigen between 4.1 and 10 ng/mL

OBJECTIVES: We determine whether the different molecular forms of prostate-specific antigen (PSA) and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy. METHODS: Between 1997 and 2001, repeat biopsy was performed in 97 patients who had undergone prior negative prostate biopsy. The ability of total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), free-to-total PSA (fPSA/tPSA), free-to-complexed PSA (fPSA/cPSA), complexed-to-total PSA (cPSA/tPSA), tPSA density (tPSAD), cPSA density (cPSAD), transition zone tPSA density (tPSATZ) and transition zone cPSA density (cPSATZ) was assessed by univariate and multivariate analyzes as well as receiver operating characteristics (ROC) curves. RESULTS: Prostate cancer on repeat biopsy was detected in 24% of subjects (23 of 97) who had a negative initial biopsy. The PSA parameters cut-off to ensure a 96% sensitivity of cancer detection, were 29% using fPSA/tPSA, 32% using fPSA/cPSA, 0.18 ng/mL/cc using tPSATZ and 0.16 ng/mL/cc using cPSATZ. The fPSA/tPSA would have prevented 32% of negative biopsies, the fPSA/cPSA 28%, the tPSATZ 23% and the cPSATZ 30%. ROC curve analysis fPSA/tPSA, fPSA/cPSA ratios, tPSATZ and cPSATZ were significantly better predictors of repeat biopsy results than tPSA or cPSA, but there was no significant difference in the ROC curves among these four PSA parameters. In the multivariate logistic regression analysis these four PSA parameters were significant predictors for cancer detection in the repeat biopsy group (P < 0.001). CONCLUSION: fPSA/tPSA ratio, fPSA/cPSA ratio, tPSATZ and cPSATZ enhance the specificity of PSA testing compared to tPSA or cPSA when determining which patients should undergo repeat biopsy.     

Complexed prostate specific antigen density is better than the other PSA derivatives for detection of prostate cancer in men with total PSA between 2.5 and 20 ng/ml: results of a prospective multicenter study

PURPOSE: This prospective, multicenter study was initiated to evaluate the diagnostic performance of PSA, free/total PSA (f/tPSA) and complexed PSA (cPSA) with volume-based parameters for early detection of prostate cancer in patients with PSA between 2.5 and 20 ng/ml. MATERIALS AND METHODS: 408 subjects with serum PSA values between 2.5 and 20 ng/ml regardless of digital rectal examination (DRE) were included in to the study. The diagnostic validity, sensitivity, specificity and cut-off values were evaluated by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Of 408 patients 77 (18.9%) were positive for prostate cancer. Digital rectal examination was non-suspicious in 86% (351/408) of the patients. Area under curve (AUC) values for cPSA were better than PSA and f/tPSA in patients with PSA values of 2.5-10 ng/ml and 4-10 ng/ml, as well as the whole group. Furthermore, on ROC curve analysis cPSAD was the best predictor of prostate cancer for all PSA ranges regardless of the DRE findings except PSA values between 2.5 and 4 ng/ml. The cut-off value of cPSAD at 90% sensitivity was 0.06 ng/ml/cm(3) with a 35.3% specificity saving 126 unnecessary biopsies in the whole group. CONCLUSION: cPSA might be a better initial test than PSA for prostate cancer detection and measurement of cPSA alone and its derivatives obviate the need for additional fPSA testing.     

PSA density improves the rate of prostate cancer detection in Chinese men with a PSA between 2.5–10.0 ng ml-1 and 10.1–20.0 ng ml-1: a multicenter study

Chinese men should have a higher prostate-specific antigen (PSA) “gray zone” than the traditional value of 2.5–10.0 ng ml⁻¹ since the incidence of prostate cancer (PCa) in Chinese men is relative low. We hypothesized that PSA density (PSAD) could improve the rate of PCa detection in Chinese men with a PSA higher than the traditional PSA “gray zone.” A total of 461 men with a PSA between 2.5 and 20.0 ng ml⁻¹, who had undergone prostatic biopsy at two Chinese centers were included in the analysis. The men were then further divided into groups with a PSA between 2.5–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of PSA and PSAD for the diagnosis of PCa. In men with a PSA of 2.5–10.0 ng ml⁻¹ or 10.1–20.0 ng ml⁻¹, the areas under the ROC curve were higher for PSAD than for PSA. This was consistent across both centers and the cohort overall. When the entire cohort was considered, the optimal PSAD cut-off for predicting PCa in men with a PSA of 2.5–10.0 ng ml⁻¹ was 0.15 ng ml⁻¹ ml⁻¹, with a sensitivity of 64.4% and specificity of 64.6%. The optimal cut-off for PSAD in men with a PSA of 10.1–20.0 ng ml⁻¹ was 0.33 ng ml⁻¹ ml⁻¹, with a sensitivity of 60.3% and specificity of 82.7%. PSAD can improve the effectiveness for PCa detection in Chinese men with a PSA of 2.5–10.0 ng ml⁻¹ (traditional Western PSA “gray zone”) and 10.1–20.0 ng ml⁻¹ (Chinese PSA “gray zone”).