Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection

PURPOSE: To examine value of prostate-speci fi c antigen (PSA) adjusted by prostate volume measured using transabdominal ultrasonography in prostate cancer detection among men with elevated PSA. METHODS: 238 men aged 79 years or younger with serum PSA levels of 2.0-20.0 ng/mL and normal digital rectal examination fi ndings were studied in terms of total and free PSA, prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography and transition zone volumes with TRUS prior to transrectal 10-core biopsy. In addition to sole PSA values and the free-to-total PSA ratio, volume-adjusted PSA values, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic (ROC) analysis. RESULTS: Prostate cancer was diagnosed in 58 (24.4%) of the 238 men who underwent prostate biopsies. Of the areas under ROC curves (AUC) of studied parameters, PSATzD (AUC 0.751) was the best and signi fi cantly superior to PSAD(TAUS) (AUC 0.664, P = 0.007). However, PSAD(TAUS) exceeded PSA (AUC 0.559, P = 0.004) and showed potential capability of a one-fourth reduction in unnecessary biopsies without spoiling sensitivity (90%). Cancer detection rate was only 4.2% in the 48 patients whose prostate volume in TAUS was > 50 mL and PSAD(TAUS) was < 0.075. CONCLUSIONS: Since PSAD(TRUS) and PSATzD were signi fi cantly superior to PSAD(TAUS), TRUS is feasible as the standard fashion to determine prostate volume in the diagnosis of prostate cancers. However, TAUS is also worthwhile as it can improve the prostate cancer detection using sole PSA, and primary use of TAUS has the potential to reduce the substantial number of unnecessary biopsy safely.     

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.     

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

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

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。     

Early detection of prostate cancer in the ESRD population

BACKGROUND: There are currently no prostate cancer screening guidelines specific to the end-stage renal disease (ESRD) population. With this in mind, we evaluated the clinical usefulness of digital rectal examination (DRE), serum total prostate-specific antigen (PSA), prostate-specific antigen density (PSAD) and transrectal ultrasound (TRUS) in predicting prostate cancer in men with ESRD. METHODS: Fifty male ESRD patients age 40 years and older with no prior history of prostate cancer were enrolled in the study. All patients underwent PSA measurement and a DRE followed by a TRUS. PSAD was calculated as the total PSA divided by the prostate volume. Ultrasound-guided prostate biopsies were performed on any patient with 1 or more of the following abnormal findings: a nodule detected on DRE; an abnormal TRUS; PSA > 4.0 ng/ml, or a PSAD > 0.15 ng/ml/cm3. RESULTS: Abnormal findings were detected in 19 patients. Two (4%) had an abnormal DRE, 3 (6%) had PSA > 4.0 ng/ml, 3 (6%) had PSAD > 0.15 ng/ml/cm3 and 16 (32%) had abnormal findings on TRUS. Three patients had 2 abnormal findings and 1 had 3. Of the 15 prostate biopsies performed, 4 (27%) revealed prostate cancer and 3 (20%) high-grade prostatic intraepithelial neoplasm (HGPIN) comprising 8% and 6%, respectively, of the studied population. Of the 4 patients diagnosed with prostate cancer, none had abnormal DRE, 2 (50%) had PSA > 4.0 ng/ml (sensitivity = 66.7% and PPV = 50% (p = 0.236)), 3 (75%) had PSAD > 0.15 ng/ml/cm3 (sensitivity = 100% and PPV = 75% (p < 0.018)), and 3 (75%) had abnormal findings on TRUS (sensitivity = 30% and PPV = 75% (p = 1.000)). CONCLUSION: Routine screening with PSA and DRE does not seem sensitive enough to predict the presence of the disease. Although TRUS detected abnormalities in 16 patients (32%), sensitivity was very low (30%). In our patients, PSAD increased the sensitivity and positive predictive value (PPV) of detecting prostate cancers compared to PSA alone.     

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.     

Examination for indication of systematic biopsy for diagnosis of prostate cancer]

BACKGROUND: Systematic biopsy has been commonly used for detection of prostate cancer. Nevertheless, as this examination occasionally gives patients severe complications it is necessary to give careful consideration for application of this examination. Thus, we analyzed retrospectively 145 cases who underwent transrectal ultrasonography (TRUS) guided systematic biopsy to evaluate the application of systematic biopsy, correlating with the findings of digital rectal examination (DRE), prostate specific antigen (PSA), the findings of transrectal ultrasonography (TRUS) and the results of biopsies. METHODS: Between May, 1995 and May, 1997, 143 patients who were suspected to have prostate cancer with either of PSA and DRE, and 2 patients who received visual laser ablation of prostate (VLAP), underwent TRUS guided systematic biopsy of prostate. We evaluated diagnostic efficacy of PSA, DRE, TRUS, prostate-volume-specific PSA, and PSA density (PSAD). RESULTS: Sensitivity, specificity and positive predictive value (P.P.V.) are 78.4%, 62.8% and 53.5% for DRE, 100.0%, 4.4% and 41.8% for PSA, 88.2%, 60.0% and 52.9% for TRUS, 87.8%, 72.1% and 64.2% for prostate-volume-specific PSA, 100.0%, 30.6% and 45.4% for PSAD, respectively. Ten of 69 patients (14.5%) whose PSA levels were 4.0 to 10.0 ng/ml were diagnosed as cancer, and positive for both or either of DRE and TRUS. Twenty-seven who were negative for both of DRE and TRUS were not diagnosed as prostate cancer. Using the combination of prostate-volume-specific PSA, DRE and TRUS, we could eliminate 29 non-cancer men (21.5%) whose PSA level was greater than 4.0 ng/ml from systematic biopsy. CONCLUSION: On the diagnosis of prostate cancer, the combination of prostate-volume-specific PSA, DRE and TRUS is very useful to exclude unnecessary systematic biopsy, if an urologist could be used to and trained for DRE and TRUS.     

以前列腺特异抗原水平分组筛查与前列腺穿刺阳性率的关系

目的探讨不同血清前列腺特异抗原(PSA)水平前列腺癌检出情况以及直肠指诊(DRE)、经直肠超声检查(TRUS)、PSA密度(PSAD)等指标对筛查前列腺穿刺活检病例的意义。方法回顾性分析在1996年4月至2002年12月间行TRUS引导前列腺6点系统穿刺活检的634例患者的诊断资料,对各PSA组(≤4.0,4.1~,10.1~和>20.0μg/L组)中前列腺癌的检出率,以及PSA、DRE、TRUS、PSAD等对前列腺癌的预测作用进行t检验、χ2检验和多因素Logistic回归分析。结果PSA≤4.0,4.1~,10.1~和>20.0μg/L各组的前列腺癌检出率分别为11.6%(17/146),26.8%(38/142),39.8%(68/171)和68.6%(120/175)。PSA的敏感性最高(93.0%),特异性低(33.0%);DRE、TRUS等诊断效率较低。随血清PSA水平升高,前列腺癌检出率以及DRE、TRUS的阳性预测值逐渐升高;在PSA4.1~20.0μg/L者中,PSAD对前列腺癌有较大的预测价值(OR=687.09±646.96,P=0.000)。以PSAD≥0.13μg.L-1.cm-3为截点筛查前列腺穿刺病例,可在不明显降低敏感性的基础上,减少阴性穿刺。结论各PSA组国人与欧美等国前列腺癌检出率有较大差别;DRE、TRUS的筛查作用与血清PSA水平有关;按PSA水平分组筛查穿刺病例,可提高前列腺穿刺的阳性率。     

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the G?teborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.     

The value of prostatic specific antigen density in the early diagnosis of prostate cancer

In order to differentiate benign from malignant prostatic lesions, 42 patients were evaluated using the prostate specific antigen density (PSAD) test. All patients were evaluated with PSA determination, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and ultrasound-guided prostatic biopsies. PSA was analyzed by the I-MX ABBOT assay. PSAD was determined by dividing the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer in 3 of the 42 patients (6.38%). It is concluded that PSAD is valuable for the early diagnosis of localized prostatic carcinoma, especially when there are negative findings from DRE and/or TRUS.     

Usefulness and predictive value of PSA density, adjusted by transition zone volume, in men with PSA levels between 2 and 4 ng/ml

ObjectiveTo assess the diagnostic significance of prostate-specific antigen (PSA), density (PSAD) accuracy, and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.0 and 4.0 ng/ml.Material and methodsBetween 2000 and 2010, 138 men with PSA levels between 2 and 4.0 ng/ml underwent transrectal ultrasonography (TRUS) and 12-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml.ResultsThe detection rate of prostate cancer was 23,8% (32/134). The percentage of patients with extracapsular disease was 28.1% (10/32) and primary Gleason grade 4 or 5 was obtained in 8/32 (25%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively.ConclusionsThe use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.0 to 4.0 ng/ml.     

Community‐based prostate cancer screening in Japan: Predicting factors for positive repeat biopsy

Objectives: To assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. Methods: A total of 50 207 men over 55 years‐of‐age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate‐specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. Results: A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat‐biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05–18.5), 4.15 (1.31–14.0), and 3.62 (1.06–13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. Conclusions: A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high‐risk patients with an initial negative biopsy.     

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.     

Measurement of PSA density by 3 imaging modalities and its correlation with the PSA density of radical prostatectomy specimen

ObjectiveTo evaluate the difference between the PSA density (PSAD) calculated with 3 imaging modalities and the PSAD of the radical prostatectomy specimen.Materials and methodsThe PSAD of 60 men with clinically localized prostate cancer was calculated with transabdominal ultrasound (TAUS), transrectal ultrasound (TRUS), and computed tomography (CT) before radical retropubic prostatectomy, and was compared with the PSAD of the surgical specimen using the paired t-test. The relationship of the real prostate volume and the difference between the PSAD calculated with the 3 imaging modalities and that of the PSAD of the specimen was analyzed using Pearson's correlation coefficient. Finally, the sensitivity of PSAD calculated with the examined imaging modalities and the specimen was also studied.ResultsThe mean difference between the PSAD calculated by each one of the 3 imaging modalities and the PSAD of the specimen was ?0.01 ng/ml/cm³ (P = 0.28) for TAUS, 0.01 ng/ml/cm³ (P = 0.37) for TRUS, and ?0.03 ng/ml/cm³ (P = 0.001) for CT. This difference has not been shown to depend on the real prostate volume according to Pearson's correlation coefficient, which was 0.056 (P = 0.673) for TAUS, ?0.014 (P = 0.917) for TRUS, and 0.184 (P = 0.159) for CT. The sensitivity of PSAD calculated with TAUS, TRUS, and CT was 58.3%, 65%, and 45%, respectively, while that of the specimen was 70%.ConclusionsAlthough PSAD showed a moderate sensitivity, TRUS and TAUS are the imaging modalities that calculate it closer to the real PSAD of the specimen.     

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.     

Evaluation of Prostate Specific Antigen Density and Transrectal Ultrasonography-Guided Biopsies in 100 Consecutive Patients with a Negative Digital Rectal Examination and Intermediate Serum Prostate Specific Antigen Levels

Background : This study was undertaken to assess the importance of prostate biopsies in patients with a negative digital rectal examination (DRE) and elevated prostate specific antigen (PSA) levels and to investigate the role of PSA density (PSAD) and hypoechoic lesions on transrectal ultrasound (TRUS) in increasing the diagnostic sensitivity and specificity for prostate cancer (PCa). Methods : One hundred patients with varied initial symptoms who had a negative DRE and a PSA level between 4 and 20ng/mL underwent TRUS-guided systematic and, if present, lesion-directed biopsies. Results : PCa was detected in 11 patients (11%). TRUS examinations revealed hypoechoic lesions in 31 patients. Lesion-directed biopsies revealed PCa in 1 3% (4/31) of patients with abnormal TRUS whereas, 7% (5/69) of patients with negative TRUS findings had PCa. Additional systematic biopsies detected PCa in 2 patients where lesion-directed biopsies were negative. None (0/19) of the lesions smaller than 0.2 ml on TRUS had PCa whereas, 33% (4/1 2) of patients with lesions greater than 0.2 ml had PCa. When the subgroup of patients with negative TRUS and PSA levels between 4 and 10ng/mL were considered, 25% (1/4) of cases with PCa would have been missed if 0.15 was used as the cut-off point for PSAD, however, this would save 61% (30/49) of unnecessary biopsies. The positive predictive value of PSA (cut-off level lOng/mL), PSAD (cut-off level 0.15), and hypoechoic lesions on TRUS were found to be 11.5%, 33%, and 13%, respectively. When hypoechoic lesions greater than 0.2 mL were taken as the positive finding, the positive predictive value and specificity rates of TRUS increased to 33% and 91 %, respectively, without any change in the sensitivity. Conclusions : In patients with a negative DRE and intermediate PSA levels, the application of PSAD would have saved 49% of study patients with BPH from a biopsy, but would have missed 27% of PCa cases. By ignoring lesions smaller than 0.2 mL on TRUS, a very high specificity of 91% was achieved with a sensitivity of 36%. Thus, further investigations aimed at defining a better mode of diagnosis of PCa are warranted.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.     

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density

Summary Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1–10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important. The use of PSAD provides unique information regarding the need for biopsy and the likelihood of CaP. At PSA levels ranging between 10.1 and 20.0 ng/ml, PSAD will identify those patients who are less likely to have CaP, but all should undergo biopsy. If the PSA value is >20 ng/ml, all patients should undergo a biopsy.     

建立预测中国人前列腺重复穿刺活检阳性的数学模型

目的:建立可以预测国人经直肠超声引导下重复穿刺活检阳性的数学模型。方法:170例在首次穿刺活检诊断为前列腺良性病变的患者行重复穿刺。记录并分析患者的年龄、前列腺体积、血清PSA、游离PSA(f-PSA)/总PSA(t-PSA)、PSA上升速度、PSA密度(PSAD)、直肠指检(DRE)、首次穿刺病理结果等相关因素。将变量通过逐步回归建立回归方程,在此基础上建立重复穿刺活检阳性的危险评分数学模型。该模型的预测价值通过受试者工作曲线下面积来评估。结果:170例前列腺重复穿刺活检的患者中,前列腺癌的穿刺检出率为31.8%(54/170)。建立的数学模型影响因素包括:患者的年龄、前列腺体积、PSA、f-PSA/t-PSA、PSA上升速度、PSAD、DRE、首次穿刺结果是否为上皮内瘤变。该模型预测价值较高,曲线下面积为82.4%,大于患者PSAD、前列腺体积、PSA上升速度、f-PSA/t-PSA、DRE等单因素的66.9%、72.6%、69.6%、69.3%、58.5%。结论:该数学模型是临床多因素综合分析基础上建立的,可以很好地预测前列腺重复穿刺活检阳性的概率。     

Prospective Evaluation of Prostate Specific Antigen (PSA), PSA Density,Free-to-Total PSA Ratio and a New Formula (Prostate Malignancy Index) for Detecting Prostate Cancer and Preventing Negative Biopsies in Patients with Normal Rectal Examinations and Intermediate PSA Levels

Objective: To improve the specificity and sensitivity of prostatic cancer detection, we prospectively evaluated total prostate specific antigen (PSA) level, PSA density, free-to-total PSA ratio and a new formula called prostate malignancy index (PMI) as a discriminator of prostate cancer in patients with intermediate PSA levels and normal digital rectal examinations. Materials and methods: Between November 1995 and October 1997, 95 patients who had serum PSA levels of 4.0 to 10.0 ng/ml with normal digital rectal examinations were prospectively evaluated. All patients underwent one or two times transrectal ultrasound guided prostate biopsies. Based on age specific reference range of PSA, PSA density and % free PSA ratio, PMI was calculated for each patient. The free and total serum PSA concentrations were determined by an Immulite assay system. (Diagnostic Product Corp., Los Angeles, California). Results: Overall 20 of 95 (21%) patients had prostate cancer. There were no significant differences in patient mean age and mean total PSA between those with benign and those with malignant biopsies (p>0.05). However, there were significant differences in mean PSAD, mean free-to-total PSA ratio and mean PMI (p<0.01, p<0.05, p<0.01, respectively). Benign condition specificities for PM index, percent free PSA, PSA density and total PSA at a 90% sensitivity for prostate cancer were 48%, 10.6%, 8% and 4%, respectively. Of 95 patients, 27 (28.4%) had a PMI of equal or more than 3.1, including 12 of 75 (16%) with negative biopsy and 15 of 20 (75%) with positive biopsy. Furthermore a cutoff MI 0.86 P correctly identified 24% of benign cases without missing any prostate cancer cases. The comparison of receiver operating characteristic (ROC) curve areas showed that PMI was better than total PSA (p<0.01). Although, the area under the ROC curve of % free PSA and PSAD were higher than the area of total PSA, these differences were not statistically significant (p>0.05). Conclusions: We concluded that the prostate malignancy index could be utilized to differentiate benign conditions from prostate cancer in patients with intermediate PSA levels and normal digital rectal examination. Also significant numbers of negative biopsies can be prevented in these patients.