Transition Zone Prostate Specific Antigen Density Research Articles

Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml-1.

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0–10.0 ng ml−1, 10.1–20.0 ng ml−1, and >20.0 ng ml−1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml−2, 0.297 ng ml−2, and 1.180 ng ml−2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.

Comparison of PSA-density of the transition zone and whole gland for risk stratification of men with suspected prostate cancer: A retrospective MRI-cohort study

PurposeTo compare the correlation of transition zone prostate-specific antigen density (TZPSAD) versus whole gland (WG) density (PSAD) with Gleason score. MethodsIn this single-center, retrospective cohort study, men undergoing MRI of the prostate in 2015 and 2016 who had a transperineal template saturation biopsy within 6 months of MRI were included (n = 178; median age 64 y, interquartile range [IQR] 58–68 y; PSA 6.6 ng/ml, 4.6–9.7 ng/ml). The WG and TZ were segmented voxel-wise on T2-weighted transverse planes. The volumes and corresponding PSA-densities were calculated. Correlations with the Gleason score were assessed with Spearman’s rho. Optimal thresholds of the PSA densities were computed using the Youden Index of the receiver-operating-characteristics curve. A p-value of ≤ 0.05 was considered statistically significant. ResultsMedian WG volume was 45 ml (IQR: 33.9–58.7 ml, range: 17.2–165.3 ml), median volume of the TZ was 27.3 ml (IQR: 19.2–39.3 ml, range: 9.0–141.1 ml). Both PSA density values, PSAD and TZPSAD, correlated significantly with the Gleason score: The PSAD (rho = 0.39) showed significantly weaker correlation than the TZPSAD (rho = 0.44, p = 0.05). ROC analysis revealed an ideal cut-off of 0.15 ng/ml2 for PSAD (95%-CI: 0.09–0.16 ng/ml2) and 0.22 ng/ml2 for the TZPSAD (0.15-0.32 ng/ml2) for discrimination between Gleason 3 + 4 and 4 + 3. ConclusionThe TZPSAD exhibited a stronger correlation with cancer dedifferentiation than PSAD and may thus be a better surrogate marker for cancer aggressiveness than PSAD. Moreover, the TZPSAD threshold of 0.22 ng/ml2 may help in risk stratification of men with suspected PCa.

Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

ABSTRACTPurpose:To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 – 10.0 ng/mL and its ability to reduce unnecessary biopsies.Materials and Methods:This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 – 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted.Results:Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0.806) (P<0.001) and PSAD (0.806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies.Conclusions:PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies.

Transition Zone Prostate-specific Antigen Density Could Better Guide the Rebiopsy Strategy in Men With Prostate Inflammation at Initial Biopsy

To assess the role of transition zone prostate-specific antigen density (TZPSAD) in determining rebiopsy strategy in men with prostate inflammation at initial biopsy. Analysis was performed on data derived from transrectal ultrasound-guided prostate biopsy registry containing 2461 men who underwent biopsy between March 2005 and January 2015. Eligible patients were divided into 2 groups based on the presence of chronic inflammation in prostate. Group 1 consisted of 920 patients with histopathologic evidence of chronic inflammation and group 2 consisted of 1287 patients with no evidence of inflammation. Receiver operating characteristic curve analysis was performed to evaluate the accuracy of PSA, PSA density (PSAD), and TZPSAD for detecting prostate cancer (PCa) in each group. Patients who underwent rebiopsy during the study period were further assessed to determine factors that may predict the presence of PCa on subsequent biopsies. In group 1 patients, at 90% sensitivity for detecting PCa, PSAD and TZPSAD showed 19.7% and 37.8% specificity at cutoff values of 0.10 and 0.27 ng/mL/mL respectively, whereas in group 2 patients, PSAD and TZPSAD revealed 29.8% and 31.4% specificity, respectively. Chronic inflammation at initial biopsy was associated with a significant decrease in the likelihood of cancer detection during rebiopsy (odds ratio, 0.42; 95% confidence interval, 0.18-0.99). TZPSAD was found to be capable of sparing 39.8% of unnecessary rebiopsies in group 1 patients, whereas it spared 20.5% of unnecessary rebiopsies in group 2 patients. Applying TZPSAD is advantageous in determining rebiopsy strategy in patients with proven inflammation of prostate at initial biopsy.

Transition zone prostate specific antigen density improves prostate cancer detection in Iranian men.

Background:Prostate specific antigen (PSA) as a tumor marker has extensively changed the diagnosis of prostate cancer (PCa). With the advent of PSA, the majority of patients are diagnosed with nonpalpable early stage PCa. However, PSA lacks specificity and many patients undergo unnecessary biopsies due to an elevated serum PSA level.Objectives:This study aimed to assess the sensitivity and specificity of transition zone PSA density (TZPSAD) in detection of PCa.Patients and Methods:This study was performed on 1712 men underwent trans-rectal ultrasound guided prostate biopsy in our institution between March 2008 and March 2013. A total of 1120 men with PSA < 20 ng/mL and normal digital rectal exam were selected for evaluation. Transition zone PSA density was calculated in all patients and the receiver operating characteristic (ROC) curve was used to analyze the accuracy of TZPSAD for the diagnosis of PCa.Results:Among 1120 men who were eligible for enrolment, prostate cancer was detected in 265 patients. Mean serum PSA levels were 9.7 ± 4.3 ng/mL and 8.5 ± 3.7 ng/mL in patients with and without PCa, respectively (P < 0.001). Mean value for TZPSAD was 1.18 ± 1.19 ng/mL/mL in patients with PCa, whereas it was 0.55 ± 0.84 ng/mL in men without cancer (P < 0.001). Optimal cut-off value for TZPSAD was 0.32 ng/mL. At this cut-off value, the sensitivity and specificity values for TZPSAD were 85% and 45%, respectively. Applying the TZPSAD for PCa screening decreased 50% of unnecessary biopsies.Conclusions:Using TZPSAD as an adjunct to PSA may improve the specificity of PSA in the diagnosis of PCa and decrease the number of unnecessary prostatic biopsies in Iranian men with serum PSA level < 20 ng/mL.

Diagnostic significance of [−2]pro-PSA and prostate dimension-adjusted PSA-related indices in men with total PSA in the 2.0–10.0 ng/mL range

One of the most important issues to address when developing an optimal screening system for prostate cancer is investigating appropriate biopsy indications following serum prostate-specific antigen (PSA) measurements in order to maintain high sensitivity and avoid unnecessary biopsy. Between April 2004 and December 2007, 239 consecutive men with total PSA levels of 2.0-10.0 ng/mL underwent measurements of PSA, free PSA, and [-2]pro-PSA. We assessed the significance of laboratory-based PSA-related indices including free PSA/total PSA (%f-PSA), p2PSA/free PSA (%p2PSA), p2PSA/%f-PSA, Prostate Health Index (phi, an index combining PSA, free PSA, and p2PSA), total prostate volume (TPV)-adjusted PSA-related indices, including PSA density, %p2PSA density, p2PSA/%f-PSA density, and phi density, and transition zone (TZ) prostate volume-adjusted PSA-related indices such as PSA TZ density (PSATZD), %p2PSA TZD, p2PSA/%fPSA TZD, and phi TZD. The positive biopsy rate was 22.2%. When sensitivity was fixed at 95 %, unnecessary biopsies could be avoided in 28% of men when phi was used as a biopsy indication. In cases where total and transition zone prostate volumes were available, the use of %p2PSA density, phi density, p2PSA/%f-PSA TZD, and phi TZD resulted in the avoidance of 48, 47, 54, and 54 % of unnecessary biopsies, respectively, while maintaining a high sensitivity of 90%. At 90 and 95 % sensitivity, laboratory-based indices containing p2PSA, particularly phi, showed significantly greater specificity for prostate cancer as compared with %f-PSA. The diagnostic accuracy of prostate volume-adjusted p2PSA-related indices could be excellent, particularly the transition zone volume-adjusted indices at fixed sensitivities of 95 and 90%.

Relationship between Chronic Inflammation at Prostate Biopsy and Transition Zone Prostate Volume Enlargement in a Prospectively UK Screened Population

Objective: The aim of this study was to evaluate the relationship between histological prostatic inflammation and prostate volume at the time of prostate biopsy. Patients and methods: From a prospective prostate cancer screening study, 137 men aged 50–65 years, underwent prostate biopsies negative for cancer, forming the study population. Biopsy criteria were prostate specific antigen (PSA) &gt;4 ng/ml ( n = 40), or between 1.1 and 4ng/ml with a percent free PSA (%fPSA) &lt;25% ( n = 97). Total gland (TG) and transition zone (TZ) volumes were measured prior to TRUS guided biopsy. Histological classification included chronic inflammation (CIlymphocyte predominant), active inflammation (AI-neutrophil predominant), and benign prostatic tissue (BPT-no inflammatory cells). A logistic regression analysis was performed using age, TPSA, %fPSA, histology, TZ and TG volume, TZ/TG ratio, PSA density, and transition zone PSA density as continuous variables. We also mailed validated self-administered symptom scores to men in the three histological subgroups (men without cancer) at a median of follow up of 6.5 years (range 5.9–7.1 years) after screening and biopsy. Results: Histological chronic inflammation ( n = 78, 57%) at biopsy was associated with a larger mean TG volume (30.8cc) than active inflammation ( n =7, 22.7cc) and benign prostatic tissue ( n = 52, 25.9cc). On bivariate analysis, chronic inflammation was associated with greater TZ volume ( p = 0.0015) and TZ/TG ratio ( p = 0.0008). On multivariate analysis, chronic inflammation was the only independent variable associated with a greater ratio of the TZ to TG volume (odds ratio 478, p = 0.005). IPPS symptoms scores were completed and returned by 88 men (66% compliance). In men with chronic inflammation (49), active inflammation (5), and benign tissue (30), the mean IPSS scores were 10.9, 7.2, and 8.7, respectively. These differences did not reach statistical significance p &gt; 0.05. Conclusions: In this younger screened population, chronic inflammation was associated with greater prostate gland volume secondary to transition zone volume enlargement. Further research is needed to establish a causally related link for this observation.

Utility of the transition zone index for identification of prostate cancer in Chinese men with intermediate PSA levels

We aimed to investigate the utility of the transition zone index (TZI) for identification of prostate cancer (PCa) in Chinese men with prostate-specific antigen (PSA) levels of 4-10 ng/mL. In this retrospective cohort study, results of transrectal ultrasonography (TRUS)-guided biopsy were assessed in 616 consecutive Chinese men; all subjects had intermediate serum PSA levels and normal digital rectal examination findings. The prostate and transition zone volumes were determined by TRUS. A TZI cutoff value of 0.47 produced the best sensitivity and specificity rates in receiver operating characteristic (ROC) curve analysis and thus was used to classify the study subjects into two subgroups: group 1 with TZI ≤ 0.47 and group 2 with TZI > 0.47. Logistic regression analysis was used to predict outcomes. The variables that were statistically significant in the stepwise logistic regression analysis were assessed using the ROC curve and the area under the curve. Overall, 166 of the 616 patients (26.9%) had histologically confirmed PCa. A total of 238 (38.6%) patients were classified into group 1, of whom 97 (40.8%) exhibited a positive biopsy; and 378 (61.4%) patients were classified into group 2, of whom 69 (18.3%) exhibited a positive biopsy. The stepwise logistic regression analysis revealed that PSA density (PSAD) exhibited the strongest predictive value in the overall population and in group 1, whereas PSA transition zone density (PSATZD) was the optimal predictor in group 2. The ROC curve analysis revealed that when using the TZI-specific 100% sensitivity cutoffs, 17.7% and 25% of the biopsies were unnecessary and could be avoided in the overall patient population prior to and following the division into groups, respectively (P = 0.002). Using an individually generated 95% sensitivity cutoff of 0.12 ng/mL(2) for PSAD and a cutoff of 0.179 ng/mL(2) for PSATZD for TZI-stratified cohorts of TZI ≤ 0.47 and TZI > 0.47, a more consistent specificity of 44% and 46.9%, respectively, for each cohort was observed. The optimal predictor for PCa differs between various TZI levels. The combination of PSAD in patients with TZI ≤ 0.47 and PSATZD in patients with TZI > 0.47 helps to identify potentially unnecessary biopsies compared to the use of a single PSAD for the entire patient population. The discrepancies regarding an optimal predictor in published reports are most likely due to the differing TZI levels among the cases. In this study, we demonstrated improved identification of PCa using TZI-adjusted cutoffs for PSAD and PSATZD.

Transition zone PSA density improves the prostate cancer detection rate both in PSA 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men

ObjectivesWe hypothesized the prostate-specific antigen (PSA) “grey zone” in Chinese men was higher than the traditional value (4.0–10.0 ng/ml) since incidence of prostate cancer (CaP) in Chinese men was relative low. We then assessed the efficiencies of transition zone PSA density (TZPSAD) in the diagnosis of CaP in Chinese men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml. Materials and methodsMen had a prostatic biopsy for detecting CaP from November 1999 to August 2009 were retrospectively retrieved from our computer center. Those had a document of transrectal ultrasound transition zone measurement with a PSA of 4.0–20.0 ng/ml were included. Receiver-operating characteristic (ROC) curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of CaP. ResultsA total of 189 men were included in the study. Of these men, 78 and 111 had a PSA of 4.0–10.0 and 10.1–20.0 ng/ml, respectively. The rate of CaP in men with a PSA of 4.0–10.0 ng/ml was not statistically significantly different compared with those with a PSA of 10.1–20.0 ng/ml (20.5% vs. 21.6%, P = 0.854). The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were 0.569 and 0.702 in men with a PSA of 4.0–10.0 ng/ml and 0.463 and 0.730 in men with a PSA of 10.1–20.0 ng/ml, respectively. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 4.0–10.0 ng/ml was 0.370 ng/ml/ml, the sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 10.1–20.0 ng/ml was 0.500 ng/ml/ml. Its sensitivity equaled 70.8%, specificity 70.1%. ConclusionsUsing TZPSAD can improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary prostatic biopsy in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men.

Clinical Predictive Factors in Patients with Prostate Cancer Diagnosed by Repeat Prostate Biopsy

Purpose: We investigated the predictive factors in patient with prostate cancer diagnosed by repeat prostate biopsy, where initial prostate biopsy results were negative for malignancy. Materials and Methods: Between March 2000 and June 2007, 1280 men with suspected prostatic cancer underwent transrectal ultrasound guided needle biopsy of the prostate, with 148 (11.6%) diagnosed as having prostate cancer. Of 1132 men whose biopsy results were negative for malignancy, 655 whose prostate specific antigen (PSA) was elevated persistently underwent second biopsy, and 462 underwent third biopsy as the same course. Twelve core biopsies were performed in the majority of patients. To determine predictive factors, we evaluated prostate volume, serum PSA, percent free PSA, PSA density (PSAD), transition zone PSAD, PSA velocity (PSAV) and pathological report of previous biopsy between the men with cancer detection and the men with negative biopsy in second and third biopsy. Results: Overall cancer detection rate was 16.3% (208/1280). From the first, second and third biopsies, the cancer detection rate were 11.6, 5.5 and 5.2%, respectively. There were significant differences in percent free PSA, transition zone PSAD, PSAV between cancer and negative biopsy groups after serial repeat biopsies (p<0.05). Multivariate logistic regression analysis revealed that the transition zone PSAD, PSAV, and presence of either atypical small acinar proliferation (ASAP) or high grade prostatic intraepithelial neoplasia (HGPIN) in initial biopsy specimen were significant predictors for prostate cancer diagnosed by repeat biopsy. Conclusions: Of the men with negative results on the first biopsy, 60 (5.4%) were diagnosed prostate cancer after serial biopsies. The transition zone PSAD, PSAV, and presence of either ASAP or HGPIN in initial biopsy specimen are predictable factors for prostate cancer detection on repeat biopsy. 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

PSA Doubling Time as a Predictive Factor on Repeat Biopsy for Detection of Prostate Cancer

Detection of prostate cancer needs a biopsy of the prostate. Suspecting cancer from an increase in prostate-specific antigen (PSA) has a high negative rate at an initial prostate biopsy. Cases with negative initial biopsy may be the candidates of subsequent biopsy. For lowering unnecessary repeat biopsy, the use of predictive factors before a repeat biopsy is applied for indication. Seventy-seven cases with negative initial prostate biopsy received a repeat biopsy and factors for the detection of cancer were examined. PSA doubling time distinguished a part of cancer cases. Its sensitivity of 30, 50 and 70 months was 36.6%, 30.4% and 10%, respectively. Cancer case did not show PSA doubling time of >100 months in general. Values of PSA transition zone density, %Free/total PSA and PSA velocity were similar between cancer and no cancer cases. PSA doubling time was one of the predictive factors for the detection of prostate cancer and was valuable for avoiding unnecessary repeat biopsy in some cases.

Update on Prostate-Specific Antigen Testing for the Early Detection of Prostate Cancer

The introduction of prostate-specific antigen (PSA) has revolutionized the detection and management of men with prostate cancer (PCa). This review discusses the clinically useful risk factors associated with the development of PCa and the salient features of PSA. It will help to highlight the abilities and limitations of PSA with respect to the diagnosis and management of PCa. Emphasis will be placed on the factors affecting serum total PSA (tPSA) levels, the optimal cutoff values, the use of calculated parameters such as PSA density, PSA transition zone density, PSA velocity, age- and racespecific PSA ranges, and the various molecular forms. There is an imminent need for novel biomarkers that can improve specificity for PCa, allow accurate classification of clinically insignificant PCa, allow for detection of clinically significant PCa in patients without elevated serum PSA, and allow for the identification of aggressive forms of PCa, which may warrant adjunctive or even molecularly targeted therapy in the future. Upon completion of this exercise, readers should be able to identify risk factors for prostate cancer (PCa) and assess their impact on the thresholds of serum tPSA levels with respect to optimal performance in detecting PCa; define the ideal age to begin screening for PCa in men possessing highrisk characteristics; understand factors other than PCa affecting serum tPSA levels and assess their impact on the thresholds of serum tPSA levels with respect to optimal performance in the detection of PCa; and discuss the diagnostic performance of lower thresholds for serum tPSA testing in screening for and in diagnosing PCa.

Comparison between PSA density, free PSA percentage and PSA density in the transition zone in the detection of prostate cancer in patients with serum PSA between 4 and 10 ng/ml

Compare the capacity of the PSA density (PSAD), Free PSA percentage (%FPSA) and PSA transition zone density (PSATZ) in improving the sensitivity and specificity of the PSA to detect prostate cancer (PCa) in men with a PSA between 4 and 10 ng/mL. One hundred and forty five men with PSA between 4 and 10 ng/mL were prospectively studied. Blood collection for the total PSA and free PSA was performed as well as transrectal ultra-sound with prostate biopsy and measurement of the total prostate volume (TPV) and transition zone volume (TZV). Patients with initial negative biopsy were followed and the prostate biopsy was repeated in those that presented PSA increase. The capacity of the PSAD, %FPSA and PSADTZ in improving the sensitivity and specificity pf the PSA test to the detection of the PCa was assessed by univariate and multivariate analyses and through the ROC curve. Of the 145 patients, 38 (26.2%) had PCa and in 107 (73.8%) a benign prostate disease was diagnosed. No difference among the PSAD, %FPSA and PSADTZ was found. The multivariate analysis showed that the PSADTZ, %FPSA, TZV and age were those more powerful and highly significant PCa predictors. The determination of %FPSA and PSAD can allow a better discrimination between PCa and benign disease that the isolated use of PSA. The combination of PSADTZ, %FPSA, TZV and age promote a high accuracy for PCa detection.

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.

PREDICTORS OF PROSTATE CANCER EVALUATED BY RECEIVER OPERATING CHARACTERISTICS PARTIAL AREA INDEX: A PROSPECTIVE INSTITUTIONAL STUDY

To our knowledge we introduce the ROC partial area under the curve (AUC) index as a method of evaluating the discriminative power of different prostate cancer predictors. Peripheral zone volume and peripheral zone prostate specific antigen (PSA) density are introduced as potential predictors and compared with other known predictors of prostate cancer. During 1999, 220 consecutive patients with suspected early prostate cancer were examined using total PSA, free PSA, total prostate volume, transition zone volume and transrectal ultrasonography guided sextant biopsy of the prostate. The free-to-total PSA ratio, PSA density, transition zone PSA density, peripheral zone volume and peripheral zone PSA density were calculated. Usually total AUC is used to evaluate the discriminative power of different parameters. In this study parameters were evaluated by the ROC partial area index, which includes only the AUC in highly sensitivity parts of the ROC curve. Explorative analysis using logistic regression analysis was performed to investigate the ability of combinations of parameters to predict cancer. Of the 220 patients 75 were diagnosed with cancer. In the subgroup of 160 patients with PSA less than 10 microg/l 44 had cancer. Transition zone PSA density and PSA density had significant discriminative power in the total group, while none of the parameters were discriminative in the subgroup of patients. When high sensitivity is demanded, the ROC partial area index seems to be meaningful for evaluating the discriminative power of potential predictors. In our study none of the evaluated parameters had discriminative power in patients with PSA less than 10 microg/l, while transition zone PSA density and PSA density showed discriminative power in the total group of patients.

The Use of Artificial Neural Network Analysis to Improve the Predictive Accuracy of Prostate Biopsy in the Japanese Population

We examined the efficacy of an artificial neural network analysis (ANNA) based on parameters available from previously existing examinations for improving the predictive accuracy of prostate cancer screening in the Japanese population. Two hundred and twenty-eight patients with prostate-specific antigen (PSA) of 2-10 ng/ml were enrolled in this study. Two artificial neural network analysis (ANNA) models were constructed: ANNA1 with patient age, total PSA, free to total PSA ratio, prostate volume, transition zone volume (TZ), PSA density (PSAD) and PSA-TZ density (PSATZ) as input variables, and ANNA2 with presumed circle area ratio (PCAR), digital rectal examination (DRE) findings and chief complaint added as variables. The predictive accuracies of the ANNA models were compared with conventional PSA and volume-related parameters and a logistic regression (LR) model by receiver operating characteristic (ROC) curve analysis. Of 228 patients, 58 (25.5%) were diagnosed with prostate cancer. While ANNA2 had a slightly larger area under the curve (AUC) than ANNA1 (0.782 versus 0.793, P = 0.8477), the AUC of ANNA2 was significantly greater than those of ln(PSA), PSAD, PSATZ and free to total PSA ratio (P = 0.0004, 0.0230, 0.0304, and 0.0037, respectively). The accuracy of ANNA2 was significantly better than that of LR analysis at 90 and 95% sensitivity levels (P = 0.0051 and P < 0.0001, respectively). At 95% sensitivity level, ANNA2 reduced unnecessary biopsies by 40.0% with a negative predictive value of 95.7%. To determine the indication of prostate biopsy for PSA value in the range of 2-10 ng/ml, the ANNA model has the possibility to reduce unnecessary biopsies without missing many cases of cancers.

Predictors of Prostate Cancer After Initial Negative Systematic 12 Core Biopsy

We determined the cancer detection rate at initial systematic 12 core (S12C) biopsy and identified features associated with cancer at repeat S12C biopsy after an initial negative S12C biopsy in patients with prostate specific antigen (PSA) parameters associated with a higher risk of prostate cancer. Between February 1999 and June 2002, 841 patients underwent initial S12C biopsy. Of these patients 99 underwent repeat S12C biopsy after initial negative S12C because of a percent free-to-total PSA of 15.0 or less and/or a yearly PSA velocity of 0.75 ng/ml or greater. The association between parameters revealed by initial biopsy and cancer at repeat biopsy was assessed. Of the 99 patients 21 (21.2%) had cancer at repeat biopsy. Age (p = 0.01), PSA transitional zone density (p = 0.05), and high grade PIN at initial biopsy (p = 0.01) were associated with cancer at repeat biopsy. In this select group of patients with PSA parameters associated with a higher risk of prostate cancer the cancer detection rate after initially negative S12C biopsy was 21%. Patients with high grade PIN on initial biopsy, advanced age and higher PSA transition zone density are at increased risk for cancer at repeat biopsy. Larger prospective studies are required to confirm these results and construct a nomogram that determines the probability of finding prostate cancer at subsequent biopsy.

Clinical, biochemical and pathological features of initial and repeat transrectal ultrasonography prostate biopsy positive patients.

Using sextant biopsy, 16-41% of prostate cancers were diagnosed on repeat biopsy. The objective of the present study was to compare the differences in the clinical, biochemical and pathological features between patients with positive results on initial and repeat biopsies, with an aim to identify factors that can be used to improve the detection rate of transrectal ultrasound (TRUS) biopsy of the prostate. Between February 2000 and April 2001, 222 patients with a mean age of 64 years (range 38-85) underwent TRUS-guided 10-core prostate biopsy for either abnormal prostate specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination (DRE). Of this number, 165 patients underwent their first biopsy, whereas 45 and 12 patients had had one or two previous biopsies, respectively. Prostate cancer detection rates for the initial biopsy group (n = 165), second biopsy group (n = 45) and third biopsy group (n = 12) were 29.7, 23.0 and 41.7%, respectively. Six patients who had a negative first 10-core biopsy underwent a second 10-core biopsy and one patient (16%) was found to have cancer. Apart from total prostate volume, there were no significant statistical differences between the patient age, mean total PSA, PSA density, PSA-transition zone density, DRE and TRUS findings between the initial and repeat biopsy groups of subjects who had cancer. Those who had cancer detected only on repeat biopsies had larger prostate glands (P = 0.041). Patients who had cancer detected only on repeat biopsies had bigger prostate glands, supporting the hypothesis that TRUS sextant biopsy as a technique suffers the error of under-sampling in a bigger prostate.

Prediction of extraprostatic cancer by prostate specific antigen density, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

The present study was designed to identify the preoperative parameters, including PSA-based parameters, and endorectal MRI, predictive of pathological stage in males who underwent radical prostatectomy. We studied 114 patients who underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized prostate cancer. Clinical stage was assessed by DRE, pelvic CT scan, endorectal MRI, and bone scan. The correlation between the preoperative parameters, including PSA-based parameters, clinical stage, and histological findings of biopsy specimens, and the pathological stage was analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for local extent of disease. Seventy-six (66.6%) patients had organ confined cancer and 38 (33.4%) patients had extraprostatic cancer. Of the 38 patients with extraprostatic cancer, four had seminal vesicle involvement, while, none had pelvic lymph node involvement. Biopsy Gleason score, PSA, PSA-alpha1-antichymotrypsin (PSA-ACT), PSA-density (PSAD), PSA-transition zone density, PSA-ACT density, and PSA-ACT transition zone (TZ) density were significantly higher and percent free PSA was lower in the patients with organ confined cancer than those with extraprostatic cancer (P < 0.01). PSAD showed the largest area under the ROC curve (AUC) among those parameters (AUC = 0.732). Sixty-eight (74.7%) of 91 patients with T2 on endorectal MRI had organ confined cancer, while 15 (65.2%) of 23 patients with T3 had extraprostatic cancer (P < 0.01). Multivariate logistic regression analysis indicated that Gleason score (> or =7 vs. < or =6), endorectal MRI findings, and PSAD were significant predictors of extraprostatic cancer (P < 0.01). The present study demonstrated that preoperative PSAD was the most valuable predictor among PSA-based parameters for extraprostatic disease in patients with clinically localized prostate cancer. The combination of PSAD, endorectal MRI findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

An Artificial Neural Network for Prostate Cancer Staging when Serum Prostate Specific Antigen is 10 NG./ML. or Less

An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p <0.01). The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.