Intermediate Prostate-specific Antigen Research Articles

A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer

ObjectiveThe relationship between prostate-specific antigen (PSA) and prostate cancer (PCa) grade was traditionally thought to be linear but recent reports suggest this is not true in high-grade cancers. We aimed to compare the association between PSA and PCa-specific mortality (PCSM) in clinically localised low/intermediate and high-grade PCa. Subjects/patients and methodsRetrospective cohort study using the National Prostate Cancer Audit database in England of men treated with external beam radiotherapy (EBRT), EBRT and brachytherapy boost (EBRT + BT), radical prostatectomy or no radical local treatment between 2014 and 2018. Multivariable competing-risk regression was used to examine the association between PSA, Gleason, and PCSM. Multivariable restricted cubic spline regression was used to explore the non-linear associations of PSA and PCSM. Results102,089 men were included, of whom 71,138 had low/intermediate-grade and 22,425 had high-grade PCa. In high-grade, 4-year PCSM was higher with PSA ≤5 than PSA 5.1–10 for men treated with EBRT (hazard ratio 1.96 (95% confidence interval 1.15–3.34) or no radical local treatment (hazard ratio 1.99 (95% confidence interval 1.33–2.98). Restricted cubic spline regression showed that PSA and PCSM have a non-linear association in high-grade but a linear association in low/intermediate-grade PCa. ConclusionThe low-PSA/high-grade combination in M0 PCa treated with EBRT has a higher PCSM than those with high-grade and intermediate PSA levels. In high-grade disease, the PSA association was non-linear; by contrast, low/intermediate-grade had a linear relationship. This confirms a more aggressive biology in low PSA secreting high-grade PCa and a worse outcome following treatment.

Absolute Prostate Specific Antigen after 6 Months of Androgen Deprivation Therapy Is a Predictor of Overall and Cancer-Specific Mortality in Men with Hormone-Sensitive Prostate Cancer.

We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

PD65-07 LIFESTYLE MODIFICATIONS AND THEIR EFFECT ON SERUM PROSTATE SPECIFIC ANTIGEN LEVELS

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-07 LIFESTYLE MODIFICATIONS AND THEIR EFFECT ON SERUM PROSTATE SPECIFIC ANTIGEN LEVELS Alexandre R. Zlotta, Jimmy Misurka, Katherine Lajkosz, Andrea Mari, Serena Marzario, Cynthia Kuk, Sophie O’Halloran, Alex Zisman, Annette Erlich, Michael Nesbitt, Dhiral Kot, Rob Hamilton, Girish Kulkarni, Nathan Perlis, Anto Finelli, Sigrid Carlsson, and Neil Fleshner Alexandre R. ZlottaAlexandre R. Zlotta More articles by this author , Jimmy MisurkaJimmy Misurka More articles by this author , Katherine LajkoszKatherine Lajkosz More articles by this author , Andrea MariAndrea Mari More articles by this author , Serena MarzarioSerena Marzario More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Sophie O’HalloranSophie O’Halloran More articles by this author , Alex ZismanAlex Zisman More articles by this author , Annette ErlichAnnette Erlich More articles by this author , Michael NesbittMichael Nesbitt More articles by this author , Dhiral KotDhiral Kot More articles by this author , Rob HamiltonRob Hamilton More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , Nathan PerlisNathan Perlis More articles by this author , Anto FinelliAnto Finelli More articles by this author , Sigrid CarlssonSigrid Carlsson More articles by this author , and Neil FleshnerNeil Fleshner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Guidelines recommend to repeat serum Prostate Specific Antigen (PSA) measurement to confirm an elevated value before proceeding with further testing. The effect of diet and lifestyle on repeat PSA levels to minimize false positives has rarely been examined. We aimed here to explore the effects of dietary and lifestyle changes on serum PSA values in men with intermediate PSA levels and normal digital rectal examination (DRE). METHODS: We used a case-control design including 204 men with PSA levels between 2-10ng/ml. 82 men who followed lifestyle changes (intervention group) were matched with 122 men (control group), who did not undergo any lifestyle modifications (avoiding spicy foods, alcohol, caffeine consumption and biking) before repeat PSA. PSA changes between baseline and repeat measurement were compared between the intervention group and controls using the Mann-Whitney U test. Multivariable logistic regression models were used to assess differences in PSA changes below different pre-determined thresholds. Linear mixed models implemented for changes in PSA as a continuous covariate helped visualize the predicted change in PSA from baseline. RESULTS: Age (61.0 vs 60.3 years), prostate volume (52.3 vs 49.0 cc) and PSA levels at baseline (5.83 vs 5.75 ng/ml) in the control and intervention arm, respectively, were not different. Compared to controls, at a median 2.81 months interval (IQR: 1.69-4.61), men in the intervention arm had a significantly lower total PSA on repeat PSA testing (4.14 vs 5.32ng/ml, p<0.001). Lifestyle changes resulted in PSA levels dropping below 4ng/ml in 40% of men with initial PSA 4-10 ng/ml in the intervention group vs 22% in controls (p=0.02). In the 2-4ng/ml range, 45% of men in the intervention group vs 14% in controls had their repeat PSA <2ng/ml (p=0.02). Intervention was an independent predictor of repeat PSA dropping <3ng/ml for men with baseline PSA of 3-10ng/ml (OR 5.39, 95% CI 1.96, 14.8, p=0.001). Limitations include the retrospective design of the study, absence of use of metrics to measure adherence to recommendations and lack of cycling information. CONCLUSIONS: In men with intermediate PSA levels and negative DRE, dietary and lifestyle modifications decrease serum PSA values more, and in a larger proportion than simply repeating the test. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1154-e1154 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandre R. Zlotta More articles by this author Jimmy Misurka More articles by this author Katherine Lajkosz More articles by this author Andrea Mari More articles by this author Serena Marzario More articles by this author Cynthia Kuk More articles by this author Sophie O’Halloran More articles by this author Alex Zisman More articles by this author Annette Erlich More articles by this author Michael Nesbitt More articles by this author Dhiral Kot More articles by this author Rob Hamilton More articles by this author Girish Kulkarni More articles by this author Nathan Perlis More articles by this author Anto Finelli More articles by this author Sigrid Carlsson More articles by this author Neil Fleshner More articles by this author Expand All Advertisement Loading ...

PCN166 Comparative Effectiveness and Cost-Effectiveness of Reflex Testing Men with Intermediate PSA Levels: A Systematic Model-Based Analysis

For asymptomatic men with intermediate prostate-specific antigen (PSA) levels concerned about prostate cancer (PCa), many reflex tests are available to guide decisions around prostate biopsy. This study aimed to systematically evaluate the impact of incremental performance improvements on the comparative effectiveness and cost-effectiveness of these tests.

Economic Evaluation of Urine-Based or Magnetic Resonance Imaging Reflex Tests in Men With Intermediate Prostate-Specific Antigen Levels in the United States

ObjectivesFor men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States. MethodsWe used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers—PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)—were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies. ResultsBiopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively. ConclusionsUsing PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.

Role of 68Ga-PSMA-PET/CT for the detection of primary prostate cancer prior to biopsy: a prospective study.

IntroductionProstate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET-CT) is widely used as a staging tool for patients with prostate cancer (PCa). The objective of the study is to assess the diagnostic accuracy of 68Ga-PSMA-PET/CT for PCa, which may help us avoid unnecessary biopsies in patients with intermediate prostate-specific antigen (PSA) levels.Material and methodsIn this prospective study, 81 patients suspected of PCa, with either raised PSA between 4–20 ng/ml or abnormal digital rectal examination (DRE) findings were included. 68Ga-PSMA-PET/CT was performed for all patients followed by transrectal ultrasound (TRUS) guided prostate biopsy. SUVmax (maximum standardized uptake value) was measured and correlated with biopsy results.ResultsOut of 81 patients, 31 (38.3%) patients were found to have malignancy on biopsy. Median SUVmax of biopsy positive patients was 10.4 (IQR 6.5–16.1) and biopsy negative patients (n=50) was 3.5 (IQR 1–4.9), (p <0.001). At a cut-off of 6.15, 68GA-PSMA-PET/CT demonstrated sensitivity of 84%, specificity of 80%, positive predictive value of 72.2%, negative predictive value of 88.9% and accuracy of 81.5% with an AUC of 0.876 (95% CI: 0.799–0.953, p <0.001).ConclusionsThe 68Ga-PSMA-PET/CT helps to localize suspicious lesions and improving the detection of primary prostate cancer. Our findings indicate a significant correlation of SUVmax values with biopsy results. We were also able to determine a cut-off value of SUVmax below which prostate biopsy can be avoided in selected patients.

Overdiagnosis and Lives Saved by Reflex Testing Men With Intermediate Prostate-Specific Antigen Levels.

Several prostate cancer (PCa) early-detection biomarkers are available for reflex testing in men with intermediate prostate-specific antigen (PSA) levels. Studies of these biomarkers typically provide information about diagnostic performance but not about overdiagnosis and lives saved, the primary drivers of associated harm and benefit. We projected overdiagnoses and lives saved using an established microsimulation model of PCa incidence and mortality with screening and treatment efficacy based on randomized trials. We used this framework to evaluate four urinary reflex biomarkers (measured in 1112 men presenting for prostate biopsy at 10 US academic or community clinics) and two hypothetical ideal biomarkers (with 100% sensitivity or specificity for any or for high-grade PCa) at one-time screening tests at ages 55 and 65 years. Compared with biopsying all men with elevated PSA, reflex testing reduced overdiagnoses (range across ages and biomarkers = 8.8-60.6%) but also reduced lives saved (by 7.3-64.9%), producing similar overdiagnoses per life saved. The ideal biomarker for high-grade disease improved this ratio (by 35.2% at age 55 years and 42.0% at age 65 years). Results were similar under continued screening for men not diagnosed at age 55 years, but the ideal biomarker for high-grade disease produced smaller incremental improvement. Modeling is a useful tool for projecting the implications of using reflex biomarkers for long-term PCa outcomes. Under simplified conditions, reflex testing with urinary biomarkers is expected to reduce overdiagnoses but also produce commensurate reductions in lives saved. Reflex testing that accurately identifies high-grade PCa could improve the net benefit of screening.

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.

Psychological impact of serial prostate-specific antigen tests in Japanese men waiting for prostate biopsy.

It is common to repeat prostate-specific antigen (PSA) measurements for men with intermediate PSA elevation before prostate biopsy. In this scenario, men with persistently elevated PSA values may have considerable psychological distress. We attempted to determine whether elevated PSA values have psychological effects on these men in association with the timing of measurement, PSA kinetics, and biopsy results. In order to investigate the initial and late effects of PSA tests on psychological distress during serial measurements, two groups of men with screen-positive results (PSA≥3ng/ml) were studied-205 men whose first questionnaires regarding anxiety and depression were taken at initial screening (group A), and 103 men whose questionnaires were taken at repeated measurement for prior PSA elevation (group B). The level of distress was generally low. There were no significant differences in distress between the two groups, suggesting a constant psychological effect by elevated PSA values over a long period of time. The distress of men in group A increased significantly as PSA levels rose and decreased when they fell to normal range. On the other hand, the distress of men in group B did not change regardless of PSA kinetics, indicating that their psychological condition seemed susceptible to subtle PSA change only in the initial phase of measurements. Unexpectedly, men with benign results showed insignificant but higher distress after prostate biopsy. Although a small fraction of men have psychological distress caused by changes in PSA levels, the benefits, risks (psychological and physical), and limitations of PSA tests must be adequately explained to the patients before entering the screening program.

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible foractive surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml.

Additional Midline Biopsies of the Peripheral Zone Associated with the First Endorectal Standard Sextant Pattern Improves the Accuracy of Prostate Cancer Detection in Japanese Patients

Objectives: This study was designed to estimate the improved accuracy of prostate cancer (PCa) detection resulting from additional midline biopsies of the peripheral zone in first standard biopsy. Patients and Methods: Patients were classified into 3 groups: 402 cases of sextant biopsies (1995-2002), 488 cases of 8-core biopsies with 2 additional midline biopsies (2003-2006), and 391 cases of 10-core biopsies with 4 additional midline biopsies (2007-2012). The positive rate of each number of biopsies and changes in positive rates associated with prostate specific antigen (PSA) ranges were estimated. Results: The positive rate of core biopsy significantly improved with increasing numbers of core biopsies (30.1% for sextant, 43.4% for 8-core biopsies, and 53.1% for 10-core biopsies). The accuracy of biopsies for each PSA range also significantly improved (22.3% for sextant, 30.0% for 8-core biopsies, and 43.2% for 10-core biopsies in the PSA gray zone [4.01-10 ng/ml]; and 26.5% for sextant, 52.9% for 8-core biopsies, and 71.8% for 10-core biopsies in the intermediate PSA range [10.1-20 ng/ml]). In the 208 cases with positive results using the 10-core biopsy method, the distribution of Gleason scores did not differ between the sextant only group and the midline site only group. Conclusions: Additional midline biopsy was associated with improved accuracy of positive core biopsies in Japanese patients with a PSA range of 4.01-20 ng/ml.

Novel Prostate Cancer Biomarkers Derived from Autoantibody Signatures

BACKGROUND: Due to the low specificity of the prostate-specific antigen (PSA) assay and a high false positive rate, a large number of prostate cancer (PCA) biopsies are performed unnecessarily. Consequently, there is a need for new biomarkers that can identify PCA at any stage of progression while limiting the number of false positives. The use of autoantibody signature–developed biomarkers has proven to be an effective method to solve this problem. RESULTS: Using T7 phage–peptide detection, we identified a panel of eight biomarkers for PCA on a training set. The estimated receiver-operating characteristic (ROC) curve had an area under the ROC curve of 0.69 when applied to the validation set. Spearman correlations were high, within 0.7 to 0.9, indicating that the biomarkers have a degree of inter-relatedness. The identified biomarkers play a role in processes such as androgen response regulation and cellular structural integrity and are proteins that are thought to play a role in prostate tumorigenesis. CONCLUSIONS: Autoantibodies against PCA can be developed as biomarkers for detecting PCA. The scores from the algorithm developed here can be used to indicate a relative high or low risk of PCA, particularly for patients with intermediate (4.0 to 10 ng/ml) PSA levels. Since most commercially available assays test for PSA or have a PSA component, this novel approach has the potential to improve diagnosis of PCA using a biologic measure independent of PSA.

Long-term survival of extremely advanced prostate cancer patients diagnosed with prostate-specific antigen over 500 ng/ml.

To investigate survival of hormone-naïve prostate cancer patients diagnosed with prostate-specific antigen ≥500 ng/ml, stratified according to the prostate-specific antigen level and type of therapy. Data of prostate cancer patients with prostate-specific antigen ≥500 ng/ml diagnosed between 2001 and 2003 and receiving primary androgen deprivation therapy were extracted from the Japan Study Group of Prostate Cancer database. Cancer-specific survival and overall survival were assessed according to the prostate-specific antigen level (500-999, 1000-4999 and ≥5000 ng/ml) and type of therapy using Kaplan-Meier analyses and multivariate Cox proportional hazards models including age, Gleason score, oncological stage and comorbidity. The median follow-up was 27 months (interquartile range, 13-51) and a total of 1961 patients were included. Five-year cancer-specific and overall mortalities were 39.0 and 33.0%, respectively. There was a significant inverse relationship between overall survival and prostate-specific antigen magnitude among combination therapy patients, but not monotherapy patients (log-rank test, P = 0.034 and 0.558, respectively). The median overall survival in combination therapy patients with low-, intermediate- and high prostate-specific antigen and monotherapy patients with any prostate-specific antigen were 79, 59, 45 and 43 months, respectively. Multivariate analysis showed that combination therapy in patients with low- and intermediate prostate-specific antigen was significantly associated with a favorable overall survival compared with monotherapy (hazard ratios 0.66 and 0.75, respectively, both P < 0.001). Similar results were obtained for cancer-specific survival. There are major survival differences in extremely high prostate-specific antigen cases according to the prostate-specific antigen level and hormone therapy type and those patients would benefit notably from combination androgen blockade.

The value of percentage free prostate specific antigen (PSA) in the detection of prostate cancer among patients with intermediate levels of total PSA (4.0–10.0 ng/mL) in Nigeria

ObjectivesTo assess the value of percentage free prostate-specific antigen (%fPSA) in the detection of prostate cancer among Nigerian men with an intermediate total PSA level (4–10ng/mL), and to show if the optimum threshold for biopsy is different from Caucasian values when the widely used (six-core, digitally directed) prostate biopsy protocol in Nigerians is applied. Patients and methodsThe study included 105 patients aged >50years, with a palpably benign prostate gland and intermediate levels of total PSA (4–10ng/mL). These patients had a free PSA assay and a transrectal digitally directed six-core biopsy of the prostate. The %fPSA was calculated and the optimum threshold value for detecting prostate cancer was determined. ResultsThe mean (SD) age of the patients was 64.4 (6.6) years and their mean (SD) total PSA level was 6.6 (1.7)ng/mL. Of these men 14 (13.3%) had cancer of the prostate detected by the prostate biopsy. The %fPSA level related directly to sensitivity values but inversely to the specificity and the positive predictive values. The best threshold of %fPSA for detecting cancer in these men was <40%, with a sensitivity of 100%, specificity of 93.4% and a positive predictive value of 70% (P<0.05). ConclusionsIn evaluating Nigerian patients with a palpably benign prostate gland and within the intermediate total PSA range, when digitally directed biopsy protocol is adopted, a %fPSA threshold of <40% will detect significant percentage of those with prostate cancer, with a minimal number of unnecessary biopsies. This value differs from that reported in western studies in which transrectal ultrasonography-directed biopsy was used.

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.

Risk of prostate cancer after detection of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on extended core needle biopsy: a UK hospital experience

BackgroundHigh-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor lesion to prostate cancer (CaP). UK-based studies examining the occurrence of isolated HGPIN and subsequent risk of CaP are lacking. Our aim was to assess the occurrence of HGPIN in a regional UK population and to determine whether in a retrievable cohort of such patients that had repeat extended core biopsies, there was an elevated risk of CaP.MethodsA retrospective analysis of the pathology database was conducted at our institution (Lancashire Teaching Hospitals NHS Foundation Trust) for prostate biopsies recorded between January 2001 and December 2005 (all extended core biopsies). Those patients with isolated HGPIN on 1st set of biopsies were identified and, their clinical characteristics and pathological findings from subsequent biopsies (if any) were determined. The risk of CaP on subsequent biopsies based on presenting baseline PSA was stratified.ResultsOf 2,192 biopsied patients, there were 88 cases of isolated HGPIN of which 67 patients underwent one or more repeat biopsies. In this repeat-biopsy group, 28 CaP diagnoses were made. Age at first biopsy (P < 0.001), higher mean baseline prostate-specific antigen (PSA) (P < 0.005) and higher mean change in PSA (P < 0.05) were predictive of CaP detection on repeat biopsies. PSA ranges and their associated predictive values for cancer were: 0 to 5 ng/ml – 11%; 5 to 10 ng/ml – 34%; 10 to 20 ng/ml – 50%; and > 20 ng/ml – 87.5%.ConclusionBased on our results, we recommend delaying the 1st repeat biopsy at low PSA range but to have a shorter interval to repeat biopsies at intermediate and higher PSA ranges.

Analysis of the Clinicopathologic Characteristics of Men with Prostate Cancer Undergoing Radical Prostatectomy in the Prostate-Specific Antigen Range of Less than 4 ng/ml

Purpose: We analyzed the clinicopathologic characteristics of men undergoing radical prostatectomy in the prostate-specific antigen (PSA) range of less than 4 ng/ml and compared this with the results for men who had a PSA range of 4 to 9.9 ng/ml. Materials and Methods: The study population consisted of 447 men treated for prostate cancer with radical prostatectomy between 1990 and 2006 at our institute who had a prebiopsy PSA of less than 10 ng/ml. The average follow-up period was 37 months. Clinicopathologic characteristics were compared between men with a PSA value of less than 4 ng/ml (low-PSA group) and men with a value in the range of 4 to 9.9 ng/ml (intermediatePSA group). Survival analysis was performed by the Kaplan-Meier method and Cox proportional hazard regression analysis. Results: Of these 447 patients, 60 (13.4%) and 387 (86.6%) had a low or an intermediate prebiopsy PSA level, respectively. The pathologic findings of the prostatectomy specimens showed no significant differences between the 2 groups, including Gleason score and pathologic stage. The 5-year biochemical recurrence-free survival in the lowand intermediate-PSA groups was 82.8% and 79.3%, respectively, and there was no significant difference between the 2 groups (p=0.946). Multivariate analysis showed that, in the entire cohort, pathologic Gleason score and lymph node involvement were independent predictors of biochemical recurrence. Conclusions: No statistically significant differences were found in clinicopathologic characteristics or clinical outcome between the lowand intermediate-PSA groups. These results suggest that a lower PSA cutoff should be considered as an indication for prostate biopsy in the Korean population. (Korean J Urol 2009;50:320-326) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

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.

Incidence of locally invasive prostate cancer in patients with intermediate values of prostate-specific antigen

Feasibility of radical prostatectomy (RP) in patients with locally invasive prostate cancer (PC) is assessed by the standard parameters such as the stage of the disease, serum prostate-specific antigen (PSA) and bioptic Gleason grade (GG). Intermediate values of PSA are important in predicting the local confines of the tumor, but can also be detected in more than 30% of patients with locally advanced PC. The aim of this study was to find out the incidence of locally advanced PC in the patients with intermediate serum PSA in whom RP had been performed. We used the biopsy cores and the tissue obtained after RP from 46 patients who had intermidiate PSA values which were defined as PSA from 2.6-10 ng/ml. In all the patients classical regional lymphadenectomy was performed. In all the patients, preoperative stage was determined according to the Partin tables (PT) from 2001. In 52, 17% of the patients biopsy GG was < or = 6, while it was 7 in 47.83% of the patients. Clinically localized disease (cT2b) was found in 86.96% of patients; other 13.04% of the patients had locally advanced PC. After RP, the incidence of localized PC was 47.83%, while the advanced disease was found in 52.17%. Metastasis in one or two regional lymph nodes (N1) was found in 10.87% of the patients with the advanced PC. According to PT, the expected incidence of positive lymph nodes should have been 8% for pT3 stage. Positive correlation between the assumed N1 stage according to PT and N1 stage in our radical prostatectomies was statistically significant (p = 0.012). In more than 50% of patients with intermediate values of PSA locally advanced disease can be expected after RP. The use of the Partin tables have an important predictive value in assessing the local confines of the cancer and metastasis in regional lymph nodes.

Prostate‐specific antigen adjusted for the transition zone volume as a second screening test: A prospective study of 248 cases

This study was conducted to verify the effectiveness of prostate-specific antigen adjusted for the transition zone volume (PSATZ), and its availability as a second screening test for prostate cancer detection. Total prostate-specific antigen (PSA) and free PSA was measured in male patients who visited our outpatient department for voiding difficulty or screening for prostate cancer. Patients who had an intermediate PSA level between 4.0 and 10.0 ng/mL, with an apparently normal prostate on a digital rectal examination, were enrolled. PSATZ, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative patients (benign) were conducted. Of 248 patients, 51 (20.6%) had prostate cancer and 197 (79.4%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSAD, F/T ratio and PSATZ were 7.48 +/- 1.77 ng/mL, 0.23 +/- 0.09 ng/mL per mL, 0.14 +/- 0.08 and 0.71 +/- 0.44 ng/mL per mL in patients with prostate cancer and 6.59 +/- 1.60 ng/mL, 0.16 +/- 0.07 ng/mL per mL, 0.21 +/- 0.11 and 0.36 +/- 0.30 ng/mL per mL in patients with benign, respectively. Receiver operating characteristics (ROC) curve analysis demonstrated that PSATZ predicted the biopsy outcome better than F/T ratio. With a cut-off value of 0.37 ng/mL per mL, PSATZ had a sensitivity of 74.5% and a specificity of 72.6% for predicting prostate cancer. The maximal cut-off value that preserves 100% of sensitivity was 0.2, and at this cut-off value, 16.1% of unnecessary biopsies could be reduced. Prostate-specific antigen adjusted for the transition zone volume may be more useful than other strategies in detecting prostate cancer in patients with intermediate PSA levels of 4.0-10.0 ng/mL. It can be used as a second screening test to reduce unnecessary biopsy.