Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

OBJECTIVE: To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). PATIENTS AND METHODS: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. RESULTS: In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively (P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. CONCLUSIONS: Addition of PSMA-PET to the conventional work-up by mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

Final Analysis of the Magnetic Resonance Imaging in Active Surveillance Trial.

PURPOSE: This study aimed to assess the medium-term oncologic outcomes of an active surveillance protocol, replacing confirmatory biopsy with serial multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 172 men were enrolled in this single-arm prospective trial. Men with prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with ≤10% Gleason pattern 4 overall and <2 cores Gleason pattern 4) eligible for surveillance were included in the study. Men underwent baseline multiparametric magnetic resonance imaging and template ± targeted biopsy, then multiparametric magnetic resonance imaging at years 1 and 2 with a 3-year end-of-protocol biopsy. Biopsies during the 3-year protocol period were triggered by abnormalities on multiparametric magnetic resonance imaging and/or increases in prostate specific antigen density (>0.2 ng/ml/cc). RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric magnetic resonance imaging to detect progression to clinically significant prostate cancer were 57% (95% CI 39%-74%), 82% (95% CI 74%-89%), 50% (95% CI 38%-62%), and 86% (95% CI 81%-90%), respectively. Both multiparametric magnetic resonance imaging and prostate specific antigen density were significant predictors for progression (multiparametric magnetic resonance imaging OR 6.20, 95% CI 2.72-14.16, P < .001; prostate specific antigen density OR 6.19, 95% CI 2.14-17.92, P = .001). Only 2.3% (4/172) of patients had false-negative multiparametric magnetic resonance imaging and high-risk pathological features (pT3 or high-volume International Society of Urological Pathology >2). After a median 69 months (Q1-Q3 56-79) follow-up of all patients in the cohort, freedom from biochemical recurrence, metastasis, and prostate cancer-related death were 99.3%, 100%, and 100%, respectively. CONCLUSIONS: Final analysis of the Magnetic Resonance Imaging in Active Surveillance trial indicates that there is minimal risk to omitting 1-year confirmatory biopsy during active surveillance if baseline magnetic resonance-targeted + saturation template biopsy was performed; however, standardized 3-year systematic biopsy should be performed due to occasional magnetic resonance imaging-invisible tumors.

Ureteric obstruction secondary to unusual metastasis of prostate cancer.

A case of ureteric metastasis secondary to prostate cancer. A 70-year-old man presented with a rising PSA five years post radical prostatectomy and salvage radiotherapy. Conventional staging (CT/bone scan) was negative but a 68Ga-PSMA-PET/CT scan and ureteroscopy later confirmed a ureteric metastasis. This was treated with robotic-assisted radical nephroureterectomy.

The Magnetic Resonance Imaging in Active Surveillance (MRIAS) Trial: Use of Baseline Multiparametric Magnetic Resonance Imaging and Saturation Biopsy to Reduce the Frequency of Surveillance Prostate Biopsies.

PURPOSE: Prospective studies are lacking in assessing the diagnostic utility of serial multiparametric magnetic resonance imaging to predict biopsy proven progression to clinically significant prostate cancer in men on active surveillance, as well as the oncologic safety of baseline magnetic resonance imaging and saturation diagnostic biopsy in replacing early confirmatory biopsy during active surveillance. MATERIALS AND METHODS: A total of 172 men were enrolled in this single arm prospective trial. Men with cT2 or lower histologically proven prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with 10% or less Gleason pattern 4 overall and less than 2 cores Gleason pattern 4) eligible for surveillance were included in the study. Men underwent baseline multiparametric magnetic resonance imaging and saturation biopsy followed by serial annual multiparametric magnetic resonance imaging until a 3-year end point per protocol saturation biopsy. The standardized 1-year confirmatory biopsy was omitted and biopsies during the protocol were triggered based on new abnormalities on multiparametric magnetic resonance imaging and prostate specific antigen density. RESULTS: We report the prespecified interim analysis of the first 100 men at 3 years. At baseline the median age was 64.5 (IQR 57.25-69) years, prostate specific antigen was 4.7 ng/ml (IQR 3.4-6.6), 91% had Gleason 3+3=6 prostate cancer and multiparametric magnetic resonance imaging was negative (Prostate Imaging Reporting and Data System 1/2/3) in 87% of men. Within 3 years 21% experienced pathological progression. The positive predictive value, negative predictive value, sensitivity and specificity for detection of clinically significant prostate cancer by surveillance multiparametric magnetic resonance imaging was 45%, 89%, 61% and 80%, respectively. Positive surveillance magnetic resonance imaging (p=0.002) and prostate specific antigen density greater than 0.2 ng/ml (p=0.042) had significant predictive value for clinically significant prostate cancer. CONCLUSIONS: Our novel active surveillance protocol incorporating multiparametric magnetic resonance imaging detected most cases of disease progression and may enable confirmatory biopsy to be deferred, but should not replace 3-year surveillance biopsy altogether due to occasional magnetic resonance imaging invisible tumors.

Diagnostic accuracy of 68 Ga-prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) and multiparametric (mp)MRI to detect intermediate-grade intra-prostatic prostate cancer using whole-mount pathology: impact of the addition of 68 Ga-PSMA PET to mpMRI.

OBJECTIVE: To evaluate the ability of prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET)/computed tomography (CT) to detect intermediate-grade intra-prostatic prostate cancer (PCa), and to determine if PSMA-PET improves the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: A total of 56 consecutive patients with International Society of Urological Pathology (ISUP) grade 2-3 PCa after radical prostatectomy, who underwent both mpMRI and PSMA-PET CT (hereafter PSMA-PET) preoperatively, were enrolled in this study. The accuracy of PSMA-PET, mpMRI alone, and the two procedures in combination was analysed for identifying ISUP grades 1-3 within a 12-segment model. The accuracy of a combined predictive model (PSMA-PET and mpMRI) was determined. Receiver-operating characteristic curve analysis to determine the optimal standardized uptake value (SUVmax ) for PSMA-PET in discriminating between ISUP grades 1 and ≥2 was performed. RESULTS: On a per-patient basis, the sensitivities for PSMA-PET and mpMRI in identifying ISUP grades 2-3 PCa were 100% and 97%, respectively. Assessing ISUP grade ≥2 PCa using a 12-segment analysis, PSMA-PET demonstrated greater diagnostic accuracy (area under the curve), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), with values of 0.91, 88%, 93%, 95% and 85%, respectively, than did mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3-5), at 0.79, 68%, 91%, 87%, and 75%, respectively. When used in combination (PSMA-PET and mpMRI PIRADS 4-5), sensitivity, specificity, NPV and PPV were 92%, 90%, 96% and 81%, respectively. The sensitivity for both techniques reduced markedly when assessing ISUP grade 1 PCa (18% for PSMA-PET, 10% for mpMRI). An SUVmax value of 3.95 resulted in 94% sensitivity and 100% specificity. CONCLUSION: PSMA-PET is accurate in detecting segments containing intermediate-grade intra-prostatic PCa (ISUP grade ≥ 2), compared with and complementary to mpMRI. By contrast the detection rate for ISUP grade 1 disease for both PSMA-PET and mpMRI was low.

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade.

Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on 68Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] ± bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial 68Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH ± bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUVmax, SUVmean, and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5-61) reduction in SUVmax was recorded by day 9 after AB. A reduction from baseline SUVmax occurred in 86.5% (6/7) men by day 9 (P < 0.04), with an associated PSA response in 100% men (P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27-97) (P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUVmax in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7-66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUVmax and SUVmean on PSMA PET compared with baseline (P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (-15% [IQR, 70-138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on 68Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.

68Ga-HBEDD PSMA-11 PET/CT staging prior to radical prostatectomy in prostate cancer patients: Diagnostic and predictive value for the biochemical response to surgery.

METHODS:: We analysed results of 142 males with staging PSMA prior to radical prostatectomy (RP). Data collected included PSMA PET/CT, bone scan (30/142), mpMRI (112/142), and pathological T stage (pT) stage, Gleason score, surgical margins and lymph node status at RP. Prostate-specific antigen (PSA) was documented at staging scan, and following surgery (median 45 days (interquartile range 38-59). A PSA of < 0.03 ng ml-1 was classified as surgical response (SR). Logistic regression was performed for association of pre-operative clinical variables and SR. RESULTS:: 97.9% (139/142) of males had positive intraprostatic findings on PSMA. 14.1 % (20/142) of males had further sites of extra prostatic disease identified on PSMA PET. In males with disease confined to the prostate, 82.9 % (92/111) achieved an SR, compared to 28.6 % (4/14) in males with extraprostatic disease identified (lymph node positive and distant metastatic disease) (p < 0.001). On binary logistic regression PSMA had a superior predictive value for SR than Gleason score, PSA (at time of imaging) or pT stage. MRI was less sensitive and more specific for SVI, and less sensitive for nodal involvement. CONCLUSION:: Extraprostatic disease identified on staging pre-operative PSMA PET is independently predictive of a poor surgical response to RP, and may indicate a need for a multimodality approach to treatment. ADVANCES IN KNOWLEDGE:: This is one of the first studies to correlate the PSMA PET's staging capacity to prostate cancer patient's outcomes to radical prostatectomy and indicates it's potential in predicting which patients will benefit from radical prostatectomy.

Leiomyoma in a Renal Allograft.

Leiomyomas are smooth muscle tumours that are rarely found in the kidney. There is one report of a leiomyoma in a kidney transplant in a paediatric recipient. Here, we report an adult renal transplant recipient who developed an Epstein-Barr virus-positive leiomyoma in his allograft 15 years after transplantation. The patient was converted to everolimus for posttransplant immunosuppression management and there was no sign of progression over a year.

Ureteric stricture secondary to unusual extension of prostatic adenocarcinoma.

This article describes an unusual finding in a patient who presented with an adenocarcinoma of the prostate and right hydronephrosis. A 68-year-old male presented with right hydronephrosis and a PSA of 96. DRE was consistent with cT3 carcinoma. Cystoscopy showed an exophytic superficial transitional cell carcinoma (TCC) of the bladder and a transrectal biopsy of the prostate confirmed adenocarcinoma Gleason score 4+3. Staging investigations (CT pelvis and bone scan) were negative; androgen deprivation therapy was therefore initiated for the prostatic adenocarcinoma. Upper tract imaging showed multiple filling defects in the proximal ureter. Ureteroscopy showed a stricture at the level of the iliac vessels. With a working diagnosis of upper tract TCC, right open nephroureterectomy was performed. Final histology showed prostatic adenocarcinoma infiltrating the adventitia of the entire ureter up to the level of the renal pelvis. A rare cause of ureteric stricture, contiguous spread of prostatic adenocarcinoma, should be considered in the differential diagnosis of patients presenting with upper tract obstruction and a known history of prostatic adenocarcinoma. Androgen deprivation therapy for several months did not seem to cause resolution of the tumor in the periureteric, ureteric and perihilar tissues.

Aberrant neuropeptide Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis.

Studies to elucidate dysregulated gene expression patterns in premalignant prostate lesions have identified several candidate genes with the potential to be targeted to prevent the development and progression of prostate cancer and act as biomarkers of early disease. Herein, we explored the importance of two proteins, neuropeptide Y (NPY) and macrophage inhibitory cytokine-1 (MIC-1), as biomarkers of preinvasive prostate disease and investigated the relationship of expression to biochemical recurrence following treatment for localized prostate cancer. NPY and MIC-1 protein expression was determined by immunohistochemistry on tissue microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial neoplasia (PIN), high-grade PIN (HGPIN), and prostate cancer tissue from 243 radical prostatectomy patients. Both NPY and MIC-1 showed higher proportional immunostaining in HGPIN and prostate cancer compared with benign epithelium (P < 0.0001). NPY and MIC-1 immunostaining was higher in low-grade PIN compared with other benign tissues (both P < 0.0001) and was equivalent to immunostaining in HGPIN. NPY immunostaining of prostate cancer was independently associated with relapse, after adjusting for traditional prognostic factors, as a categorical variable in 20% intervals (P = 0.0449-0.0103) and as a continuous variable (P = 0.0017). Low MIC-1 immunostaining (20% categories) was associated with pathologic stage >2C after adjusting for predictors of pathologic stage (P = 0.3894-0.0176). This is the first study to show that altered NPY and MIC-1 expression are significantly associated with prostate cancer progression and suggests that these molecules be developed further as biomarkers in the management of prostate disease.

Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized prostate cancer.

Beta-catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of beta-catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for beta-catenin expression using immunohistochemistry. Nuclear beta-catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear beta-catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse-free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate-specific antigen (PSA) levels (p = 0.01). Analysis of the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear beta-catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear beta-catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear beta-catenin expression may be of clinical utility as a preoperative prognostic marker in low-risk localized PC.

Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression.

BACKGROUND: The role of the bone morphogenetic protein (BMP) pathway in prostate cancer (PC) is unclear. This study aimed to characterize aspects of the BMP pathway in PC by assessing BMP2, Smad8, and Smad4 expression in normal, hyperplastic, and malignant prostate tissue, and to correlate findings with progression to PC. METHODS: Radical prostatectomy (RP) specimens from 74 patients with clinically localized PC (median follow-up 51 months, range 15-152), 44 benign prostatic hypertrophy (BPH) lesions, and 4 normal prostates (NPs) were assessed for BMP2, Smad8, and Smad4 expression using immunohistochemistry. RESULTS: Both BMP2 (P < 0.001) and nuclear Smad4 (P < 0.0001) expression were significantly decreased in PC compared to benign prostate tissue. Nuclear Smad8 was present in normal/benign prostate tissue but absent in PC and adjacent hyperplasia. Furthermore, loss of BMP2 (P < 0.001) and decreased nuclear Smad4 (P = 0.05) expression correlated with increasing Gleason score. CONCLUSIONS: These data suggest that decreased BMP2, nuclear smad8 and nuclear Smad4 expression are associated with the progression to PC, and in particular loss of BMP2 and Smad4 are related to progression to a more aggressive phenotype.

Membranous expression of secreted frizzled-related protein 4 predicts for good prognosis in localized prostate cancer and inhibits PC3 cellular proliferation in vitro.

PURPOSE: Activation of the Wnt-signaling pathway is implicated in aberrant cellular proliferation in a variety of cancers. Secreted frizzled-related protein 4 (sFRP4) is a secreted protein with putative inhibitory activity of the Wnt-signaling cascade through binding and sequestering Wnt ligands. Because sFRP4 mRNA is overexpressed in prostate cancers (PCs), the aim of this study was to define the pattern of sFRP4 protein expression in normal and malignant human prostate tissue and to determine whether changes in expression were associated with disease progression and prognosis, as well as to define the phenotype of sFRP4-overexpression in an in vitro model of PC. EXPERIMENTAL DESIGN: Polyclonal antibodies were raised against a COOH-terminal peptide of sFRP4, characterized and used to assess sFRP4 protein expression in benign prostate tissue and 229 patients with clinically localized PC (median follow-up 77 months, range 1-156). In vitro studies of the function of sFRP4 overexpression were performed using PC3 cells transfected with sFRP4. RESULTS: Benign and malignant prostate tissue demonstrated cytoplasmic sFRP4 immunoreactivity, but there was a decrease in the expression of membranous sFRP4 in PCs compared with the hyperplastic lesions (P < 0.0001). Kaplan-Meier analysis revealed that patients whose PC expressed membranous sFRP4 in >20% of cells had improved relapse-free survival compared with those with

Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma.

BACKGROUND: In the current study, the authors sought to further stratify the prognosis of patients with Gleason score (GS) 7 prostate carcinoma. They assessed the influence on outcome of a predominant poorly differentiated Gleason pattern (primary Gleason pattern [GP] 4) and/or a coincident small focus of poorly differentiated tumor of higher grade (tertiary GP 5). METHODS: The authors studied 412 patients (mean postoperative follow-up, 33 months) with GS 7 tumors treated with radical prostatectomy at a single Australian campus between November 1989 and December 2002. The chi-square test, Kaplan-Meier method, and Cox proportional hazards analyses were used to evaluate the correlation between primary GP 4 and tertiary GP 5 with the occurrence of adverse pathologic features and disease recurrence. RESULTS: In this cohort, 307 patients (75%) had primary GP 3 tumors, 105 (25%) had primary GP 4 tumors, and 17 (2.3%) had a tertiary element of high-grade tumor (GP 5). Patients with primary GP 4 tumors displayed higher rates of seminal vesicle involvement and extraprostatic extension and, along with patients with tertiary GP 5, had significantly shorter times to disease recurrence. Univariate analysis demonstrated that primary GP 4 (P = 0.0003) and tertiary GP 5 (P < 0.0001) were strong predictors of disease recurrence. Primary GP 4 (P = 0.0122) remained an independent predictor of disease recurrence on stepwise multivariate analysis. CONCLUSIONS: Primary GP 4 tumors represented an aggressive subset of GS 7 prostate carcinomas. Primary GP was an easily accessible and clinically relevant predictor of disease recurrence in patients with GS 7 prostate carcinoma.

Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer.

We have utilized oligonucleotide microarrays to identify novel genes of potential clinical and biological importance in prostate cancer. RNA from 74 prostate cancers and 164 normal body samples representing 40 different tissues were analysed using a customized Affymetrix GeneChip oligonucleotide microarray representative of over 90% of the expressed human genome. The gene for the zinc transporter ZnT4 was one of several genes that displayed significantly higher expression in prostate cancer compared to normal tissues from other organs. A polyclonal antipeptide antibody was used to demonstrate ZnT4 expression in the epithelium of all 165 elements of benign and 326 elements of localized prostate cancers examined and in nine of 10 advanced prostate cancer specimens by immunohistochemistry. Interestingly, decreased intensity of ZnT4 immunoreactivity occurred in the progression from benign to invasive localized prostate cancer and to metastatic disease. Immunofluorescence analysis and surface biotinylation studies of cells expressing ZnT4 localised the protein to intracellular vesicles and to the plasma membrane. These findings are consistent with a role for ZnT4 in vesicular transport of zinc to the cell membrane and potentially in efflux of zinc in the prostate.

Prognostic significance of preoperative factors in localized prostate carcinoma treated with radical prostatectomy: importance of percentage of biopsies that contain tumor and the presence of biopsy perineural invasion.

BACKGROUND: Predicting outcome for men with clinically localized prostate carcinoma treated with curative intent remains imprecise and further evaluation of accepted and potential predictive factors is needed. METHODS: The authors studied 696 men with localized prostate carcinoma diagnosed on transrectal biopsy and treated with radical prostatectomy at one institution between 1986 and 1999 to determine the relation between putative pretreatment prognostic factors and disease-free survival. Clinical stage, Gleason score, perineural invasion, number of biopsies containing tumor, and serum prostate specific antigen (PSA) were evaluated as predictors of extracapsular extension, seminal vesicle involvement, lymph node metastases, and surgical margin involvement as well as outcome after surgery. Kaplan-Meier method and Cox regression analyses were used to evaluate the contribution of different factors to adverse pathologic features and relapse. RESULTS: At mean follow-up of 56.9 months (range, 1.0-177.9 months; median, 54.9 months), 26.1% (182 of 696 patients) of patients had developed a disease recurrence. Pretreatment serum PSA concentration, biopsy Gleason score, and clinical stage as well as number of biopsies involved with tumor as a percentage of the total number obtained were found to be independent predictors of outcome. In patients with PSA > 10 ng/mL, biopsy perineural invasion and percentage of biopsies containing tumor were found to independently predicted disease recurrent. Increased number of biopsies involved with tumor independently predicted extracapsular extension, margin involvement, seminal vesicle, and lymph node involvement. CONCLUSIONS: This study demonstrated that the proportion of prostate biopsy cores containing tumor is an independent predictor of outcome after subsequent radical prostatectomy and suggested that perineural invasion has a predictive role in patients with a preoperative PSA > 10 ng/ml.