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.

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.

Radiomic features on MRI enable risk categorization of prostate cancer patients on active surveillance: Preliminary findings.

BACKGROUND: Radiomic analysis is defined as computationally extracting features from radiographic images for quantitatively characterizing disease patterns. There has been recent interest in examining the use of MRI for identifying prostate cancer (PCa) aggressiveness in patients on active surveillance (AS). PURPOSE: To evaluate the performance of MRI-based radiomic features in identifying the presence or absence of clinically significant PCa in AS patients. STUDY TYPE: Retrospective. SUBJECTS MODEL: MRI/TRUS (transperineal grid ultrasound) fusion-guided biopsy was performed for 56 PCa patients on AS who had undergone prebiopsy. FIELD STRENGTH/SEQUENCE: 3T, T2 -weighted (T2 w) and diffusion-weighted (DW) MRI. ASSESSMENT: A pathologist histopathologically defined the presence of clinically significant disease. A radiologist manually delineated lesions on T2 w-MRs. Then three radiologists assessed MRIs using PIRADS v2.0 guidelines. Tumors were categorized into four groups: MRI-negative-biopsy-negative (Group 1, N = 15), MRI-positive-biopsy-positive (Group 2, N = 16), MRI-negative-biopsy-positive (Group 3, N = 10), and MRI-positive-biopsy-negative (Group 4, N = 15). In all, 308 radiomic features (First-order statistics, Gabor, Laws Energy, and Haralick) were extracted from within the annotated lesions on T2 w images and apparent diffusion coefficient (ADC) maps. The top 10 features associated with clinically significant tumors were identified using minimum-redundancy-maximum-relevance and used to construct three machine-learning models that were independently evaluated for their ability to identify the presence and absence of clinically significant disease. STATISTICAL TESTS: Wilcoxon rank-sum tests with P < 0.05 considered statistically significant. RESULTS: Seven T2 w-based (First-order Statistics, Haralick, Laws, and Gabor) and three ADC-based radiomic features (Laws, Gradient and Sobel) exhibited statistically significant differences (P < 0.001) between malignant and normal regions in the training groups. The three constructed models yielded overall accuracy improvement of 33, 60, 80% and 30, 40, 60% for patients in testing groups, when compared to PIRADS v2.0 alone. DATA CONCLUSION: Radiomic features could help in identifying the presence and absence of clinically significant disease in AS patients when PIRADS v2.0 assessment on MRI contradicted pathology findings of MRI-TRUS prostate biopsies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Radiomic features for prostate cancer detection on MRI differ between the transition and peripheral zones: Preliminary findings from a multi-institutional study.

PURPOSE: To evaluate in a multi-institutional study whether radiomic features useful for prostate cancer (PCa) detection from 3 Tesla (T) multi-parametric MRI (mpMRI) in the transition zone (TZ) differ from those in the peripheral zone (PZ). MATERIALS AND METHODS: 3T mpMRI, including T2-weighted (T2w), apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced MRI (DCE-MRI), were retrospectively obtained from 80 patients at three institutions. This study was approved by the institutional review board of each participating institution. First-order statistical, co-occurrence, and wavelet features were extracted from T2w MRI and ADC maps, and contrast kinetic features were extracted from DCE-MRI. Feature selection was performed to identify 10 features for PCa detection in the TZ and PZ, respectively. Two logistic regression classifiers used these features to detect PCa and were evaluated by area under the receiver-operating characteristic curve (AUC). Classifier performance was compared with a zone-ignorant classifier. RESULTS: Radiomic features that were identified as useful for PCa detection differed between TZ and PZ. When classification was performed on a per-voxel basis, a PZ-specific classifier detected PZ tumors on an independent test set with significantly higher accuracy (AUC = 0.61-0.71) than a zone-ignorant classifier trained to detect cancer throughout the entire prostate (P < 0.05). When classifiers were evaluated on MRI data from multiple institutions, statistically similar AUC values (P > 0.14) were obtained for all institutions. CONCLUSION: A zone-aware classifier significantly improves the accuracy of cancer detection in the PZ. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:184-193.

Repeat transurethral resection for non-muscle-invasive bladder cancer: a contemporary series.

OBJECTIVES: To evaluate the depth of transurethral resections of bladder tumour (TURBT), residual cancer rates and up-staging rates in a contemporary Australian series. MATERIALS AND METHODS: Specimen reports from a single, major reporting pathology centre, servicing a group of urological oncologists in Sydney were obtained for TURBTs performed between October 2008 and February 2013. We examined the depth of TURBT, rates of repeat-TURBT (re-TUR) and residual cancer rates at the 3-6 month check cystoscopy. RESULTS: One thousand and two hundred and nine transurethral resection specimens retrieved during this period were analysed. There were 162 (13.4%) T1 specimens and 631 (52.2%) Ta specimens, 218 (34.5%) of which were high grade. Muscularis propria was present in 506 (41.9%) specimens in total and in 151 (39.7%) of 380 high-risk specimens (high grade Ta, T1). Of the 380 high-risk non-muscle-invasive tumours, 85 (22.4%) proceeded to re-TUR. Of the 48 T1 specimens and 37 Ta high grade specimens that proceeded to re-TUR, 7 (14.6%) and 1 (2.7%) respectively were upstaged to muscle-invasive disease. Rates of residual disease/early recurrence at 3-6 months was significantly better for those with re-TUR compared to those without 56.8% vs 82.5% (P < 0.001) for Ta high grade and 39.6% vs 84% (P = 0.028) for T1 tumours respectively. CONCLUSION: Re-TUR rates in high-risk non-muscle-invasive bladder cancer are low. However in a contemporary series, the upstaging rates are low, but residual cancer rates high, supporting the need for re-TUR in this population.

Combination of multiparametric MRI and transperineal template-guided mapping biopsy of the prostate to identify candidates for hemi-ablative focal therapy.

OBJECTIVE: To evaluate the accuracy of combined multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) for identifying lobes with significant prostate cancer (PCa) for the application of hemi-ablative focal therapy (FT). PATIENTS AND METHODS: From January 2012 to January 2014, 89 consecutive patients, aged ≥40 years, with a PSA level ≤15 ng/mL, underwent in sequential order: mpMRI, TTMB and radical prostatectomy (RP) at a single centre. Analysis was performed on 50 patients who met consensus guidelines for FT. Lobes were stratified into lobes with significant cancer (LSC), lobes with insignificant cancer and lobes with no cancer. Using histopathology at RP, the predictive performance of combined mpMRI + TTMB in identifying LSC was evaluated. RESULTS: The sensitivity, specificity and positive predictive value for mpMRI + TTMB for LSC were 97, 61 and 83%, respectively. The negative predictive value (NPV), the primary variable of interest, for mpMRI + TTMB for LSC was 91%. Of the 50 patients, 21 had significant unilateral disease on mpMRI + TTMB. Two of these 21 patients had significant bilateral disease on RP not identified on mpMRI + TTMB. CONCLUSIONS: In the selection of candidates for FT, a combination of mpMRI and TTMB provides a high NPV in the detection of LSC.

Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over-treatment.

BACKGROUND: There are conflicting results in the literature regarding the tumor volume (TV) threshold that defines insignificant prostate cancer (PCa). In this study, we retrospectively evaluate the association of an increasing TV with biochemical recurrence (BCR) following radical prostatectomy (RP) in order to provide further clarification surrounding the TV threshold definition for insignificant PCa. METHODS: RP patients were recruited from January 2004 to December 2009. Inclusion criteria were localized (stage ≤pT2c, negative surgical margins) Gleason 6 PCa with a total TV of ≤2.50 cm(3) . BCR was the primary outcome and defined as a PSA of ≥0.1. All cases with BCR were re-evaluated by the pathologist with reassessment of tumor grade, pathological stage and surgical margin status. RESULTS: From 1,636 patients, 178 men (10.9%) met all inclusion criteria. Ninety-six patients (53.9%) had a TV <0.5 cm(3) and 82 patients (46.1%) had a TV 0.5-2.5 cm(3) . Three out of 178 patients (1.7%) presented with BCR during follow-up. One of these had TV <0.5 cm(3) and two had TV 0.5-2.5 cm(3) . These three cases of BCR underwent re-review of pathology; one patient was found to have a positive surgical margin and one patient was upgraded to Gleason 3 + 4 = 7. The third patient was re-reported as having positive margins for a benign hyperplastic nodule (incomplete RP specimen). Subsequently, these three cases were excluded from final analysis as they did not fit inclusion criteria. Median follow-up duration was 84 months (IQR 70-102 months). On final analysis, there were no patients with BCR, corresponding with a final BCR rate of 0% for both patients with a TV of <0.5 cm(3) and 0.5-2.5 cm(3) . CONCLUSIONS: Our results have shown that, with a median follow-up of 84 (IQR 70-102) months, patients in our cohort with localized Gleason 6 PCa with a total TV 0.5-2.5 cm(3) have a BCR rate of 0%. We would support a more liberal total TV threshold of 2.5 cm(3) for the further development of algorithms to identify patients suitable for active surveillance.

Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: a prospective study.

PURPOSE: Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospective studies are lacking. We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination. MATERIALS AND METHODS: In this single center, prospective study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil. Imaging was allocated alternately to 1.5/3.0 Tesla. Imaging was double reported independently using PI-RADS (Prostate Imaging Reporting and Data System) by specialist radiologists. Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations. Four significant cancer definitions were tested. Chi-square and logistic regression analysis was done. Men undergoing prostatectomy were analyzed. RESULTS: Of the 165 men who enrolled in the study 150 were analyzed. Median age was 62.4 years, median prostate specific antigen was 5.6 ng/ml, 29% of patients had an abnormal digital rectal examination and 88% underwent initial biopsy. Multiparametric magnetic resonance imaging was positive (PI-RADS 3 to 5) in 66% of patients, 61% had prostate cancer and 30% to 41% had significant prostate cancer (definitions 1 to 4). For significant cancer sensitivity was 93% to 96%, specificity was 47% to 53%, and negative and positive predictive values were 92% to 96% and 43% to 57%, respectively (definitions 1 to 4). Radical prostatectomy results in 48 men were similar. Aggregate PI-RADS (4 to 20) performed similarly to overall PI-RADS (1 to 5). Negative and positive predictive values (100% and 71%, respectively) were similar in men at higher risk, defined as prostate specific antigen greater than 10 ng/ml with abnormal digital rectal examination. On multivariate analysis PI-RADS score was associated with significant prostate cancer (p <0.001) but magnet strength was not. Adding PI-RADS to the multivariate model improved the AUC from 0.810 to 0.913 (95% CI 0.038-0.166, p = 0.002). Radiologist agreement was substantial (weighted κ = 0.626). CONCLUSIONS: Multiparametric magnetic resonance imaging reported by expert radiologists achieved an excellent negative predictive value and a moderate positive predictive value for significant prostate cancer at 1.5 and 3.0 Tesla.

Outcomes of transperineal template-guided prostate biopsy in 409 patients.

OBJECTIVE: To present the template-guided transperineal prostate biopsy (TPB) outcomes for patients of two urologists from a single institution. PATIENTS AND METHODS: We conducted a prospective study of 409 consecutive men who underwent TPB between December 2006 and June 2008 in a tertiary referral centre using a standardized 14-region technique. The procedure was performed as day surgery under general anaesthesia with fluoroquinolone antibiotic cover. Follow-up took place within 2 weeks, during which time men were interviewed using a standardized template. Results were compared with those of the Australian national prostate biopsy audits performed by the Urological Society of Australia and New Zealand (USANZ). RESULTS: Indications for biopsy included elevated prostate-specific antigen (PSA) level (75%), with a median PSA level of 6.5 ng/mL, abnormal digital rectal examination (8%) and active surveillance (AS) re-staging (18%). The mean patient age was 63 years and two-thirds of patients were undergoing their first biopsy. A positive biopsy was found in 232 men, 74% of whom had a Gleason score of ≥7. The overall cancer detection rate was 56.7% (USANZ 2005 national audit = 56.5%). Stratified between those having their first TPB or a repeat procedure (after a previous negative biopsy), the detection rates were 64.4 and 35.6%, respectively. Significantly higher detection rates were found in prostates <50 mL in volume than in larger prostates (65.2 vs 38.3%, respectively, P < 0.001). Haematuria was the most common side effect (51.7%). Others included dysuria (16.4%), acute urinary retention (4.2%) and fever (3.2%). One patient (0.2%) had septicaemia requiring i.v. antibiotics. Repeat biopsy was not associated with increased complication rates. CONCLUSIONS: TPB is a safe and efficacious technique, with a cancer detection rate of 56.7% in the present series, and a low incidence of major side effects. Stratified by prostate volume, the detection rate of TPB was higher in smaller glands. Given the relatively low rate of serious complications, clinicians could consider increasing the number of TPB biopsy cores in larger prostates as a strategy to improve cancer detection within this group. Conversely, in patients on AS programmes, a staging TPB may be a superior approach for patients undergoing repeat biopsy so as to minimize their risk of serious infection.

Accuracy of primary systematic template guided transperineal biopsy of the prostate for locating prostate cancer: a comparison with radical prostatectomy specimens.

PURPOSE: We determined whether systematic template guided transperineal biopsies can accurately locate and sensitively detect prostate cancer. In addition, we reported discrepancies between diagnostic and pathological Gleason scores, and investigated whether prostate size had an effect on the cancer detection rate. MATERIALS AND METHODS: This retrospective diagnostic accuracy study compares the results of primary transperineal biopsies with the radical prostatectomy pathology of 414 consecutive patients treated at a single institution between November 2002 and August 2010. RESULTS: The average sensitivity and specificity for the detection of cancer in all prostates across all biopsy zones was 48% (95% CI 42.6-53.4) and 84.1% (95% CI 80-88.2), respectively. There was a statistically significant decrease in the sensitivity of transperineal biopsy in larger prostates (t11=4.687, p=0.001). The overall Kappa value was 0.255 (95% CI 0.212-0.298). Grading concordance between biopsy and pathology specimens was achieved in 65.7% of patients. Upgrading of Gleason scores occurred in 25.6% of patients and downgrading occurred in 8.8%. CONCLUSIONS: Our current transperineal biopsy method has only demonstrated fair agreement with the histopathology findings of the corresponding radical prostatectomy specimens. This finding is most likely due to the small, multifocal nature of prostate cancer in the patient series. The cancer detection rate was lower in larger prostates. Thus, clinicians may consider increasing the number of cores in larger prostates as a strategy to improve cancer detection.

Location and pathological characteristics of cancers in radical prostatectomy specimens identified by transperineal biopsy compared to transrectal biopsy.

PURPOSE: Anterior tumors are estimated to constitute 20% of prostate cancers. Current data indicate that transperineal biopsy is more reliable than transrectal biopsy in identifying these tumors. If correct, this superior reliability should result in an increased proportion of anterior tumors identified by transperineal biopsy. We investigated this hypothesis with reference to prostatectomy specimens. MATERIALS AND METHODS: Radical prostatectomy histopathology records were retrospectively examined. Patients were grouped based on primary transperineal or transrectal biopsy as the modality used to identify the initial cancer. After grouping, tumor location and size were recorded and, thus, the proportion of anterior tumors was determined. RESULTS: A total of 1,132 (414 transperineal and 718 transrectal) prostatectomy specimens were examined. Overall mean tumor size (1.8 and 2.0 cm(3)), stage (pT2 63.3% and 61%) and significance (5.1% and 5.1%) for the transperineal and transrectal methods were similar. However, the transperineal method was associated with proportionally more anterior tumors (16.2% vs 12%, p = 0.046), and identified them at a smaller size (1.4 vs 2.1 cm(3), p = 0.03) and lower stage (extracapsular extension 13% vs 28%, p = 0.03) compared to the transrectal method. The pT3 positive surgical margin rate for anterior vs other tumors was 69% vs 34.9%, respectively. CONCLUSIONS: Overall transrectal and transperineal biopsy identify cancers that are similar in size, stage and significance. However, transperineal biopsy detected proportionally more anterior tumors (16.2% vs 12%), and identified them at a smaller size (1.4 vs 2.1 cm(3)) and stage (extracapsular extension 13% vs 28%) compared to transrectal biopsy. Identifying anterior tumors early is important because the positive surgical margin rate for anterior pT3 lesions is significantly higher.

High-dose rate brachytherapy compared with open radical prostatectomy for the treatment of high-risk prostate cancer: 10 year biochemical freedom from relapse.

OBJECTIVE: • To compare long-term biochemical control of high-risk prostate cancer in those men receiving high-dose rate brachytherapy (HDRB) and radical prostatectomy (RP). PATIENTS AND METHODS: • The 10-year biochemical freedom from relapse (BFR) was calculated for 243 patients who underwent either RP or combined therapy with HDRB + external beam radiotherapy + androgen deprivation between 1998 and 2000. • INCLUSION CRITERIA: clinical stage ≥ T2b, or Gleason sum ≥ 8, or PSA level of > 20 ng/mL. Groups were appraised using the Kattan nomogram for surgery to calculate progression-free probability (PFP). RESULTS: • For the RP group (153 patients) the median PSA level was 8.1 ng/mL and the median age was 62.2 years. The median 5- and 10-year predicted PFP for RP was 64% and 56 %, respectively. The 5- and 10-year BFR was 65.5% and 55.4%. There was no significant difference between the predicted and the actual PFP for the RP group (P= 0.525). • For HDRB group (90 patients). The median PSA level was 14.2 ng/mL and the median age was 67.6 years. The median 5- and 10-year predicted PFP for HDRB was 46% and 35%, respectively. The 5- and 10-year BFR was 79.6% and 53.6%. There was a significant improvement between the actual and the predicted PFP for the HDRB group (P= 0.002). CONCLUSIONS: • Amongst a high-risk cohort, patients undergoing RP performed as predicted by the pre-treatment surgical nomogram, whereas the patients undergoing HDRB performed significantly better than was predicted by the surgical nomogram at 10 years.

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.

Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies.

Introduction. To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods. Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA <10 ng/mL, Gleason score <8 PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1-5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume <2.5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume <0.7 mL). Results. 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC. Conclusions. Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies.

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.

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

Early Experience in Da Vinci Robot-Assisted Partial Nephrectomy: An Australian Single Centre Series.

Introduction and Objectives. To demonstrate the safety and efficacy of the robot-assisted partial nephrectomy (RAPN) technique in an Australian setting. Methods. Between November 2010 and July 2014, a total of 76 patients underwent 77 RAPN procedures using the Da Vinci Surgical System© at our institution. 58 of these procedures were performed primarily by the senior author (PB) and are described in this case series. Results. Median operative time was 4 hours (range 1.5-6) and median warm ischaemic time (WIT) was 8 minutes (range 0-30) including 11 cases with zero ischaemic time. All surgical margins were clear with the exception of one patient who had egress of intravascular microscopic tumour outside the capsule to the point of the resection margin. Complications were identified in 9 patients (15.8%). Major complications included conversion to open surgery due to significant venous bleeding (n = 1), reperfusion injury (n = 1), gluteal compartment syndrome (n = 1), DVT/PE (n = 1), and readmission for haematuria (n = 1). Conclusion. This series demonstrates the safety and efficacy of the RAPN technique in an Australian setting when performed by experienced laparoscopic surgeons in a dedicated high volume robotic centre.

Pathological evaluation and quality of surgery in radical cystectomy in New South Wales, Australia.

BACKGROUND: Australian bladder cancer patients especially women are thought to have worse outcomes when compared to the other international series. The objective of this study was to assess the pathological pattern of primary bladder cancer at the time of radical cystectomy as well as assessing the quality of resection in New South Wales. METHOD: Pathology reports of radical cystectomy performed for primary bladder cancer were reviewed for a period of 10 years in a single major pathology centre servicing the state of New South Wales. RESULTS: Two hundred one specimens reviewed over 10 years. The tumour stage at the time of cystectomy was: CIS 29 (14%), Tx,a 5 (2%), T1 24 (12%), T2 49 (24%), T3 57 (28%) and T4 37 (18%). Lymphovascular invasion was seen in 94 (47%). Soft tissue margins were positive in 31 (15%), pelvic lymph node dissection was not performed in 64 (32%) of patients and only 32 (16%) of the patients had 10 or more lymph nodes harvested. No significant differences between men and women were noted in tumour stages, soft tissue positive margin rates and performance of pelvic lymph node dissection. Improving trends were noted in rates of negative soft tissue margins and the lymph node count during this period. CONCLUSION: Pattern of disease at the time of cystectomy was similar to the North American and European cohorts. Higher main specimen margin rates as well as lower lymph nodes retrieval rates were observed. No sex discrimination was observed. Further study is recommended to investigate the survival impact of this finding.

Cancer identified incidentally in the prostate following radical cystoprostatectomy: an Australian study.

BACKGROUND: The aim of this study was to determine the incidence and tumour characteristics of incidental prostatic cancer in Australian men with primary bladder cancer undergoing radical cystoprostatectomy (RCP). METHOD: Cystoprostatectomy specimens were reviewed for a 10-year period from a leading pathology centre in the state of New South Wales, Australia. Stamey classification was used to define significant prostate cancer. RESULTS: One hundred twenty-nine patients underwent RCP, 50 (39%) had prostatic adenocarcinoma, of which 35 (70%) were clinically significant. Apical involvement was seen in 10 (20%) of which 8 (16%) were clinically significant. High-grade intraepithelial neoplasia was seen in 27 (21%) and urothelial carcinoma or extension of bladder tumour was seen in 15 (12%) and 10 (8%) respectively. Bladder carcinoma in situ (CIS) was strongly associated with presence of urethral disease (P = 0.008). CONCLUSION: High rates of prostatic involvement with adenocarcinoma and as well as urothelial malignancy was detected in patients with primary bladder cancer undergoing cystoprostatectomy. Large proportions of prostate adenocarcinoma were clinically significant. Presence of bladder CIS was significantly associated with presence of prostatic urethral disease.