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OBJECTIVE: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa). METHODS: The European Association of Urology-European Association of Nuclear Medicine-European Society for Radiotherapy and Oncology-European Society of Urogential Radiology-International Society of Urological Pathology-International Society of Geriatric Oncology and American Urological Association-American Society for Radiation Oncology-Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed. RESULTS: Our results showed a lack of long-term randomised data for FT. International Urological guidelines emphasised the need for more high-quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous. CONCLUSION: A globally accepted guideline for FT planning, technique and follow-up are still yet to be determined. Well-designed studies with long-term follow-up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow-up.

Objective: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. Patients and Methods: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. Result(s): The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of >= grade 3 adverse events. Conclusion(s): We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.Copyright © 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU Intern

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naive primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.Copyright © 2021, The Author(s).

Purpose: Estimation of accurate attenuation maps for whole-body positron emission tomography (PET) imaging in simultaneous PET-MRI systems is a challenging problem as it affects the quantitative nature of the modality. In this study, we aimed to improve the accuracy of estimated attenuation maps from MRI Dixon contrast images by training an augmented generative adversarial network (GANs) in a supervised manner. We augmented the GANs by perturbing the non-linear deformation field during image registration between MRI and the ground truth CT images. Method(s): We acquired the CT and the corresponding PET-MR images for a cohort of 28 prostate cancer patients. Data from 18 patients (2160 slices and later augmented to 270,000 slices) was used for training the GANs and others for validation. We calculated the error in bone and soft tissue regions for the AC mu-maps and the reconstructed PET images. Result(s): For quantitative analysis, we use the average relative absolute errors and validate the proposed technique on 10 patients. The DL-based MR methods generated the pseudo-CT AC mu-maps with an accuracy of 4.5% more than standard MR-based techniques. Particularly, the proposed method demonstrates improved accuracy in the pelvic regions without affecting the uptake values. The lowest error of the AC mu-map in the pelvic region was 1.9% for mu-mapGAN + aug compared with 6.4% for mu-mapdixon, 5.9% for mu-mapdixon + bone, 2.1% for mu-mapU-Net and 2.0% for mu-mapU-Net + aug. For the reconstructed PET images, the lowest error was 2.2% for PETGAN + aug compared with 10.3% for PETdixon, 8.7% for PETdixon + bone, 2.6% for PETU-Net and 2.4% for PETU-Net + aug.. Conclusion(s): The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated mu-map and consequently the PET quantification compared to the state of the art.Copyright © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Objective: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. Patients and Methods: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. Result(s): The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of >= grade 3 adverse events. Conclusion(s): We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.Copyright © 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU Intern

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naive primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.Copyright © 2021, The Author(s).

Purpose: Estimation of accurate attenuation maps for whole-body positron emission tomography (PET) imaging in simultaneous PET-MRI systems is a challenging problem as it affects the quantitative nature of the modality. In this study, we aimed to improve the accuracy of estimated attenuation maps from MRI Dixon contrast images by training an augmented generative adversarial network (GANs) in a supervised manner. We augmented the GANs by perturbing the non-linear deformation field during image registration between MRI and the ground truth CT images. Method(s): We acquired the CT and the corresponding PET-MR images for a cohort of 28 prostate cancer patients. Data from 18 patients (2160 slices and later augmented to 270,000 slices) was used for training the GANs and others for validation. We calculated the error in bone and soft tissue regions for the AC mu-maps and the reconstructed PET images. Result(s): For quantitative analysis, we use the average relative absolute errors and validate the proposed technique on 10 patients. The DL-based MR methods generated the pseudo-CT AC mu-maps with an accuracy of 4.5% more than standard MR-based techniques. Particularly, the proposed method demonstrates improved accuracy in the pelvic regions without affecting the uptake values. The lowest error of the AC mu-map in the pelvic region was 1.9% for mu-mapGAN + aug compared with 6.4% for mu-mapdixon, 5.9% for mu-mapdixon + bone, 2.1% for mu-mapU-Net and 2.0% for mu-mapU-Net + aug. For the reconstructed PET images, the lowest error was 2.2% for PETGAN + aug compared with 10.3% for PETdixon, 8.7% for PETdixon + bone, 2.6% for PETU-Net and 2.4% for PETU-Net + aug.. Conclusion(s): The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated mu-map and consequently the PET quantification compared to the state of the art.Copyright © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Abstract Purpose To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FF

BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1-31.3] and 24.2 (IQR 17.9-30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12-24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12-18 months post-treatment. We have commence

New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.

PURPOSE: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2, a key regulator of EMT reprogramming. CONCLUSION: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2, a key transcriptional regulator of EMT, correlates with clinical response.

PURPOSE: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). METHODS: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). RESULTS: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12-0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3-58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. CONCLUSION: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. TRIAL REGISTRATION NUMBER: ACTRN12615001183572, 03/11/2015, retrospectively registered.

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1-59.3%). The median length of treatment escalation-free survival over the entire follow-up period was 27.1 months (95% CI; 21.8-29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08-0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4-5 vs. 1-3 initial lesions. A prostate-specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation.

Background: Serially transplantable patient-derived xenografts (PDXs) are invaluable preclinical models for studying tumor biology and evaluating therapeutic agents. As these models are challenging to establish from prostate cancer specimens, the ability to preserve them through cryopreservation has several advantages for ongoing research. Despite this, there is still uncertainty about the ability to cryopreserve PDXs of prostate cancer. This study compared three different cryopreservation protocols to identify a method that can be used to reproducibly cryopreserve a diverse cohort of prostate cancer PDX models. Method(s): One serially transplantable prostate cancer PDX from the Melbourne Urological Research Alliance cohort was used to compare three cryopreservation protocols: slow freezing in fetal calf serum (FCS) with 10% dimethyl sulfoxide (DMSO), FCS with 10% DMSO supplemented with the Rho-associated kinase (ROCK) inhibitor Y-27632 and vitrification. The efficiency of the slow freezing protocols was then assessed in 17 additional prostate cancer PDXs. Following cryopreservation, PDXs were re-established in host mice that were either intact and supplemented with testosterone or castrated. Graft take rate, tumor growth, histological features, and transcriptome profiles before and after cryopreservation were compared. Result(s): Slow freezing maintained the viability and histological features of prostate cancer PDXs, and the addition of a ROCK inhibitor increased their growth following cryopreservation. Using the slow freezing method, we re-established 100% of PDXs grown in either testosterone-supplemented or castrated host mice. Importantly, the long-term tumor growth rate and transcriptome profile were maintained following cryopreservation. Conclusion(s): This study has identified a protocol to reliably cryopreserve and re-establish a diverse cohort of serially transplantable PDXs of prostate cancer. This study has the potential to significantly improve the prac

Introduction and Objectives: Prostate specific membrane antigen (PSMA) ligands in positron emission tomography (PET) imaging have shown superior results when compared to traditional imaging in prostate cancer. Simultaneous PSMA PET/MRI is an emerging modality yielding promising results in detection and staging, although scant published evidence is available. We compared the diagnostic accuracy of multiparametric MRI, PSMA PET/MRI and PSMA PET/CT to wholemount histopathology for the localisation of primary prostate cancer. Method(s): A local prospective database for patients who underwent MRI was used. 13 patients underwent multiparametric MRI, transperineal prostate biopsy, PSMA PET/ CT, PSMA PET/MRI and subsequent radical prostatectomy with whole-mount histopathology. Imaging was reported with Prostate Imaging Reporting and Data System sector maps. These were individually evaluated by dividing the prostate into 12 sectors; apex/mid/base in the transverse plane, left/right in the sagittal plane, and anterior/posterior in the coronal plane. Result(s): Whole-mount histopathology revealed significant cancer in 13 patients, present in 59 of 156 sectors, with significant cancer defined as greater than or equal to Gleason 3 + 4 = 7 (Grade Group 2). MRI detected true positives in 31 of 36 MRI positive sectors and true negatives in 92 of 120 MRI negatives sectors, conferring a sensitivity and specificity of 51% and 95% respectively. PET/CT detected true positives in 25 of 32 PSMA avid sectors and true negatives in 90 of 124 PSMA non-avid sectors, conferring a sensitivity (Table pesented) and specificity of 42% and 93% respectively. PET/MRI detected true positives in 32 of 36 PSMA avid sectors and true negatives in 93 of 120 PSMA non-avid sectors, conferring a sensitivity and specificity of 54% and 96% respectively. The overall accuracy of all 3 modalities respectively were 78%, 74% and 80%. Conclusion(s): In this case-series involving highly selected patients undergoing pro

Introduction and Objectives: PSMA PET/ CT has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting. However, there is little data published on the role of PSMA PET/CT in detecting and diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for (Table presented) the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy, and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3 + 4 = 7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. 239 patients subsequently underwent both biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 64.9% and 87.1%, 70.3%. Conclusion(s): In this highly-selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT for staging as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. It is proposed that PSMA PET may be used in both diagnosis of primary cancers and staging, although costeffectiveness in this dual role warrants further investigation. Higher sensitivity achieved by P

Background: Serially transplantable patient-derived xenografts (PDXs) are invaluable preclinical models for studying tumor biology and evaluating therapeutic agents. As these models are challenging to establish from prostate cancer specimens, the ability to preserve them through cryopreservation has several advantages for ongoing research. Despite this, there is still uncertainty about the ability to cryopreserve PDXs of prostate cancer. This study compared three different cryopreservation protocols to identify a method that can be used to reproducibly cryopreserve a diverse cohort of prostate cancer PDX models. Method(s): One serially transplantable prostate cancer PDX from the Melbourne Urological Research Alliance cohort was used to compare three cryopreservation protocols: slow freezing in fetal calf serum (FCS) with 10% dimethyl sulfoxide (DMSO), FCS with 10% DMSO supplemented with the Rho-associated kinase (ROCK) inhibitor Y-27632 and vitrification. The efficiency of the slow freezing protocols was then assessed in 17 additional prostate cancer PDXs. Following cryopreservation, PDXs were re-established in host mice that were either intact and supplemented with testosterone or castrated. Graft take rate, tumor growth, histological features, and transcriptome profiles before and after cryopreservation were compared. Result(s): Slow freezing maintained the viability and histological features of prostate cancer PDXs, and the addition of a ROCK inhibitor increased their growth following cryopreservation. Using the slow freezing method, we re-established 100% of PDXs grown in either testosterone-supplemented or castrated host mice. Importantly, the long-term tumor growth rate and transcriptome profile were maintained following cryopreservation. Conclusion(s): This study has identified a protocol to reliably cryopreserve and re-establish a diverse cohort of serially transplantable PDXs of prostate cancer. This study has the potential to significantly improve the prac

Introduction and Objectives: Prostate specific membrane antigen (PSMA) ligands in positron emission tomography (PET) imaging have shown superior results when compared to traditional imaging in prostate cancer. Simultaneous PSMA PET/MRI is an emerging modality yielding promising results in detection and staging, although scant published evidence is available. We compared the diagnostic accuracy of multiparametric MRI, PSMA PET/MRI and PSMA PET/CT to wholemount histopathology for the localisation of primary prostate cancer. Method(s): A local prospective database for patients who underwent MRI was used. 13 patients underwent multiparametric MRI, transperineal prostate biopsy, PSMA PET/ CT, PSMA PET/MRI and subsequent radical prostatectomy with whole-mount histopathology. Imaging was reported with Prostate Imaging Reporting and Data System sector maps. These were individually evaluated by dividing the prostate into 12 sectors; apex/mid/base in the transverse plane, left/right in the sagittal plane, and anterior/posterior in the coronal plane. Result(s): Whole-mount histopathology revealed significant cancer in 13 patients, present in 59 of 156 sectors, with significant cancer defined as greater than or equal to Gleason 3 + 4 = 7 (Grade Group 2). MRI detected true positives in 31 of 36 MRI positive sectors and true negatives in 92 of 120 MRI negatives sectors, conferring a sensitivity and specificity of 51% and 95% respectively. PET/CT detected true positives in 25 of 32 PSMA avid sectors and true negatives in 90 of 124 PSMA non-avid sectors, conferring a sensitivity (Table pesented) and specificity of 42% and 93% respectively. PET/MRI detected true positives in 32 of 36 PSMA avid sectors and true negatives in 93 of 120 PSMA non-avid sectors, conferring a sensitivity and specificity of 54% and 96% respectively. The overall accuracy of all 3 modalities respectively were 78%, 74% and 80%. Conclusion(s): In this case-series involving highly selected patients undergoing pro

Introduction and Objectives: PSMA PET/ CT has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting. However, there is little data published on the role of PSMA PET/CT in detecting and diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for (Table presented) the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy, and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3 + 4 = 7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. 239 patients subsequently underwent both biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 64.9% and 87.1%, 70.3%. Conclusion(s): In this highly-selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT for staging as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. It is proposed that PSMA PET may be used in both diagnosis of primary cancers and staging, although costeffectiveness in this dual role warrants further investigation. Higher sensitivity achieved by P

BACKGROUND: Serially transplantable patient-derived xenografts (PDXs) are invaluable preclinical models for studying tumor biology and evaluating therapeutic agents. As these models are challenging to establish from prostate cancer specimens, the ability to preserve them through cryopreservation has several advantages for ongoing research. Despite this, there is still uncertainty about the ability to cryopreserve PDXs of prostate cancer. This study compared three different cryopreservation protocols to identify a method that can be used to reproducibly cryopreserve a diverse cohort of prostate cancer PDX models. METHODS: One serially transplantable prostate cancer PDX from the Melbourne Urological Research Alliance cohort was used to compare three cryopreservation protocols: slow freezing in fetal calf serum (FCS) with 10% dimethyl sulfoxide (DMSO), FCS with 10% DMSO supplemented with the Rho-associated kinase (ROCK) inhibitor Y-27632 and vitrification. The efficiency of the slow freezing protocols was then assessed in 17 additional prostate cancer PDXs. Following cryopreservation, PDXs were re-established in host mice that were either intact and supplemented with testosterone or castrated. Graft take rate, tumor growth, histological features, and transcriptome profiles before and after cryopreservation were compared. RESULTS: Slow freezing maintained the viability and histological features of prostate cancer PDXs, and the addition of a ROCK inhibitor increased their growth following cryopreservation. Using the slow freezing method, we re-established 100% of PDXs grown in either testosterone-supplemented or castrated host mice. Importantly, the long-term tumor growth rate and transcriptome profile were maintained following cryopreservation. CONCLUSION: This study has identified a protocol to reliably cryopreserve and re-establish a diverse cohort of serially transplantable PDXs of prostate cancer. This study has the potential to significantly improve the practicalit

Objectives: There is little research assessing the impact of providing men with information about prostate cancer (PCa) treatment options at time of referral for a prostate biopsy. Study objectives were to determine whether receiving an information booklet about PCa treatment options prior to receiving biopsy results was acceptable to patients, and if receiving this information influenced levels of anxiety, depression, distress and treatment decisional conflict. Method(s): Patients undergoing prostate biopsy were randomised to receive either a standard biopsy instruction sheet (Control) or an information booklet about PCa treatment options in addition to the instruction sheet (Intervention). Ninetyeight patients completed validated depression, anxiety, distress and decisional conflict measures pre-biopsy and after receiving their biopsy results. Scores from baseline to follow-up were compared for both groups using mixed model repeated measures analysis. Result(s): There were no significant differences between groups in terms of changes in psychological symptoms from baseline to follow-up (all p > 0.05) and in decisional conflict post-diagnosis. Control group patients receiving positive biopsy results reported an increase in distress (p = 0.031) and depression scores (p = 0.046) from pre- to post-biopsy. Intervention group patients receiving positive biopsy results showed no significant change in psychological symptoms. 87% of patients reported that the resource made it easier to understand subsequent explanation of treatment options. Conclusion(s): Findings support the provision of information regarding PCa treatment options at time of referral for a biopsy. Patients did not experience increased psychological distress as a result of the intervention and preferred to be given this information prior to their biopsy.

Introduction & Objective: PSMA PET/ CT demonstrates superior sensitivity in staging prostate cancer compared to traditional modalities and seen a high degree of utilisation in Australia1. However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for detecting clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July-2013 to December- 2017. All patients who underwent MRI, subsequent transperineal biopsy, and PSMA PET/CT for initial staging were included, with significant cancer defined as greater than or equal to ISUP Grade Group 2. Result(s): 2,283 patients underwent prostate MRI. 239 patients subsequently underwent biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancers, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local prostate PSMA avidity, compared to 174 positive (PIRADS 4/5) MRI scans. MRI detected fewer insignificant cancers, but more false- negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 18.9% and 86.1%, 70.3% (p < 0.05). Conclusion(s): In this highly-selected cohort of patients, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual-role warrants further investigation. Higher sensitivity achieved by PET/CT comes at the expense of detecting clinically insignificant disease, evidenced by higher false-positive rates. Furthermore, soft-tissue resolution is inferior to MRI.

Background: The intractability of castration-resistant prostate cancer (CRPC) is exacerbated by tumour heterogeneity, including diverse alterations to the androgen receptor (AR) axis and AR-independent phenotypes. The availability of additional models encompassing this heterogeneity would facilitate the identification of more effective therapies for CRPC. Objective(s): To discover therapeutic strategies by exploiting patient-derived models that exemplify the heterogeneity of CRPC. Design, setting, and participants: Four new patient-derived xenografts (PDXs) were established from independent metastases of two patients and characterised using integrative genomics. A panel of rationally selected drugs was tested using an innovative ex vivo PDX culture system. Intervention(s): The following drugs were evaluated: AR signalling inhibitors (enzalutamide and galeterone), a PARP inhibitor (talazoparib), a chemotherapeutic (cisplatin), a CDK4/6 inhibitor (ribociclib), bromodomain and extraterminal (BET) protein inhibitors (iBET151 and JQ1), and inhibitors of ribosome biogenesis/function (RNA polymerase I inhibitor CX-5461 and pan-PIM kinase inhibitor CX-6258). Outcome measurements and statistical analysis: Drug efficacy in ex vivo cultures of PDX tissues was evaluated using immunohistochemistry for Ki67 and cleaved caspase-3 levels. Candidate drugs were also tested for antitumour efficacy in vivo, with tumour volume being the primary endpoint. Two-tailed t tests were used to compare drug and control treatments. Results and limitations: Integrative genomics revealed that the new PDXs exhibited heterogeneous mechanisms of resistance, including known and novel AR mutations, genomic structural rearrangements of the AR gene, and a neuroendocrine-like AR-null phenotype. Despite their heterogeneity, all models were sensitive to the combination of ribosome-targeting agents CX-5461 and CX-6258. Conclusion(s): This study demonstrates that ribosome-targeting drugs may be effective again

Objective: Both 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and multiparametric MRI (mpMRI) are emerging imaging modalities in the diagnostic pathway of prostate cancer. We assessed the accuracy of 68Ga- PSMA PET/CT and mpMRI in localising primary prostate cancer compared with radical prostatectomy (RP) specimens. Method(s): Retrospective analysis of the records of 88 men who underwent both 68Ga-PSMA PET/CT and mpMRI prior to RP between 2016 and 2018. Index tumour was defined as the lesion with highest standardised uptake value (SUVmax) on 68Ga- PSMA PET/CT, highest PIRADS score on mpMRI, and highest ISUP grade group on RP histopathology. All other lesions found on imaging were defined as non-index lesions. Accurate tumour localisation included correctly identifying sextant location compared with RP specimen. Descriptive statistics and McNemar's test were used. Result(s): 68Ga-PSMA PET/CT accurately localised index tumour in 71 (80.7%) men. In a further 7 men (7.95%), index tumour on RP corresponded with non-index lesions on 68Ga-PSMA PET/CT. mpMRI accurately localised index tumour in 74 (84.1%) men. Correct side was identified in 81 (92.1%) men. There was no significant difference between overall localisation of index tumour using 68Ga-PSMA PET/ CT (80.7%) and mpMRI (84.1%) (p = 0.664). 6 (6.82%) men had no avidity on 68Ga-PSMA PET/CT and 3 (3.41%) men had no lesion on mpMRI despite tumour on RP pathology (p = 0.450). Conclusion(s): There is no significant difference in tumour localisation of primary prostate cancer between 68Ga-PSMA PET/ CT and mpMRI, despite a trend of greater accuracy using the latter. Further studies are required to assess the diagnostic accuracy of 68Ga-PSMA PET/CT and the value of a combined PET/MRI model.

Objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting.1 However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multi-parametric MRI for the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3+4=7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. Two-hundred thirty-nine patients subsequently underwent both biopsy and PSMA PET/CT. Two hundred biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI, respectively, were 93.6%, 18.9% and 86.1%, 70.3% (P < 0.05). Conclusion(s): In this highly selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual role warrants further inves

Objective: Prostate specific membrane antigen ligands in PET imaging show superior results compared to traditional prostate cancer imaging techniques1. Simultaneous PSMA PET/MR is an emerging modality yielding promising results. We compared the diagnostic accuracy of multiparametric MRI, PSMA PET/ MR and PSMA PET/CT to whole-mount histopathology for localization of primary prostate cancer. Method(s): A prospective database (REDCap-Monash) for patients who underwent MRI in our group urology practice since 2013 was used. 8 patients underwent MRI, PSMA PET/CT, PSMA PET/MR and subsequent radical prostatectomy with whole-mount histopathology. Imaging was reported based on PIRADS Sector Maps, with results analysed by dividing the prostate into 12 sectors; apex/ mid/base in the transverse plane, left/right in the sagittal plane, and anterior/posterior in the coronal plane. Result(s): Whole-mount histopathology revealed significant cancer in 8 patients, with tumour foci detected in 46/96 sectors, with significant cancer defined as greater than or equal to Gleason 3 + 4 = 7. MRI detected lesions in 20 sectors (19 involving tumour foci), no lesion in 76 sectors (27 involving tumour foci). PET/CT demonstrated avidity in 32 sectors (21 involving tumour foci), no avidity in 64 sectors (25 involving tumour foci). PET/MR demonstrated avidity in 22 sectors (all involving tumour foci), no avidity in 74 sectors (24 involving tumour foci). The overall accuracies were 71%, 63% and 75% respectively. Conclusion(s): In this case-series involving highly selected patients, PET/MR outperformed both MRI and PET/CT in accurately detecting significant primary prostate cancer. As a diagnostic technique, pelvic PET/MR is an emerging modality, and as such requires further investigation and cost-effectiveness analysis.

Objective: 68Ga-prostate-specific membrane antigen (PSMA) PET/CT has emerged as a valuable tool in the diagnosis of prostate cancer. Maximum standardised uptake value (SUVmax) is used to identify tumour foci within the prostate. Our objective was to correlate SUVmax with tumour grade on prostate biopsy. Method(s): Retrospective analysis of the records of 151 men who underwent 68Ga- PSMA PET/CT prior to prostate biopsy between 2016 and 2018. SUVmax on PET/ CT and ISUP Grade Group (GG) on biopsy were collected. Clinically significant disease was defined as GG 3-5. Receiver operating characteristic (ROC) curve analysis was used to identify SUVmax thresholds optimising predictive value for GG 3-5 disease. Result(s): Mean age was 67.2 (+/-1.39) years and mean PSA 9.77 (+/-1.77) ng/mL. There was no significant difference between mean SUVmax of GG1 (3.49 +/- 0.71) compared to GG2 (4.01 +/- 0.96) tumours (p = 0.850), or between GG3 (7.92 +/- 1.72), GG4 (6.48 +/- 2.54) and GG5 (10.65 +/- 3.49) tumours (p = 0.491, 0.152). However, mean SUVmax of GG 3-5 tumours (8.34 +/- 1.37) was significantly greater than that of GG 1-2 tumours (4.46 +/- 0.54) (p < 0.001). SUVmax 4.35 was identified as an ideal threshold, with sensitivity of 82.8% and specificity of 69.0%. Positive predictive value at this threshold was 66.3% and negative predictive value 84.5%. Conclusion(s): High grade tumours are associated with significantly higher SUVmax on 68Ga-PSMA PET/CT than lower grade tumours. Using a SUVmax threshold of 4.35 gives a high sensitivity and high negative predictive value for clinically significant disease. 68Ga-PSMA PET/CT may prove useful in active surveillance, and further studies are required to assess its role alongside prostate MRI.

Background: The intractability of castration-resistant prostate cancer (CRPC) is exacerbated by tumour heterogeneity, including diverse alterations to the androgen receptor (AR) axis and AR-independent phenotypes. The availability of additional models encompassing this heterogeneity would facilitate the identification of more effective therapies for CRPC. Objective(s): To discover therapeutic strategies by exploiting patient-derived models that exemplify the heterogeneity of CRPC. Design, setting, and participants: Four new patient-derived xenografts (PDXs) were established from independent metastases of two patients and characterised using integrative genomics. A panel of rationally selected drugs was tested using an innovative ex vivo PDX culture system. Intervention(s): The following drugs were evaluated: AR signalling inhibitors (enzalutamide and galeterone), a PARP inhibitor (talazoparib), a chemotherapeutic (cisplatin), a CDK4/6 inhibitor (ribociclib), bromodomain and extraterminal (BET) protein inhibitors (iBET151 and JQ1), and inhibitors of ribosome biogenesis/function (RNA polymerase I inhibitor CX-5461 and pan-PIM kinase inhibitor CX-6258). Outcome measurements and statistical analysis: Drug efficacy in ex vivo cultures of PDX tissues was evaluated using immunohistochemistry for Ki67 and cleaved caspase-3 levels. Candidate drugs were also tested for antitumour efficacy in vivo, with tumour volume being the primary endpoint. Two-tailed t tests were used to compare drug and control treatments. Results and limitations: Integrative genomics revealed that the new PDXs exhibited heterogeneous mechanisms of resistance, including known and novel AR mutations, genomic structural rearrangements of the AR gene, and a neuroendocrine-like AR-null phenotype. Despite their heterogeneity, all models were sensitive to the combination of ribosome-targeting agents CX-5461 and CX-6258. Conclusion(s): This study demonstrates that ribosome-targeting drugs may be effective again

Objectives: There is little research assessing the impact of providing men with information about prostate cancer (PCa) treatment options at time of referral for a prostate biopsy. Study objectives were to determine whether receiving an information booklet about PCa treatment options prior to receiving biopsy results was acceptable to patients, and if receiving this information influenced levels of anxiety, depression, distress and treatment decisional conflict. Method(s): Patients undergoing prostate biopsy were randomised to receive either a standard biopsy instruction sheet (Control) or an information booklet about PCa treatment options in addition to the instruction sheet (Intervention). Ninetyeight patients completed validated depression, anxiety, distress and decisional conflict measures pre-biopsy and after receiving their biopsy results. Scores from baseline to follow-up were compared for both groups using mixed model repeated measures analysis. Result(s): There were no significant differences between groups in terms of changes in psychological symptoms from baseline to follow-up (all p > 0.05) and in decisional conflict post-diagnosis. Control group patients receiving positive biopsy results reported an increase in distress (p = 0.031) and depression scores (p = 0.046) from pre- to post-biopsy. Intervention group patients receiving positive biopsy results showed no significant change in psychological symptoms. 87% of patients reported that the resource made it easier to understand subsequent explanation of treatment options. Conclusion(s): Findings support the provision of information regarding PCa treatment options at time of referral for a biopsy. Patients did not experience increased psychological distress as a result of the intervention and preferred to be given this information prior to their biopsy.

Introduction & Objective: PSMA PET/ CT demonstrates superior sensitivity in staging prostate cancer compared to traditional modalities and seen a high degree of utilisation in Australia1. However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multiparametric MRI for detecting clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July-2013 to December- 2017. All patients who underwent MRI, subsequent transperineal biopsy, and PSMA PET/CT for initial staging were included, with significant cancer defined as greater than or equal to ISUP Grade Group 2. Result(s): 2,283 patients underwent prostate MRI. 239 patients subsequently underwent biopsy and PSMA PET/CT. 202 biopsies (84.5%) showed significant cancer. Of the non-significant cancers, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local prostate PSMA avidity, compared to 174 positive (PIRADS 4/5) MRI scans. MRI detected fewer insignificant cancers, but more false- negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI respectively were 93.6%, 18.9% and 86.1%, 70.3% (p < 0.05). Conclusion(s): In this highly-selected cohort of patients, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual-role warrants further investigation. Higher sensitivity achieved by PET/CT comes at the expense of detecting clinically insignificant disease, evidenced by higher false-positive rates. Furthermore, soft-tissue resolution is inferior to MRI.

Objective: Both 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and multiparametric MRI (mpMRI) are emerging imaging modalities in the diagnostic pathway of prostate cancer. We assessed the accuracy of 68Ga- PSMA PET/CT and mpMRI in localising primary prostate cancer compared with radical prostatectomy (RP) specimens. Method(s): Retrospective analysis of the records of 88 men who underwent both 68Ga-PSMA PET/CT and mpMRI prior to RP between 2016 and 2018. Index tumour was defined as the lesion with highest standardised uptake value (SUVmax) on 68Ga- PSMA PET/CT, highest PIRADS score on mpMRI, and highest ISUP grade group on RP histopathology. All other lesions found on imaging were defined as non-index lesions. Accurate tumour localisation included correctly identifying sextant location compared with RP specimen. Descriptive statistics and McNemar's test were used. Result(s): 68Ga-PSMA PET/CT accurately localised index tumour in 71 (80.7%) men. In a further 7 men (7.95%), index tumour on RP corresponded with non-index lesions on 68Ga-PSMA PET/CT. mpMRI accurately localised index tumour in 74 (84.1%) men. Correct side was identified in 81 (92.1%) men. There was no significant difference between overall localisation of index tumour using 68Ga-PSMA PET/ CT (80.7%) and mpMRI (84.1%) (p = 0.664). 6 (6.82%) men had no avidity on 68Ga-PSMA PET/CT and 3 (3.41%) men had no lesion on mpMRI despite tumour on RP pathology (p = 0.450). Conclusion(s): There is no significant difference in tumour localisation of primary prostate cancer between 68Ga-PSMA PET/ CT and mpMRI, despite a trend of greater accuracy using the latter. Further studies are required to assess the diagnostic accuracy of 68Ga-PSMA PET/CT and the value of a combined PET/MRI model.

Objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has demonstrated superior sensitivity in detecting prostate cancer metastases compared to traditional staging modalities and seen a high degree of utilisation in the Australian setting.1 However, there is little data published on the role of PSMA PET/CT in diagnosing primary prostate cancer. We compared the accuracy of PSMA PET/CT to multi-parametric MRI for the detection of clinically significant primary prostate cancer. Method(s): A local prospective database (REDCap-Monash) was maintained on patients who underwent MRI in our group urology practice from July 2013 to December 2017. All patients who had an MRI for diagnosis of prostate cancer, subsequent transperineal biopsy and a PSMA PET/CT for initial staging were included, with significant cancer being defined as greater than or equal to Gleason 3+4=7 (ISUP Grade Group 2). Result(s): The database contained 2283 patients who underwent prostate MRI. Two-hundred thirty-nine patients subsequently underwent both biopsy and PSMA PET/CT. Two hundred biopsies (84.5%) showed significant cancer. Of the non-significant cancer cases, 21 (8.8%) revealed Grade Group 1 lesions and 16 (6.7%) were benign. For significant cancers, 189 PSMA PET/CT scans demonstrated local PSMA avidity in the prostate, compared to 174 positive (PIRADS 4 or 5) MRI scans. MRI detected fewer insignificant cancers, but resulted in more false negatives. Overall, sensitivity and specificity for PSMA PET/CT and MRI, respectively, were 93.6%, 18.9% and 86.1%, 70.3% (P < 0.05). Conclusion(s): In this highly selected cohort of patients undergoing prostate MRI, transperineal biopsy and PSMA PET/CT as part of clinical practice, PSMA PET/CT outperformed MRI in detecting clinically significant primary prostate cancer. This can enhance its uses, in detecting and staging primary cancers, although cost-effectiveness in this dual role warrants further inves

Objective: Prostate specific membrane antigen ligands in PET imaging show superior results compared to traditional prostate cancer imaging techniques1. Simultaneous PSMA PET/MR is an emerging modality yielding promising results. We compared the diagnostic accuracy of multiparametric MRI, PSMA PET/ MR and PSMA PET/CT to whole-mount histopathology for localization of primary prostate cancer. Method(s): A prospective database (REDCap-Monash) for patients who underwent MRI in our group urology practice since 2013 was used. 8 patients underwent MRI, PSMA PET/CT, PSMA PET/MR and subsequent radical prostatectomy with whole-mount histopathology. Imaging was reported based on PIRADS Sector Maps, with results analysed by dividing the prostate into 12 sectors; apex/ mid/base in the transverse plane, left/right in the sagittal plane, and anterior/posterior in the coronal plane. Result(s): Whole-mount histopathology revealed significant cancer in 8 patients, with tumour foci detected in 46/96 sectors, with significant cancer defined as greater than or equal to Gleason 3 + 4 = 7. MRI detected lesions in 20 sectors (19 involving tumour foci), no lesion in 76 sectors (27 involving tumour foci). PET/CT demonstrated avidity in 32 sectors (21 involving tumour foci), no avidity in 64 sectors (25 involving tumour foci). PET/MR demonstrated avidity in 22 sectors (all involving tumour foci), no avidity in 74 sectors (24 involving tumour foci). The overall accuracies were 71%, 63% and 75% respectively. Conclusion(s): In this case-series involving highly selected patients, PET/MR outperformed both MRI and PET/CT in accurately detecting significant primary prostate cancer. As a diagnostic technique, pelvic PET/MR is an emerging modality, and as such requires further investigation and cost-effectiveness analysis.

Objective: 68Ga-prostate-specific membrane antigen (PSMA) PET/CT has emerged as a valuable tool in the diagnosis of prostate cancer. Maximum standardised uptake value (SUVmax) is used to identify tumour foci within the prostate. Our objective was to correlate SUVmax with tumour grade on prostate biopsy. Method(s): Retrospective analysis of the records of 151 men who underwent 68Ga- PSMA PET/CT prior to prostate biopsy between 2016 and 2018. SUVmax on PET/ CT and ISUP Grade Group (GG) on biopsy were collected. Clinically significant disease was defined as GG 3-5. Receiver operating characteristic (ROC) curve analysis was used to identify SUVmax thresholds optimising predictive value for GG 3-5 disease. Result(s): Mean age was 67.2 (+/-1.39) years and mean PSA 9.77 (+/-1.77) ng/mL. There was no significant difference between mean SUVmax of GG1 (3.49 +/- 0.71) compared to GG2 (4.01 +/- 0.96) tumours (p = 0.850), or between GG3 (7.92 +/- 1.72), GG4 (6.48 +/- 2.54) and GG5 (10.65 +/- 3.49) tumours (p = 0.491, 0.152). However, mean SUVmax of GG 3-5 tumours (8.34 +/- 1.37) was significantly greater than that of GG 1-2 tumours (4.46 +/- 0.54) (p < 0.001). SUVmax 4.35 was identified as an ideal threshold, with sensitivity of 82.8% and specificity of 69.0%. Positive predictive value at this threshold was 66.3% and negative predictive value 84.5%. Conclusion(s): High grade tumours are associated with significantly higher SUVmax on 68Ga-PSMA PET/CT than lower grade tumours. Using a SUVmax threshold of 4.35 gives a high sensitivity and high negative predictive value for clinically significant disease. 68Ga-PSMA PET/CT may prove useful in active surveillance, and further studies are required to assess its role alongside prostate MRI.

BACKGROUND: To compare perioperative, renal and oncological outcomes after robotic-assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours. METHODS: All partial nephrectomies performed at a Metropolitan Urology Centre between 2010 and 2016 were analysed. Baseline data was collected for patient demographics, tumour characteristics (tumour size, laterality and polarity, RENAL scores), and perioperative variables (e.g. warm ischaemic time, operation time, estimated blood loss (EBL), length of stay). Tumour characteristics included malignancy, clinical stage, Fuhrman nuclear grade and surgical margin status. Day-1 post-operative serum creatinine, estimated glomerular filtration rate (eGFR) and 6-month eGFR stage were used for assessing renal function. RESULTS: Two hundred patients underwent partial nephrectomy between 2010 and 2016 (n = 200; 55 OPN versus 145 RAPN). Baseline data was similar between groups, except for lower age (P = 0.0001) and higher RENAL scores (P = 0.001) in the RAPN group. RAPN demonstrated significantly lower complication rates (P = 0.015), lesser EBL (P = <0.0001), shorter hospital stays (P = <0.001) and reduced positive tumour resection margins (P = 0.039). There was no significant difference in mean operation time between RAPN and OPN (137.2 (±48.0) OPN versus 146.07 (±35.91) RAPN; P = 0.16). No statistical difference was shown for post-operative eGFR stage between groups at Day-1 and 6-month post-surgery (P = 0.15 and P = 0.861, respectively). CONCLUSION: We present the largest reported Australian series on partial nephrectomy, confirming that a robotic-assisted approach is equivalent to OPN, with reduced complications, EBL, length of hospital stays and fewer positive margins, even when resecting more complex tumours.

BACKGROUND: The objective of this study was to compare pain intensity in patients undergoing transrectal ultrasound (TRUS)-guided biopsy of the prostate with Penthrox alone compared with Penthrox plus periprostatic infiltration of local analgesia (PILA). METHOD: Seventy-two subjects participated in this study after receiving appropriate education. Forty-two patients self-administered inhaled Penthrox (3mL methoxyflurane) alone for analgesia (Group A), followed by 30 patients who self-administered Penthrox and received PILA with 5mL of 2% lignocaine. All subjects had TRUS biopsy performed. Immediately after the procedure, patients were asked to rate their pain intensity using a numerical verbal rating scale from 0 to 10. RESULTS: Baseline characteristics of the two groups were similar. Patients in Group B reported significantly lower post TRUS biopsy median pain intensity of 2 (1-3) compared with Group A subjects who reported a median post TRUS biopsy pain intensity of 3 (2-5) (P = 0.014). A total of 72 men underwent TRUS-guided biopsy. All patients indicated they would be happy to have another TRUS-guided prostate biopsy in the future. CONCLUSION: Our study shows that Penthrox plus PILA shows promise as an efficacious and easily tolerated analgesic technique for outpatient TRUS biopsy, keeping resource use to a minimum. Planning for a multi-centre, double-blind randomized control trial comparing Penthrox plus PILA with PILA alone is presently underway.Copyright © 2015 Royal Australasian College of Surgeons.

BACKGROUND: The objective of this study was to compare pain intensity in patients undergoing transrectal ultrasound (TRUS)-guided biopsy of the prostate with Penthrox alone compared with Penthrox plus periprostatic infiltration of local analgesia (PILA). METHOD: Seventy-two subjects participated in this study after receiving appropriate education. Forty-two patients self-administered inhaled Penthrox (3mL methoxyflurane) alone for analgesia (Group A), followed by 30 patients who self-administered Penthrox and received PILA with 5mL of 2% lignocaine. All subjects had TRUS biopsy performed. Immediately after the procedure, patients were asked to rate their pain intensity using a numerical verbal rating scale from 0 to 10. RESULTS: Baseline characteristics of the two groups were similar. Patients in Group B reported significantly lower post TRUS biopsy median pain intensity of 2 (1-3) compared with Group A subjects who reported a median post TRUS biopsy pain intensity of 3 (2-5) (P = 0.014). A total of 72 men underwent TRUS-guided biopsy. All patients indicated they would be happy to have another TRUS-guided prostate biopsy in the future. CONCLUSION: Our study shows that Penthrox plus PILA shows promise as an efficacious and easily tolerated analgesic technique for outpatient TRUS biopsy, keeping resource use to a minimum. Planning for a multi-centre, double-blind randomized control trial comparing Penthrox plus PILA with PILA alone is presently underway.Copyright © 2015 Royal Australasian College of Surgeons.

INTRODUCTION & OBJECTIVES: Transperineal prostate biopsy (TPB) has been proposed as a safer more sensitive method for obtaining prostate gland biopsy. Herein we present our technique and report the outcomes and safety profile of TPB utilising our prospective Victorian Transperineal Biopsy Collaboration (VTBC) database. MATERIAL & METHODS: The VTBC is a multi-institutional registry collecting data prospectively from four contributing institutions across Melbourne, Australia. The database is ethics approved at each institution and data collected is based on the minimum dataset published by the Ginsburg Study Group. We present a video of our technique and retrospectively analyse the outcomes of men undergoing TPB. RESULT(S): Our technique for performing TPB, using the Ginsburg protocol, is demonstrated in this video. A total of 1108 men underwent TPB between June 2010 and June 2015, with 894 having adequate histological data for analysis. The indications for TPB were primary biopsy (44.4%), repeat biopsy in the setting of previous negative TRUS biopsy (19%) and confirmatory biopsy for men on active surveillance (36.6%). The mean cohort age was 63.5 (range 41 - 87) and mean pre-biopsy PSA was 9.05 (range 0.14 - 85). In 397 men undergoing TPB as initial biopsy, 328/397(82.6%) were diagnosed with prostate cancer and 215/397 (54.1%) were diagnosed with Gleason >= 7 disease. In 170 men with a prior negative TRUS biopsy, 51/170 (30%) were found to have prostate cancer and 35/170 (20.5%) were diagnosed with Gleason >= 7 disease. Of 327 patients on active surveillance, 137/327 (43%) were upstaged to Gleason >= 7 disease. Overall 230 (25.7%) men were diagnosed with an anterior tumour. The overall rate of acute urinary retention was 3.2%. Only 3(0.3%) patients in the cohort required hospital admission due to biopsy related infection. CONCLUSION(S): The VTBC is the largest reported database of patients having TPB in Australia and New Zealand. The current results show that TPB is

INTRODUCTION & OBJECTIVES: Transperineal prostate biopsy (TPB) has been proposed as a safer more sensitive method for obtaining prostate gland biopsy. Herein we present our technique and report the outcomes and safety profile of TPB utilising our prospective Victorian Transperineal Biopsy Collaboration (VTBC) database. MATERIAL & METHODS: The VTBC is a multi-institutional registry collecting data prospectively from four contributing institutions across Melbourne, Australia. The database is ethics approved at each institution and data collected is based on the minimum dataset published by the Ginsburg Study Group. We present a video of our technique and retrospectively analyse the outcomes of men undergoing TPB. RESULT(S): Our technique for performing TPB, using the Ginsburg protocol, is demonstrated in this video. A total of 1108 men underwent TPB between June 2010 and June 2015, with 894 having adequate histological data for analysis. The indications for TPB were primary biopsy (44.4%), repeat biopsy in the setting of previous negative TRUS biopsy (19%) and confirmatory biopsy for men on active surveillance (36.6%). The mean cohort age was 63.5 (range 41 - 87) and mean pre-biopsy PSA was 9.05 (range 0.14 - 85). In 397 men undergoing TPB as initial biopsy, 328/397(82.6%) were diagnosed with prostate cancer and 215/397 (54.1%) were diagnosed with Gleason >= 7 disease. In 170 men with a prior negative TRUS biopsy, 51/170 (30%) were found to have prostate cancer and 35/170 (20.5%) were diagnosed with Gleason >= 7 disease. Of 327 patients on active surveillance, 137/327 (43%) were upstaged to Gleason >= 7 disease. Overall 230 (25.7%) men were diagnosed with an anterior tumour. The overall rate of acute urinary retention was 3.2%. Only 3(0.3%) patients in the cohort required hospital admission due to biopsy related infection. CONCLUSION(S): The VTBC is the largest reported database of patients having TPB in Australia and New Zealand. The current results show that TPB is

Introduction and Objectives: Standard trans-rectal biopsies of the prostate underclassify prostate cancer, making the selection of patients for active surveillance more difficult. Previous studies from our group have shown that the biopsy undergrades prostate cancer in 35% of cases compared to the final radical prostatectomy specimens, with 38% of cases having pT3 disease. In addition the biopsies predicted the incorrect lobe in 16% of men, and the index tumour was discordant with the site of positive margins in 54% of cases. Our objective was to determine if a pre-biopsy 3T mpMRI prostate more accurately classified the cancer, and whether the biopsy findings were more concordant with the final RP pathology. Method(s): 125 cases of men on AS were subjected to a pre-biopsy 3T mpMRI prostate, all performed by a single uro-radiologist and PIRADS scoring determined and confirmed. Pathology (both biopsy and RP) was interpreted centrally by a single uro-pathologist. 24 core trans-perineal prostate biopsy was performed pre-biopsy and if a target was identified by MRI, an additional 4 cores were taken from the target zone using cognitive fusion. If patients progressed to radical prostatectomy, the biopsy/RP pathology was compared. Result(s): Of the 74 cases classified as PIRADS 1,2 upgrading of tumour was determined in 12% of cases usually to minor foci of Gleason 3 = 4 = 7 cancer, and 95.9% of men chose to remain on AS. Of the 13 cases of PIRADS 3, 30.8% were upgraded, with 84.6% of men remaining on AS. Of the 14 cases of PIRADS 4, 21.4% were upgraded, with 71.4% remaining on AS. Of the 24 PIRADS 5 lesions upgrading was noted in 45.8% and only 8.4% remained on AS. In 58% of cases the TPB yielded the same diagnostic information to the MRI guided biopsy. In 19.4% of cases the target biopsy yielded unique information that was missed by the TPB template and in 22.6% of cases the TPB biopsy yielded results that were missed by the MRI guided biopsy. Of the 25 patients who procee

Background: Instillation of Bacillus Calmette-Guerin (BCG) into the urinary bladder (intravesical administration) decreases rates of disease recurrence after transurethral resection (TUR) of high risk, non-muscle invasive bladder cancer (NMIBC), but over 30% of people recur despite optimal adjuvant intravesical BCG. Our meta-analysis and pilot study, suggest outcomes can improve by using an adjuvant intravesical regimen including Mitomycin and BCG. Aim(s): To determine the efficacy and safety of Mitomycin in addition to BCG in patients with NMIBC Trial Design: An open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial. Primary endpoint is disease free survival (evidence of transitional cell carcinoma [TCC]) or death. Secondary endpoints are: activity (clear cystoscopy at 3 months), time to recurrence of TCC, time to progression, safety, HRQOL, overall survival, feasibility, marginal resource use. Tertiary objective is to undertake exploratory biomarker studies to predict clinical outcomes. 500 participants will provide an 85% power to detect a 10% improvement in DFS rate at 2 years from 70% on BCG alone to 80% on BCG and Mitomycin (HR 0.63) at a significance level of 0.05, allowing for 10% non-compliance. Participant(s): Adults with resected, high-risk NMIBC (high grade Ta or any grade T1) suitable for intravesical chemotherapy. Regimen: Randomisation 1:1 to intravesical BCG alone (standard): induction (weekly x 6), followed by Maintenance (monthly x 10) OR Intravesical BCG + Mitomycin (experimental): Induction (weekly x 9) followed by Maintenance (monthly x 9). Assessments: Cystoscopy, ratings of HRQL and resource use at baseline and months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48 and 60. Clinical assessments include adverse events assessment weekly during induction, then monthly before each maintenance chemotherapy instillation. Status: As of August 2015, 9 sites open in Australia with 46 participants recruited.

Introduction & Objectives: Risk factors for developing sepsis following TRUS biopsy are still poorly understood. The most likely risk factors are thought to increase the likelihood of a patient harbouring endogenous antibiotic resistant bacteria. They include recent international travel and recent antibiotic use. This study sought to investigate the prevalence of risk factors for sepsis in patients undergoing prostate biopsy and to investigate the prevalence of different prostate biopsy approaches at a large volume hospital. Method(s): Ethics approval was obtained. Telephone questionnaire was administered to men post prostate biopsy at Epworth healthcare. The questionnaire evaluated infectious complications, prior antibiotic use and recent international travel. Student T test analysis was used. Result(s): From September 2013-August 2014, 278 men were contacted. 147 (52%) underwent a transperineal biopsy (TP) and 131 (48%) underwent a transrectal biopsy. 104 (37%) reported recent overseas travel [58 (56%) TP, 46 (44%) TRUS]. Following biopsy, 11 (3.9%) patients sought medical assistance for infection related complications. 1 (0.3%) patient was readmitted with sepsis. Conclusion(s): A large proportion of men contacted travelled internationally. The majority of these men underwent TP biopsy, suggesting that urologists favour TP biopsy in recently travelled patients. Infective episodes were too low in this study to determine if overseas travel or recent antibiotic use were risk factors.

Objective To determine whether patients with normal preoperative renal function, but who possess medical risk factors for chronic kidney disease (CKD), experience poorer renal function after partial nephrectomy (PN) for renal cell carcinoma (RCC) compared with those without risk factors. Patients and Methods The effects of age, hypertension (HTN) and diabetes mellitus (DM) on estimated glomerular filtration rate (eGFR) were investigated in 488 consecutive operations for RCC performed during 2005-2012 at six Australian tertiary referral centres; 156 patients underwent PN and 332 patients underwent radical nephrectomy (RN). We used chi-squared test and binary logistic regression to analyse new-onset CKD, and multiple linear regression to investigate determinants of postoperative eGFR. Results The development of new-onset eGFR of <60 mL/min was related to undergoing RN rather than PN (risk ratio [RR] 2.7, P < 0.001), older age (RR 1.6, P < 0.001) and the presence of HTN (RR 1.6, P = 0.001) and DM (RR 1.5, P = 0.003). Patients undergoing PN were still at risk of new-onset CKD if medical risk factors were present. Whereas 7% of patients undergoing PN without CKD risk factors developed new-onset eGFR <60 mL/min, this figure increased to 24%, 30% and 42% for older age, HTN and DM, respectively. Patients with eGFR of 45-59 mL/min were more likely to progress to more severe forms of CKD and end-stage renal failure than those with eGFR of >=60 mL/min. On multivariate analysis, RN, rather than PN, age and the presence of DM (but not HTN), predicted both the development of new-onset eGFR of <60 mL/min (R2 = 0.37) and new-onset eGFR <45 mL/min (R2 = 0.42). Conclusion Patients with medical risk factors for CKD are at increased risk of progressive renal impairment despite the use of PN. Where feasible, nephron-sparing surgery should be considered for these patients.Copyright © 2015 The Authors © 2015 BJU International Published by John Wiley & Sons Ltd.

Background: A transrectal ultrasound-guided prostate biopsy (TRUS) is the current gold standard for the diagnosis of prostate cancer. The standard analgesia for a TRUS biopsy is with periprostatic infiltration of local anaesthetic (PILA). However many men still experience significant pain. We hypothesise that the addition of methoxyflurane (Penthrox) to PILA will improve the pain, discomfort and experience of the TRUS biopsy, thereby increasing men's willingness to undergo repeat TRUS prostate biopsy. Method(s): This is a multi-centre, placebo-controlled, double-blinded, centrally randomised phase 3 trial. The target population is men scheduled to undergo their first TRUS biopsy of the prostate for a raised PSA or an abnormal digital rectal examination. Participants are randomised 1:1 to inhaled methoxyflurane or placebo and stratified by age and study site. All participants are treated with PILA (2% lignocaine), injected into and around the prostate prior to the biopsy. The primary objective is to determine the effects of inhaled methoxyflurane on pain rated by participants 15 minutes after biopsy. Secondary endpoints include other aspects of the biopsy experience rated by participants, willingness to undergo a biopsy in the future, Urologist's ratings of the participant's biopsy experience, biopsy completion, frequency of specified adverse events and frequency of hospitalisation. A sample size of 420 participants provides over 85% power at the two-sided 5% level of significance to detect a 0.80 point difference in mean pain scores (on scale from 0-10) assuming a standard deviation of 2.5 whilst allowing for missing data. Patients will complete a questionnaire to document their experience of the biopsy at 5-30 minutes following the procedure and at 7-35 days after the procedure. Urologists will also complete a questionnaire on the day of the procedure. Trial recruitment is scheduled to start by the last quarter of 2015.

Background: Instillation of Bacillus Calmette-Guerin (BCG) into the urinary bladder (intravesical administration) decreases rates of disease recurrence after transurethral resection (TUR) of high risk, non-muscle invasive bladder cancer (NMIBC), but over 30% of people recur despite optimal adjuvant intravesical BCG. Our meta-analysis and pilot study, suggest outcomes can improve by using an adjuvant intravesical regimen including Mitomycin and BCG. Aim(s): To determine the efficacy and safety of Mitomycin in addition to BCG in patients with NMIBC Trial Design: An open label, randomised, stratified, 2-arm multicentre phase 3 clinical trial. Primary endpoint is disease free survival (evidence of transitional cell carcinoma [TCC]) or death. Secondary endpoints are: activity (clear cystoscopy at 3 months), time to recurrence of TCC, time to progression, safety, HRQOL, overall survival, feasibility, marginal resource use. Tertiary objective is to undertake exploratory biomarker studies to predict clinical outcomes. 500 participants will provide an 85% power to detect a 10% improvement in DFS rate at 2 years from 70% on BCG alone to 80% on BCG and Mitomycin (HR 0.63) at a significance level of 0.05, allowing for 10% non-compliance. Participant(s): Adults with resected, high-risk NMIBC (high grade Ta or any grade T1) suitable for intravesical chemotherapy. Regimen: Randomisation 1:1 to intravesical BCG alone (standard): induction (weekly x 6), followed by Maintenance (monthly x 10) OR Intravesical BCG + Mitomycin (experimental): Induction (weekly x 9) followed by Maintenance (monthly x 9). Assessments: Cystoscopy, ratings of HRQL and resource use at baseline and months 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48 and 60. Clinical assessments include adverse events assessment weekly during induction, then monthly before each maintenance chemotherapy instillation. Status: As of August 2015, 9 sites open in Australia with 46 participants recruited.

Introduction & Objectives: Risk factors for developing sepsis following TRUS biopsy are still poorly understood. The most likely risk factors are thought to increase the likelihood of a patient harbouring endogenous antibiotic resistant bacteria. They include recent international travel and recent antibiotic use. This study sought to investigate the prevalence of risk factors for sepsis in patients undergoing prostate biopsy and to investigate the prevalence of different prostate biopsy approaches at a large volume hospital. Method(s): Ethics approval was obtained. Telephone questionnaire was administered to men post prostate biopsy at Epworth healthcare. The questionnaire evaluated infectious complications, prior antibiotic use and recent international travel. Student T test analysis was used. Result(s): From September 2013-August 2014, 278 men were contacted. 147 (52%) underwent a transperineal biopsy (TP) and 131 (48%) underwent a transrectal biopsy. 104 (37%) reported recent overseas travel [58 (56%) TP, 46 (44%) TRUS]. Following biopsy, 11 (3.9%) patients sought medical assistance for infection related complications. 1 (0.3%) patient was readmitted with sepsis. Conclusion(s): A large proportion of men contacted travelled internationally. The majority of these men underwent TP biopsy, suggesting that urologists favour TP biopsy in recently travelled patients. Infective episodes were too low in this study to determine if overseas travel or recent antibiotic use were risk factors.