Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

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.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study.

PURPOSE: Our aim was to evaluate whether transperineal (TP) MRI-targeted prostate biopsy (TBx) may improve the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology ≥2, in comparison to transrectal (TR) TBx. MATERIALS AND METHODS: A multicenter retrospective cohort study comprising patients who underwent MRI-guided prostate biopsy was conducted. To address possible benefits of TP-TBx in the detection of prostate cancer (PCa) and csPCa, a cohort of patients undergoing TP-TBx were compared to patients undergoing TR-TBx. Multivariable logistic regression analyses were performed to assess predictors of PCa and csPCa detection. RESULTS: Overall, 1,936 and 3,305 patients who underwent TR-TBx vs TP-TBx at 10 referral centers were enrolled. The rate of PCa and csPCa diagnosed was higher for TP-TBx vs TR-TBx (64.0% vs 50%, p <0.01 and 49% vs 35%, p <0.01). At multivariable analysis adjusted for age, biopsy naïve/repeated biopsy, cT stage, Prostate Imaging-Reporting and Data System®, prostate volume, PSA, and number of biopsy cores targeted, TP-TBx was an independent predictor of PCa (odds ratio [OR] 1.37, 95% CI 1.08-1.72) and csPCa (1.19, 95% CI 1.12-1.50). When considering the approach according to the site of the index lesion, TP-TBx had a significantly higher likelihood than TR-TBx to detect csPCa in the apex (OR 4.81, 95% CI 1.03-6.27), transition/central zone (OR 2.67, 95% CI 1.42-5.00), and anterior zone (OR 5.62, 95% CI 1.74-8.13). CONCLUSIONS: The use of TP-TBx allows a better cancer grade definition and PCa risk assessment. This has important implication in the decision-making process and in patient counseling for further therapies.

'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

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.

Augmented deep learning model for improved quantitative accuracy of MR-based PET attenuation correction in PSMA PET-MRI prostate imaging.

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. METHODS: 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 µ-maps and the reconstructed PET images. RESULTS: 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 µ-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 µ-map in the pelvic region was 1.9% for µ-mapGAN + aug compared with 6.4% for µ-mapdixon, 5.9% for µ-mapdixon + bone, 2.1% for µ-mapU-Net and 2.0% for µ-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: The proposed technique to augment the training datasets for training of the GAN results in improved accuracy of the estimated µ-map and consequently the PET quantification compared to the state of the art.

Role of multiparametric prostate MRI in the management of prostate cancer.

INTRODUCTION: Prostate cancer has traditionally been diagnosed by an elevation in PSA or abnormal exam leading to a systematic transrectal ultrasound (TRUS)-guided biopsy. This diagnostic pathway underdiagnoses clinically significant disease while over diagnosing clinically insignificant disease. In this review, we aim to provide an overview of the recent literature regarding the role of multiparametric MRI (mpMRI) in the management of prostate cancer. MATERIALS AND METHODS: A thorough literature review was performed using PubMed to identify articles discussing use of mpMRI of the prostate in management of prostate cancer. CONCLUSION: The incorporation of mpMRI of the prostate addresses the shortcomings of the prostate biopsy while providing several other advantages. mpMRI allows some men to avoid an immediate biopsy and permits visualization of areas likely to harbor clinically significant cancer prior to biopsy to facilitate use of MR-targeted prostate biopsies. This allows for reduction in diagnosis of clinically insignificant disease as well as improved detection and better characterization of higher risk cancers, as well as the improved selection of patients for active surveillance. In addition, mpMRI can be used for selection and monitoring of patients for active surveillance and treatment planning during surgery and focal therapy.

68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial.

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.

Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.

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.

Detection and localisation of primary prostate cancer using 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology.

OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.

Telemedicine Usage Among Urologists During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: Prior to the COVID-19 pandemic, urology was one of the specialties with the lowest rates of telemedicine and videoconferencing use. Common barriers to the implementation of telemedicine included a lack of technological literacy, concerns with reimbursement, and resistance to changes in the workplace. In response to the COVID-19 pandemic declared in March 2020, the delivery of urological services globally has quickly shifted to telemedicine to account for the mass clinical, procedural, and operative cancellations, inadequate personal protective equipment, and shortage of personnel. OBJECTIVE: The aim of this study was to investigate current telemedicine usage by urologists, urologists' perceptions on the necessity of in-person clinic appointments, the usability of telemedicine, and the current barriers to its implementation. METHODS: We conducted a global, cross-sectional, web-based survey to investigate the use of telemedicine before and after the COVID-19 pandemic. Urologists' perceived usability of telemedicine was assessed using a modified Delphi approach to create questions based on a modified version of the validated Telehealth Usability Questionnaire (TUQ). For the purposes of this study, telemedicine was defined as video calls only. RESULTS: A total of 620 urologists from 58 different countries and 6 continents participated in the survey. Prior to COVID-19, 15.8% (n=98) of urologists surveyed were using telemedicine in their clinical practices; during the pandemic, that proportion increased to 46.1% (n=283). Of the urologists without telemedicine experience, interest in telemedicine usage increased from 43.7% (n=139) to 80.8% (n=257) during the COVID-19 pandemic. Among urologists that used telemedicine during the pandemic, 80.9% (n=244) were interested in continuing to use it in their practice. The three most commonly used platforms were Zoom, Doxy.me, and Epic, and the top three barriers to implementing telemedicine were patients' lack of technological comprehension, patients' lack of access to the required technology, and reimbursement concerns. CONCLUSIONS: This is the first study to quantify the use, usability, and pervading interest in telemedicine among urologists during the COVID-19 pandemic. In the face of this pandemic, urologists' usage of telemedicine nearly tripled, demonstrating their ability to adopt and adapt telemedicine into their practices, but barriers involving the technology itself are still preventing many from utilizing it despite increasing interest.

Establishing a cryopreservation protocol for patient-derived xenografts of prostate cancer.

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 practicality of maintaining PDX models. Cryopreservation may also increase the accessibility of these important resources and provide new opportunities for preclinical studies on a broader spectrum of prostate tumors.

Multicentre evaluation of magnetic resonance imaging supported transperineal prostate biopsy in biopsy-naïve men with suspicion of prostate cancer.

OBJECTIVES: To analyse the detection rates of primary magnetic resonance imaging (MRI)-fusion transperineal prostate biopsy using combined targeted and systematic core distribution in three tertiary referral centres. PATIENTS AND METHODS: In this multicentre, prospective outcome study, 807 consecutive biopsy-naïve patients underwent MRI-guided transperineal prostate biopsy, as the first diagnostic intervention, between 10/2012 and 05/2016. MRI was reported following the Prostate Imaging-Reporting and Data System (PI-RADS) criteria. In all, 236 patients had 18-24 systematic transperineal biopsies only, and 571 patients underwent additional targeted biopsies either by MRI-fusion or cognitive targeting if PI-RADS ≥3 lesions were present. Detection rates for any and Gleason score 7-10 cancer in targeted and overall biopsy were calculated and predictive values were calculated for different PI-RADS and PSA density (PSAD) groups. RESULTS: Cancer was detected in 68% of the patients (546/807) and Gleason score 7-10 cancer in 49% (392/807). The negative predictive value of 236 PI-RADS 1-2 MRI in combination with PSAD of <0.1 ng/mL/mL for Gleason score 7-10 was 0.91 (95% confidence interval ± 0.07, 8% of study population). In 418 patients with PI-RADS 4-5 lesions using targeted plus systematic biopsies, the cancer detection rate of Gleason score 7-10 was significantly higher at 71% vs 59% and 61% with either approach alone (P < 0.001). For 153 PI-RADS 3 lesions, the detection rate was 31% with no significant difference to systematic biopsies with 27% (P > 0.05). Limitations include variability of multiparametric MRI (mpMRI) reading and Gleason grading. CONCLUSION: MRI-based transperineal biopsy performed at high-volume tertiary care centres with a significant experience of prostate mpMRI and image-guided targeted biopsies yielded high detection rates of Gleason score 7-10 cancer. Prostate biopsies may not be needed for men with low PSAD and an unsuspicious MRI. In patients with high probability lesions, combined targeted and systematic biopsies are recommended.

Zero hospital admissions for infection after 577 transperineal prostate biopsies using single-dose cephazolin prophylaxis.

PURPOSE: To determine the rate of hospital admissions for infection after transperineal biopsy of prostate (TPB) with single-dose cephazolin prophylaxis using a prospective database. METHOD: Between April 2013 and February 2016, 577 patients undergoing TPB had 2 g of cephazolin given intravenously at induction of anaesthesia. Data collected from these patients included age, PSA, prostate volume, number of cores taken and post-operative complications. RESULTS: No patients were readmitted to hospital with infection post-TPB. Seven patients developed acute urinary retention, and one patient developed clinical prostatitis that was treated with oral antibiotics in the community. CONCLUSION: It is safe to use single-dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports Australia's current Therapeutic Guidelines recommendation for TPB prophylaxis and the existing evidence that sepsis post-TPB is a rare complication. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study.

The state of TRUS biopsy sepsis: readmissions to Victorian hospitals with TRUS biopsy-related infection over 5 years.

OBJECTIVES: To describe the incidence, morbidity and mortality of men who developed infectious complications requiring hospital admission following TRUS prostate biopsy in Victoria, Australia. Further it aimed to report the financial cost of these admissions. SUBJECTS & METHODS: The Department of Health's Victorian Admitted Episodes Data Set was used to identify those patients who underwent TRUS biopsy in Victoria who were subsequently readmitted within 7 days to any Victorian hospital with infective complications from July 2007 to June 2012. All Victorian public and private hospitals were included. Patients were excluded if their biopsy was performed during a multi-day admission. Financial costing data was obtained where available from the Department Of Health and Human Services for readmissions with post-TRUS infection where available and adjusted to 2012 prices. Institutional ethics committee approval was granted for this study. RESULTS: Thirty-four thousand eight hundred and sixty-five TRUS biopsies were performed in the 5-year period. 1276 (3.66%) were readmitted to a Victorian hospital within 7 days. 604 (1.73%) of these were readmitted with a biopsy-related infection. No significant trend in sepsis rates was seen in 5 years. The median readmission LOS was 4 days. The total burden of readmissions was 3 686 days over 5 years. One patient readmitted with a biopsy related infection died during that episode of care. 20 051 (57.51%) of biopsies resulted in a diagnosis of prostate cancer. Financial costing data was available for 218 (36%) of infectious readmissions with a mean cost per readmission were $7 362 AUD (£4137 or $6844 USD, 95% CI $6219-8505 AUD) or $1 256 AUD per day. CONCLUSION: Infection following TRUS biopsy was associated with a readmission rate for infection of 1 in 57 biopsies, an excess of 3 686 bed days required over 5 years with a cost of $1 256 AUD per day. The rate of infection remained stable for the period examined.

Transperineal biopsy prostate cancer detection in first biopsy and repeat biopsy after negative transrectal ultrasound-guided biopsy: the Victorian Transperineal Biopsy Collaboration experience.

OBJECTIVES: To present the Victorian Transperineal Biopsy Collaboration (VTBC) experience in patients with no prior prostate cancer diagnosis, assessing the cancer detection rate, pathological outcomes and anatomical distribution of cancer within the prostate. PATIENTS AND METHODS: VTBC was established through partnership between urologists performing transperineal biopsies of the prostate (TPB) at three institutions in Melbourne. Consecutive patients who had TPB, as first biopsy or repeat biopsy after previous negative transrectal ultrasound-guided (TRUS) biopsy, between September 2009 and September 2013 in the VTBC database were included. Data for each patient were collected prospectively (except for TPB before 2011 in one institution), based on the minimum dataset published by the Ginsburg Study Group. Univariate and multivariate analyses were used to identify factors predictive of cancer detection on TPB. RESULTS: In all, 160 patients were included in the study, of whom 57 had TPB as first biopsy and 103 had TPB as repeat biopsy after previous negative TRUS biopsies. The median patient age at TPB was 63 years, with the repeat-biopsy patients having a higher median serum PSA level (5.8 ng/mL for first biopsy and 9.6 ng/mL for repeat biopsy) and larger prostate volumes (40 mL for first biopsy, and 51 mL for repeat biopsy). Prostate cancer was detected in 53% of first-biopsy patients and 36% of repeat-biopsy patients, of which 87% and 81%, respectively, were clinically significant cancers, defined as a Gleason score of ≥7, or more than three positive cores of Gleason 6. Of the cancers detected in repeat biopsies, 75% involved the anterior region (based on the Ginsburg Study Group's recommended biopsy map), while 25% were confined exclusively within the anterior region; a lower proportion of only 5% of cancers detected in first biopsies were confined exclusively within the anterior region. Age, serum PSA level and prostate volume were predictive of cancer detection in repeat biopsies, while only age was predictive in first biopsies. CONCLUSIONS: TPB is an alternative approach to TRUS biopsy of the prostate, offering a high rate of detection of clinically significant prostate cancer. It provides excellent sampling of the anterior region of the prostate, which is often under-sampled using the TRUS approach, and should be considered as an option for all men in whom a prostate biopsy is indicated.

Patients with medical risk factors for chronic kidney disease are at increased risk of renal impairment despite the use of nephron-sparing surgery.

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 (R(2) = 0.37) and new-onset eGFR <45 mL/min (R(2) = 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.

Risk factors for infection following prostate biopsy - a case control study.

BACKGROUND: Infection is a complication of TRUS prostate biopsy, despite the use of antimicrobial prophylaxis. Worryingly the rate of infectious complications following TRUS biopsy has been shown to be increasing. We aimed to determine the rate, severity, risk factors, standard patterns of care and microbiology resistance profiles associated with TRUS biopsy sepsis. METHODS: A retrospective case-control study was conducted. Using electronic coding all patients who presented to Cabrini Hospital with sepsis following a TRUS biopsy from 2009 to 2013 were identified. Validated cases were matched to controls in a ratio of 1:3. Eligible controls were required to have undergone a TRUS biopsy at the same surgical institution as the case and in the closest period of time. Demographic, procedural and patient related data-points were recorded for all patients using hospital and urologist records. Univariate logistic regression models were constructed and used to determine risk factors associated with infection. RESULTS: 71 cases developed sepsis following TRUS biopsy and were matched to 213 controls. The average rate of sepsis over the 5-year study period was 1.5 %. A SOFA score ≥ 2 was identified in 28 % of cases. We found a high prevalence of antimicrobial resistant E. coli, with 61 % of blood culture isolates classified as Multidrug resistant organisms. Eight different prophylactic antimicrobial regimens were identified with 33 % of cases receiving ineffective antimicrobial prophylaxis. Statistically significant risk factors included previous antimicrobial use and prior international travel within the six months prior to biopsy. CONCLUSIONS: TRUS biopsy is an elective procedure and as such needs to be associated with minimal morbidity. The patterns of care surrounding periprocedural variables for TRUS biopsies were non-uniform and diverse. A wide variety of different prophylaxis regimens and bowel preparation routines were recorded. Patients with risk factors for sepsis may represent a better target population for intervention with alternative preventative strategies. Alternative preventative options include augmented prophylaxis, tailored prophylaxis or the TP biopsy approach either as a first line biopsy modality or based on epidemiological risk factors.