Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. METHODS: Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.

What is the best way to manage ureteric calculi in the time of COVID-19? A comparison of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy (URS) in an Australian health-care setting.

Objectives: To determine the best way to intervene for ureteric stones which still require treatment during the COVID-19 pandemic, with respect to infection control. In this setting, in which resources are constrained, extracorporeal shockwave lithotripsy (SWL) has prima facie advantages over ureteroscopy (URS). It is also necessary to also consider posttreatment resource consumption in regards to complications and repeat procedures. Subjects and methods: The ideal ureteric stone treatment during a pandemic such as COVID-19 would involve minimum resource consumption and a minimum number of patient attendances. We compared all patients initially treated with SWL to those initially treated with URS for acute ureteral colic within the state of Victoria, Australia in 2017. Results: A total of 2724 ureteric stones were analyzed, a cumulative "3-month exposure and burden on the healthcare system" was calculated for each patient by their initial procedure type. The readmission rate for URS was significantly higher than for SWL, 0.92 readmissions/patient for URS versus 0.54 readmissions/patient for SWL (P < .001). The cumulative hospital stay per patient for these two procedures was 2.35 days for SWL versus 3.21 days for URS (P < .001). The number of procedures per patient was 1.52 for SWL versus 1.89 for URS (P = .0213). Conclusions: Patients with ureteric stones treated initially by SWL have shorter length of stay with fewer overall attendances and procedures at 3 months than those treated with URS. During a pandemic such as COVID-19, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS.

Which has more complications?-Shockwave lithotripsy versus endoscopic treatment of renal calculi with 1-year follow-up in an Australian population.

Introduction and objectives: Renal calculi are a common medical problem with incidence rates calculated to be approximately 6%-9% in men & 3%-4% in women worldwide. Incidence appears to be increasing. This study compares emergency presentations and unplanned readmissions between extracorporeal shock wave lithotripsy (SWL) and pyeloscopic stone treatment in the population of Victoria, Australia after 1-year follow-up. Methods: This is a population study comparing all patients with renal calculi electively treated with SWL to those initially treated with flexible ureteroscopy (URS) in Victoria, Australia. We used data linkage across the state of Victoria to follow patients treated with either modality in a 12 months period (with no urological surgery in the prior 12 months). Each patient's emergency presentations and subsequent re-admissions were followed up for 1 year after their index treatment to assess for stone complications. We assessed for selection bias between the two patient groups by comparing age, gender, insurance status, geographical location, and comorbidity scores. Results: We report stone-related complications for 739 flexible URS and 1317 SWL procedures undertaken across public and private hospitals in Victoria over 12 months. Unplanned emergency presentations within 60-days of surgery were (22/739) 2.98% for flexible URS patients and (83/1317) 6.30% for SWL patients (P = .001); however, at 12 months, this became 16.23% (120/739) for flexible URS patients and 12.83% (169/1317) for SWL patients (P = .034). Flexible URS patients were more likely than SWL patients to be admitted with 71.76% of flexible URS versus 53.97% of SWL patients requiring an admission at any given emergency presentation (P ≤ .001) within 12 months. On multivariate analysis, both flexible URS ([OR] 1.67, CI 1.23-2.26, P = .001) and being a public patient ([OR] 3.06, CI 2.24-4.18, P < .001) significantly increased the likelihood that patients required an unplanned re-admission within 12 months. Conclusions: There is work needed to reduce emergency presentations and unplanned re-admissions after both SWL and flexible URS. At 12-months follow-up, unplanned emergency visits and re-admission rates were significantly more after flexible URS. Symptoms at emergency presentation indicate that better education regarding stent management is needed, especially in the public health care system.

Hospital volume and perioperative outcomes for radical cystectomy: a population study.

OBJECTIVES: To evaluate the association between hospital volume and perioperative outcomes of radical cystectomy (RC) using state population data for a contemporary Australian cohort. PATIENTS AND METHODS: Patients undergoing RC for urothelial malignancy in the state of Victoria, Australia between July 2003 and June 2014 were identified using the Victorian Admitted Episodes Dataset (VAED). Hospitals were divided into tertiles according to their caseload per year. Hospitals performing <4 RCs/year were defined as low-volume hospitals (LVH), 4-10 RCs/year as medium-volume hospitals (MVH), and >10 RCs/year as high-volume hospitals (HVH). Perioperative outcomes derived included: in-hospital mortality (IHM), prolonged length of stay (LOS; >14 days), prolonged intensive care unit (ICU) admission (>24 h), and requirement for blood transfusion. The relationship between hospital volume and perioperative outcomes was assessed using logistic regression. RESULTS: During the 11-year study period, 803 patients underwent RC for bladder cancer. The overall IHM rate was 2.2% (LVH 3.7%, MVH 2.5%, HVH 0.9%). Other outcomes observed were prolonged LOS (45%), prolonged ICU admission (31%) and requirement for blood transfusion (56%). On multivariate analysis, LVH was found to be associated with increased IHM (odds ratio [OR] 5.74, P = 0.04) and prolonged ICU admission (OR 11.58, P < 0.001) when compared to HVH. There was a lower rate of prolonged LOS for LVH (OR 0.60, P = 0.01). No significant relationship was identified for LVH and blood transfusion. CONCLUSION: Perioperative outcomes in Victoria are comparable to international standards. Our results add further population study evidence to the volume-outcome relationship in RC. There was a significant association between LVH and both IHM and prolonged ICU admission. This subgroup of patients would appear to benefit from transfer of care to a HVH. The role of centralisation of RC in Australia should be further considered.

The danger of chlorhexidine in lignocaine gel: A case report of anaphylaxis during urinary catheterisation.

This article describes a case of anaphylaxis secondary to chlorhexidine during urethral catheterisation. Despite little evidence for the use of antiseptic lubricants in preventing catheter-associated urinary tract infections, the distribution and use of such products continues to be widespread. Chlorhexidine-free lubricating gel is widely available and should be used for urological procedures wherever possible.

Dichotomous estimation of prostate volume: a diagnostic study of the accuracy of the digital rectal examination.

PURPOSE: To assess the diagnostic reliability of a dichotomous digital rectal examination (DRE) tool in assessing prostate volume (PV) compared to gold-standard transrectal ultrasound (TRUS) volume measurement. MATERIALS AND METHODS: Male patients presenting to a single tertiary referral centre urology practice requiring TRUS were prospectively recruited between January 2010 and August 2011. Size was estimated by DRE immediately prior to TRUS measurement. DRE measurements were classed into four groups: <30 mL , 30 to 49 mL, 50 to 99 mL and >100 mL. The primary outcomes were sensitivity, specificity, and the positive and negative likelihood ratios for a 30 mL cut-off. RESULTS: Three hundred and three patients were recruited to the study. The median age of the study group was 64.9 years. On TRUS analysis, 244 patients had a PV larger than 30 mL and 139 of them, larger than 50 mL. The median PV was 47 mL with a median International Prostate Symptom Score of 10 and prostatic specific antigen (PSA) of 5.7. When analysed for the ability to identify a gland larger than 30 mL, DRE had a high sensitivity and low negative likelihood ratio. The median PSA level (ng/L) for prostates measured by DRE with a 30 mL cut-off was significantly different with higher median PSA values for volumes larger than 30 mL. CONCLUSIONS: DRE is a reliable tool for dichotomous assessment of prostatic volumes above 30 mL and 50 mL. These results illustrate the value of re-examining the role of categorical DRE estimations in benign prostatic hyperplasia patients.