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Objectives: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations., Patients and Methods: The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC., Results: A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2-macrophage (CD163) when comparing the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033)., Conclusion: Sub-urothelial injection of durvalumab is feasible and safe without immune-related AEs and shows local immunological effects., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To determine the effectiveness of technetium-99m ( 99m Tc)-sestamibi single-photon emission computerised tomography/computerised tomography (SPECT/CT) in distinguishing between malignant and benign renal lesions., Patients and Methods: Between June 2018 and October 2020 all patients with new indeterminate small renal masses (SRMs) underwent 99m Tc-sestamibi renal SPECT/CT before biopsy or surgery. The accuracy of 99m Tc-sestamibi imaging diagnoses was assessed against histopathology. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off for the tumour:normal uptake ratio. Logistic regression was used to determine if quantitative analysis significantly added to visual interpretation alone., Results: A total of 74 patients with SRMs were investigated with 99m Tc-sestamibi SPECT/CT. The SPECT/CT correctly identified 49 malignant tumours and 11 benign tumours, resulting in a sensitivity of 0.89 (95% confidence interval [CI] 0.77-0.95) and a specificity of 0.73 (95% CI 0.45-0.91). The ROC analysis of uptake ratios demonstrated that a tumour:normal uptake ratio of 0.41 provided optimal diagnostic accuracy (sensitivity 0.81, specificity 0.88, area under the curve 0.883 [95% CI 0.794-0.971]). The uptake ratio was also highly significant in excluding malignancy on univariate logistic regression analysis whereby the higher the uptake ratio, the lower the chances were for malignancy (odds ratio 0.009, 95% CI 0.001-0.118, P < 0.001). However, this did not improve diagnostic accuracy when compared to visual interpretation alone., Conclusion: 99m Tc-sestamibi SPECT/CT is a non-invasive technique with good accuracy in determining if a SRM is benign or malignant., (© 2022 BJU International.)

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., (© 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: This article presents the clinical trial protocol for a phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (NMIBC), the SUB-urothelial DUrvalumab injection-1 study (SUBDUE-1). The primary objectives of this study are to assess the safety of sub-urothelial injection of durvalumab using patient reported outcome measures and observed local or systemic adverse events. The secondary objectives are to examine the local immunological efficacy of sub-urothelial administration of durvalumab., Patients and Methods: The SUBDUE-1 trial will include adult patients with either high-risk NMIBC or MIBC, who are scheduled for radical cystectomy or who have refused or are unsuitable for systemic neoadjuvant chemotherapy. Three fixed total dose levels of durvalumab (25, 75, 150 mg) will be studied to identify a dose suitable to be taken forward into phase II trials. The primary endpoint is to evaluate the safety and tolerability of the trial intervention in terms of the incidence and severity of adverse events and the potential establishment of dose-limiting toxicities. The secondary efficacy endpoints include rates of pT0 status at resection, lymph node status, as well as the change in distribution of tumour-infiltrating lymphocytes and tumour-activated macrophages between pre- and post-injection bladder biopsies. Translational studies will focus on bladder tumour molecular sub-typing, immune infiltrate characterisation, and immune checkpoint protein expression relative to efficacy end-points., Outcome and Significance: If proven safe and effective, this novel strategy comprising sub-urothelial durvalumab injections aimed at promoting an anti-tumour immune reaction, will provide additional treatment options for reducing tumour recurrence and progression in treatment-naïve patients with high-risk NMIBC or in patients with bacille Calmette-Guérin-refractory NMIBC. Local administration of durvalumab may be associated with a reduced rate of immunological side-effects and lower costs when compared to systemic delivery., (© 2021 The Authors. BJU International © 2021 BJU International.)

Objectives: To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen-deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft-tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM)., Patients and Methods: In all, 104 patients with prostate cancer, aged 48-84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X-ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months., Results: There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (-0.4% vs -1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (-1.4% to -2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12-month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively)., Conclusions: Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment-related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT., (© 2018 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To quantify and examine the causes of delays in the diagnosis and initial treatment of patients with bladder cancer in Western Australia., Subjects and Methods: All attendances at a one-stop haematuria clinic at a public tertiary-level hospital in Western Australia between May 2008 and April 2014 were reviewed retrospectively. All patients diagnosed with a bladder tumour over this period were identified. These patients and their general practitioners were contacted retrospectively and invited to participate in telephone interviews, with additional data collected from clinical records as required. Waiting times to presentation, referral, assessment, and initial treatment were established for patients who presented with visible haematuria., Results: Of 1 365 attendances, 151 patients were diagnosed with a bladder tumour and 100 of these were both suitable and agreed to participate in the study. For patients with visible haematuria the median (range) waiting time from initial bleeding to surgery was 69.5 (9-1 165) days. This was comprised of a median (range) pre-referral waiting time of 12 (0-1 137) days, assessment waiting time of 23.5 (0-207) days, and treatment waiting time of 20 (1-69) days. Reasons for prolonged waiting times included poor public awareness, patient fear and anxiety, delayed and non-referral from primary care, administrative delays, and resource limitations., Conclusion: Many patients experience significant delays in the diagnosis and treatment of their bladder cancer in Western Australia, and this probably reflects national trends. These concerning data warrant consideration of how delays can be reduced to improve outcomes for these patients., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer., Patients and Methods: Men who had completed treatment for low- to moderate-risk prostate cancer within the previous 8 weeks were eligible. Participants were randomized to usual care or shared care. Shared care entailed substituting two hospital visits with three visits in primary care, a survivorship care plan, recall and reminders, and screening for distress and unmet needs. Outcome measures included psychological distress, prostate cancer-specific quality of life, satisfaction and preferences for care and healthcare resource use., Results: A total of 88 men were randomized (shared care n = 45; usual care n = 43). There were no clinically important or statistically significant differences between groups with regard to distress, prostate cancer-specific quality of life or satisfaction with care. At the end of the trial, men in the intervention group were significantly more likely to prefer a shared care model to hospital follow-up than those in the control group (intervention 63% vs control 24%; P<0.001). There was high compliance with prostate-specific antigen monitoring in both groups. The shared care model was cheaper than usual care (shared care AUS$1411; usual care AUS$1728; difference AUS$323 [plausible range AUS$91-554])., Conclusion: Well-structured shared care for men with low- to moderate-risk prostate cancer is feasible and appears to produce clinically similar outcomes to those of standard care, at a lower cost., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To report on the structure and outcomes of a new 'One Stop' Prostate Clinic (OSPC) designed specifically for rural and remote men., Patients and Methods: Prospective cohort study of the first 200 rural or remote men to access a new OSPC at a public tertiary-level hospital in Western Australia between August 2011 and August 2014. Men attended for urological assessment, and proceeded to same-day transrectal ultrasonography-guided prostate biopsies, if appropriate. Referral criteria were either two abnormal age-related prostate-specific antigen (PSA) levels in the absence of urinary tract infection (UTI), or an abnormal digital rectal examination (DRE) regardless of PSA level., Results: The median (range) distance travelled was 1545 (56-3229) km and median (range) time from referral to assessment was 33 (2-165) days. The median (range) age was 62 (38-85) years, PSA level was 6.7 (0.5-360) ng/mL and 39% (78/200) had a suspicious DRE. In all, 92% (184/200) of men proceeded to prostate biopsies, and 60% (111/184) of these men were diagnosed with prostate cancer. Our complication rate was 3.5% (6/172). Radical prostatectomy (46/111), active surveillance (28/111) and external beam radiation therapy (26/111) were the commonest subsequent treatment methods. A $1045 (Australian dollars) cost-saving per person was estimated based on the reduced need for travel with the OSPC model., Conclusion: The OSPC is an effective and efficient model for assessing men suspected of having prostate cancer living in rural and remote areas of Western Australia, and this model may be applicable to other areas., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To quantify the outcomes of retrograde ureteric stenting in the setting of infected hydronephrosis secondary to ureteric calculi., Patients and Methods: Prospective analysis of all patients over a 15-month period admitted with infected obstructed kidneys secondary to ureteric calculi. Inclusion criteria were based on clinical evidence of systemic inflammatory response syndrome (SIRS) and radiological evidence of obstructing ureteric calculi. Outcome measures included success of procedure, admission to intensive care unit (ICU), length of hospital stay, morbidity, and all-cause mortality during hospital admission., Results: In all, 52 patients were included. Success of retrograde ureteric stenting was 98%. In all, 17% of patients required an ICU admission, with a post ureteric instrumentation ICU admissions rate of 6%. The mean white cell count and serum creatinine improved significantly after the procedure. Major complication rate included septic shock 6%, but there were no episodes of major haemorrhage and no deaths., Conclusion: Retrograde ureteric stenting is safe and effective in infected obstructed kidneys with results comparable to percutaneous nephrostomy tube insertion. Post instrumentation ICU admissions occur in 6% of retrograde stentings., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To examine whether or not the combination of diclofenac suppository with peri-prostatic nerve block (PPNB) was effective in reducing the degree of pain experienced during transrectal ultrasound (TRUS)-guided prostate biopsy in a randomised single-blind placebo-controlled trial., Patients and Methods: In all, 96 patients having a planned TRUS-guided prostate biopsy were randomised into one of the following arms on a 1:1 basis: 10 mL 1% lignocaine PPNB and placebo suppository (control) or 10 mL 1% lignocaine PPNB and 100 mg diclofenac suppository (treatment). Pain scores were recorded using the Numerical Rating Scale for pain (0-10) at the following time-points: (i) introduction of probe, (ii) during biopsy, (iii) 1 h after biopsy, (iv) later that evening (≈6 h after biopsy) and (v) 1 day after biopsy. Patients were asked about their preferred method for pain control if a repeat TRUS-guided prostate biopsy was required: local anaesthetic (LA) again or intravenous sedation., Results: There were no significant differences in age (P = 0.653) or PSA level (P = 0.584) between either study arm. The differences in pain scores between the control and treatment groups were not significant at Time 1 (probe insertion; P = 0.299), Time 2 (biopsy; P = 0.983), Time 4 (evening after; P = 0.231) and Time 5 (1 day after biopsy; P = 0.384). At Time 3 (1 h after biopsy), the control pain scale scores were statistically significantly higher than the treatment pain scale scores (P = 0.044). There was no difference between treatment (87%) and control (80%) groups as to whether they would prefer to repeat the biopsy under LA (P = 0.373)., Conclusion: The use of a diclofenac suppository with PPNB did not show any clinically meaningful effect in decreasing pain or improving tolerability of TRUS-guided prostate biopsy and is not recommended. PPNB TRUS-guided biopsy is extremely well tolerated, with >80% of patients electing for subsequent LA biopsy if required., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To review the literature and make practical recommendations regarding the conservative management of renal trauma., Patients and Methods: Relevant articles and guidelines published between 1980 and 2014 were reviewed. Graded recommendations were constructed by a multi-disciplinary panel consisting of urologists, radiologists, and infectious disease physicians. These recommendations underwent formal review and debate at the Western Australian USANZ 2013 state conference, and were presented at the USANZ 2014 annual scientific meeting., Results: The literature on the conservative management of renal trauma is reviewed within the framework of the American Association for the Surgery of Trauma (AAST) kidney injury severity scale. Graded recommendations are made regarding several key topics including: imaging, inpatient management, antibiotics, return to activity, and follow-up. Grade IV injuries and intraoperative consults are examined separately in view of the difficulties these groups cause in making appropriate treatment decisions., Conclusion: A practical clinical guideline is provided regarding the conservative management of renal trauma., (© 2014 The Authors. BJU International © 2014 BJU International.)

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate. We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone., Objective: To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guérin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC)., Methods: We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone. Studies that did not use maintenance BCG were excluded. The meta-analysis was performed using the fixed effects model., Results: Four trials were identified, including 801 patients. Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79-1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61-1.27; P = 0.5). The risk of recurrence (RR 0.75; 95% CI 0.61-0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25-0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded. Toxicity was similar for both groups., Conclusions: Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence. Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone., (© 2012 BJU International.)

• Intravesical therapy is a well-established treatment option for non-muscle-invasive bladder cancer (NMIBC). • Choosing the appropriate intravesical agent, schedule and duration of treatment has long been an area of debate. • We review the intravesical agents that are currently used in the management of NMIBC and examine the indications and limitations of their use. • Given the relative high rates of toxicity, failure and non-completion of traditional treatments we also examine some of the newer treatment options available., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? Haematuria is a symptom of urologic cancer particularly bladder cancer and timely diagnosis can prevent disease from progression to a more advanced or incurable stage. The 'One Stop' Haematuria clinic is the first rapid assessment clinic for haematuria in a public hospital in Western Australia. The results from this study have confirmed that it is an efficient and effective model in the streamlined care of patients with haematuria and provides evidence to support a more widespread adoption of this model of care., Objective: • To report the prospective outcomes and clinic process for the first 500 patients at a new 'one stop' Haematuria Clinic (OSHC) in a Western Australian public hospital., Patients and Methods: • The first 500 patients who attended the weekly OSHC between May 2008 and February 2011 were included in this paper. • Patients with haematuria were referred by various specialties. Gender, age, outcomes following OSHC attendance, diagnoses and wait times were recorded., Results: • In all, 311 males and 189 females presented to the clinic with visible haematuria (296 cases) and microscopic haematuria (204 cases). • Sixty-six new cancers (13.2%) were diagnosed, 63 urological and three non-urological. •  Fifty-one patients (10.2%) were diagnosed with transitional cell carcinoma of the bladder. Further breakdown of staging for bladder transitional cell carcinoma diagnoses were stage Ta (23 patients), stage T1 (21 patients) and stage 2-4 (seven patients). • Sixty-nine patients (13.8%) were diagnosed with urological pathologies requiring surgery. Thirty-four patients (6.8%) were followed up by the nurse practitioner or continence advisors. In all, 61.2% of patients were discharged after a single visit to the OSHC. •  Excluding those requiring surgery only 3.4% patients required further urologist follow-up., Conclusion: •  The results have demonstrated that the first OSHC in a public Western Australian hospital is an efficient and effective model for the streamlined care of patients with haematuria. •  We encourage that similar models are adopted in other public hospitals in the region., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To measure expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the prostates of men after transurethral resection of the prostate (TURP) following 2 weeks of treatment with finasteride., Patients and Methods: Sixty-four men scheduled to undergo TURP were randomized to receive 5 mg of finasteride or placebo daily for 2 weeks before surgery. Sections of prostatic urothelium were stained for VEGF expression and for CD31 to assess MVD. Ten consecutive, non-overlapping high-power fields were analysed in a blinded fashion., Results: In all, 31 men received finasteride and 33 placebo; the groups were similar in patient age, resected prostate weight, preoperative catheterization, prostate-specific antigen level, aspirin use, spinal anaesthesia and postoperative diagnosis of prostate cancer. The mean (95% confidence interval) MVD was significantly lower in the finasteride group (60, 55-65) than in the placebo group (71, 64-78; P < 0.01). Similarly, the mean expression of VEGF was significantly lower in the finasteride group (47, 43-52 vs 61, 54-67; P < 0.001), Conclusion: Finasteride inhibits angiogenic growth factors leading to reduced vascularity, and this is the basis of its action in reducing haematuria of prostatic origin. The present study shows that finasteride influences the prostatic microvasculature after only 2 weeks exposure.