The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer.

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.

'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.

Bladder infusion versus standard catheter removal for trial of void: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy and time-to-discharge of two methods of trial of void (TOV): bladder infusion versus standard catheter removal. METHODS: Electronic searches for randomized controlled trials (RCTs) comparing bladder infusion versus standard catheter removal were performed using multiple electronic databases from dates of inception to June 2020. Participants underwent TOV after acute urinary retention or postoperatively after intraoperative indwelling catheter (IDC) placement. Quality assessment and meta-analyses were performed, with odds ratio and mean time difference used as the outcome measures. RESULTS: Eight studies, comprising 977 patients, were included in the final analysis. Pooled meta-analysis demonstrated that successful TOV was significantly higher in the bladder infusion group compared to standard TOV (OR 2.41, 95% CI 1.53-3.8, p = 0.0005), without significant heterogeneity (I2=19%). The bladder infusion group had a significantly shorter time-to-decision in comparison to standard TOV (weighted mean difference (WMD)-148.96 min, 95% CI - 242.29, - 55.63, p = 0.002) and shorter time-to-discharge (WMD - 89.68 min, 95% CI - 160.55, - 18.88, p = 0.01). There was no significant difference in complication rates between the two groups. CONCLUSION: The bladder infusion technique of TOV may be associated with a significantly increased likelihood of successful TOV and reduced time to discharge compared to standard TOV practices.

A prospective, matched comparison of ultra-low and standard-dose computed tomography for assessment of renal colic.

OBJECTIVE: To determine the diagnostic accuracy of ultra-low-dose computed tomography (ULDCT) compared with standard-dose CT (SDCT) in the evaluation of patients with clinically suspected renal colic, in addition to secondary features (hydroureteronephrosis, perinephric stranding) and additional pathological entities (renal masses). PATIENTS AND METHODS: A prospective, comparative cohort study was conducted amongst patients presenting to the emergency department with signs and symptoms suggestive of renal or ureteric colic. Patients underwent both SDCT and ULDCT. Single-blinded review of the image sets was performed independently by three board-certified radiologists. RESULTS: Among 21 patients, the effective radiation dose was lower for ULDCT [mean (SD) 1.02 (0.16) mSv] than SDCT [mean (SD) 4.97 (2.02) mSv]. Renal and/or ureteric calculi were detected in 57.1% (12/21) of patients. There were no significant differences in calculus detection and size estimation between ULDCT and SDCT. A higher concordance was observed for ureteric calculi (75%) than renal calculi (38%), mostly due to greater detection of calculi of <3 mm by SDCT. Clinically significant calculi (≥3 mm) were detected by ULDCT with high specificity (97.6%) and sensitivity (100%) compared to overall detection (specificity 91.2%, sensitivity 58.8%). ULDCT and SDCT were highly concordant for detection of secondary features, while ULDCT detected less renal cysts of <2 cm. Inter-observer agreement for the ureteric calculi detection was 93.9% for SDCT and 87.8% for ULDCT. CONCLUSION: ULDCT performed similarly to SDCT for calculus detection and size estimation with reduced radiation exposure. Based on this and other studies, ULDCT should be considered as the first-line modality for evaluation of renal colic in routine practice.

Delays in the diagnosis and initial treatment of bladder cancer in Western Australia.

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.

BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301).

BACKGROUND: Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. METHODS AND DESIGN: The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000513718 ).

A 'One Stop' Prostate Clinic for rural and remote men: a report on the first 200 patients.

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.

The conservative management of renal trauma: a literature review and practical clinical guideline from Australia and New Zealand.

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.

Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of 18F-fluorodeoxyglucose positron (18F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy. Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and 18F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases. FDG-PET definitions for positive sites were assessed depending on SUV Max (nodes with SUVmax >4 at any size, SUV > 2 for lymph nodes >8 mm, or any SUV if the lymph node was >10 mm on axial images). For CT scanning, enlarged LN by RECIST 1.1 criteria (>10 mm) as well as qualitative findings suggesting metastasis were considered positive. The analysis was based on the comparison of CT and 18F-FDG-PET findings to histopathology results from LN dissection or biopsies. Results: Sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV) of CT versus FDG-PET for detecting metastasis, in patients who underwent pelvic LN dissection or biopsy of lesions suspicious of metastases, were 46.6% (95% CI: 21%-70%) versus 60% (95% CI: 32%-84%), 100% (95% CI: 91%-100%) versus 83.78% (95% CI: 69%-94%), 100% (95% CI: 63%-100%) versus 60% (95% CI: 32%-84%), and 82.2% (95% CI: 68%-92%) versus 83.78% (95% CI: 69%-94%), respectively. 7/75 (9.3%) patients avoided cystectomy due to 18F-FDG-PET features of metastases that were not detected by CT. Conclusion: FDG-PET may be more sensitive than CT for metastases in the staging of bladder cancer, which resulted in significant avoidance of aggressive local management in cases with occult metastasis.

Torsion of an intra-abdominal testis presenting as acute abdominal pain - A rare diagnosis.

Cryptorchidism is associated with a higher risk of malignancy, infertility, and torsion. Torsion of an intra-abdominal testis is a rare cause of acute abdominal pain in the post-pubertal male but must be considered in men presenting with abdominal pain and a history of cryptorchidism. We present an unusual case of a patient with acute abdominal pain found to have torsion of a left intra-abdominal testis and his management.

Centralization and prospective audit of cystectomy are necessary: a commentary on the case for centralization, supported by a contemporary series utilizing the ANZUP cystectomy database.

Bladder cancer (BC) outcomes are unacceptably poor. In Australia, BC survival is actually deteriorating. There is an urgent need to improve outcomes in BC patients, which requires a multipronged approach. One area deserving closer scrutiny is radical cystectomy. Audit is necessary to identify areas for improvement and without it, outcomes remain unknown. Evidence convincingly shows high-volume surgeons and centers improve cystectomy outcomes including overall survival, yet centralization has still not occurred. The Australia and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group cystectomy database has been established to facilitate cystectomy audit in Australia and New Zealand. We present initial data from the ANZUP cystectomy database from a single high-volume center, discuss the benefits of centralization and its challenges in the Asia-Pacific context.

Lymph node assessment technique matters in radical cystectomy for bladder cancer.

BACKGROUND: For patients undergoing radical cystectomy with pelvic lymph node dissection for urothelial cancer, a lymph node count of at least 16 is associated with improved cancer-specific and overall survival. Lymph node yield is presumed to relate directly to extent of dissection and surgical quality, however limited studies have reviewed the impact of the pathological assessment process of lymph nodes on lymph node yield. METHOD: A retrospective assessment of 139 patients who had radical cystectomy for urothelial cancer between March 2015 and July 2021 from Fiona Stanley Hospital (Perth, Australia) by a single surgeon was assessed. A change in pathological assessment process from assessment of only palpable lymph nodes to microscopic assessment of the entire submitted specimens occurred in August 2018. Patients were divided into two groups accordingly and other relevant demographic and pathological data was recorded. The impact of pathological processing technique on lymph node yield was assessed using the Student T test and logistical regression was used to assess the impact of other demographic variables. RESULTS: The mean lymph node yield was 16.2 nodes (IQR 12-23) in 54 patients in the pre-process change group compared to 22.4 nodes (IQR 15-28.4) in 85 patients in the post-process change group (P < 0.0001). 53.7% had 16 or more nodes in the pre-process change group compared to 71.3% in the post-process change group (P = 0.04). Age, BMI, and gender were not significant predictors of lymph node yield. CONCLUSION: The current study demonstrates that the microscopic assessment of all lymph node tissue detects significantly more lymph nodes than only examining palpably abnormal tissue. Pathologic assessment protocols should be standardized to this technique to ensure the utility of lymph node yield as a quality metric.

Efficacy and Feasibility of Presurgical Exercise in Bladder Cancer Patients Scheduled for Open Radical Cystectomy.

PURPOSE: This study aimed to examine the feasibility and potential efficacy of presurgical exercise in patients with bladder cancer scheduled for open radical cystectomy with follow-up postsurgery. METHODS: Prospective single-group design with assessments at baseline, presurgery, and 3 months postsurgery was used in this study. Multimodal supervised resistance and aerobic exercise was undertaken 2-3 d·wk -1 at moderate intensity for a median of 3.5 wk (interquartile range [IQR] = 1.3-5.6). Feasibility was assessed by recruitment and completion rates, patient safety, program tolerance, adherence, and compliance. Lean and fat mass were assessed by dual-energy x-ray absorptiometry, physical function by a battery of tests (chest press and leg press strength, 6-min walk test [6MWT], timed up-and-go, repeated chair rise), and quality of life (QoL), psychological distress, and body image by questionnaire. Hospital length of stay (LOS) and complications were assessed by medical records. RESULTS: Thirty-seven patients were referred with 20 recruited (67.3 ± 12.2 yr) and a presurgery intervention completion rate of 80% (16 of 20). The individual median program adherence was 100.0% (IQR = 89.4-100.0) with compliance of 100.0% (IQR = 90.5-100.0) for resistance exercise and 81.8% (IQR = 55.0-99.5) for aerobic exercise. There were no exercise-related adverse events. Body composition did not change presurgery; however, there were improvements ( P < 0.05) in leg press strength (16%), 6MWT distance (8%), timed up-and-go (12%), chair rise (10%), and multiple QoL domains including mental health. Median LOS was 8.0 d (IQR = 7.0, 15.0). Postsurgery, there were declines in components of QoL and apparent body image dissatisfaction. CONCLUSIONS: A preradical cystectomy exercise program is feasible, safe, and well tolerated with improvements in physical function and QoL. Supervised multimodal exercise in bladder cancer patients before cystectomy can enhance physical and mental health potentially buffering the effects of surgery.

Spontaneous bleeding from an unusual renal mass: A case of gestational choriocarcinoma related to previous pregnancy over a decade earlier.

Gestational choriocarcinoma is an uncommon trophoblastic malignancy, occurring in females after pregnancy, which is rarely encountered by urologists. It can be rapidly progressive, however metastases to other organs can occur after a prolonged latency period. We describe a rare case of solitary metastatic gestational choriocarcinoma presenting with spontaneous bleeding from a renal mass, over a decade after the associated pregnancy with a presumed sub-clinical primary tumour. This case demonstrates the importance of recognising gestational choriocarcinoma as a potential differential diagnosis of spontaneous bleeding renal mass in females of child-bearing age as a urologist given the often-aggressive nature of the disease.

Transrectal prostate biopsy sepsis rate following reduced quinolone antibiotic prophylaxis from six doses to single dose.

BACKGROUND: This study aimed to evaluate the rates of infective complication related to transrectal prostate biopsy (TRPB) as our centre changed its protocol from six doses over 3 days to a single pre-procedure prophylactic dose. METHODS: This prospective cohort study identified infective complication in patients who attended and subsequently underwent TRPB at the time of their one-stop prostate clinic at our public tertiary hospital between August 2011 and April 2017. Patients who underwent TRPB between August 2011 and November 2014 received six doses of 500 mg of ciprofloxacin, taken twice daily over 3 days. This protocol was changed to a single dose of 500 mg of ciprofloxacin prior to biopsy from February 2015 to April 2017. Patients who had travelled to South East Asia in the 6 months prior to TRPB received a single dose of 1 g intravenous ertapenem prior to biopsy, and this remained unchanged throughout the study period. The rates of infective complication were recorded and compared between the groups of patients who had undergone six doses versus a single dose of prophylactic ciprofloxacin. RESULTS: A total of 766 patients underwent TRPB from August 2011 to April 2017. Of these, 357 patients received the 3-day course of prophylaxis (Group 1) and 409 patients received the single dose prophylaxis (Group 2). Fifty-five patients were excluded from analysis. There was no significant difference in infective complications between the two groups (3.4% (11/326) Group 1 versus 4.9% (19/385) Group 2, P = 0.40). CONCLUSION: Our study supports the use of a single dose of ciprofloxacin as sufficient antibiotic prophylaxis prior to TRPB.

Neobladder Obstruction: A Non-ischemic Cause for Hepatic Portal Venous Gas: Case Report.

Hepatic portal venous gas (HPVG) is a rare ominous radiological sign usually indicative of mesenteric ischemia. Increased detection of HPVG has been associated with a growing number of non-ischemic causes. A 64-year-old gentleman following radical cystectomy and neobladder formation developed clinical signs suggestive of bowel obstruction. HPVG was demonstrated on abdominal imaging. Urgent laparotomy revealed no evidence of ischemia. We hypothesize an obstructed neobladder permitted gas to enter the mesenteric circulation. The patient made a complete recovery with supportive management.