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.

Nurse-led telephone notification of a prostate cancer diagnosis: Prospective analysis of men's preferences for and experiences of a same-day assessment and diagnostic clinic.

OBJECTIVE: The 'One Stop Prostate Clinic' (OSPC) was a same-day prostate cancer assessment and/or diagnostic clinic. Preferences and experiences of men who received initial telephone notification of their prostate biopsy results (cancer or benign) by the OSPC Clinical Nurse (CN) are reported. METHODS: Prospective mixed methods study using survey instrument and thematic analysis of OSPC preferences and experiences. RESULTS: One thousand men attended the OSPC between August 2011 and November 2017, 876 underwent prostate biopsies; 790/876 (90%) men consented to telephone notification of biopsy results, 5/876 (1%) declined and 79/876 (9%) were ineligible/not contacted. 220/403 men (55%) returned the OSPC questionnaire; 135/220 (61%) men received a cancer diagnosis, 119/132 (90%) would choose this method again and 7/132 (5.5%) would not and 6/132 (4.5%) were unsure; 94/135 (70%) reported no disadvantages with this notification method. Overall satisfaction rate with the OSPC was 96% (209/218) men. CONCLUSION: Initial telephone notification of prostate biopsy results by the OSPC CN was preferred by the vast majority of eligible men. Many men with a cancer diagnosis did not experience any disadvantages. This method of results delivery can be incorporated by other tumour groups.

ProCare Trial: a phase II randomized controlled trial of shared care for follow-up of men with prostate cancer.

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.

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.

A randomised controlled trial comparing use of lignocaine periprostatic nerve block alone and combined with diclofenac suppository for patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy.

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.

Analysis of the financial impact and efficiency of the One Stop Prostate Clinic: A same day prostate cancer diagnostic clinic in the Australian public health system.

Background: Access to prostate cancer diagnostic clinics are challenging for rural men in Western Australia due to remoteness and long travel distances. The One Stop Prostate Clinic (OSPC) provided same day assessment and diagnosis for prostate cancer in a public tertiary hospital to reduce access barriers for rural men. The objective of this study was to determine the financial and resource utilisation impact of the OSPC compared to a usual care pathway (UCP). Design and methods: Study design: Cost minimisation analysis of the OSPC model (assuming 100% new referrals) compared with a UCP, including impact on the Patient Assisted Transport Scheme (PATS) for rural men. An estimate of total cost comparison of OSPC and UCP pathways of outpatient and diagnostic costs was calculated based on journey mapping of attendance and follow up. Methods: Prospective data collection between August 2011 and November 2017 of referral, attendance and follow up outcomes. Journey mapping to identify time from referral to diagnosis, number of outpatient appointment (OPA) and travel savings. Results: A total of 1000 men attended - 466 (47%) rural and 534 (53%) metro. Mean time from referral to diagnosis was 57 days (rural) versus 63 (metro; p = 0.034)). The OSPC saved 543 travel episodes (distance of 1.5M km) and 658 OPA's. Total episode of care costs for the OSPC (100% new) pathway estimated as $2237.34, compared to $2847.00 for a UCP, generating savings of $609.66 per attendance ($609,658.22 overall). Conclusion: The OSPC was more cost effective and efficient in comparison to a UCP.

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.

Ten-year outcomes of the first 'one-stop haematuria clinic' in an Australian public hospital.

BACKGROUND: Urgent assessment of haematuria is critical to exclude malignancy. The utilization of haematuria clinics in Australia remains in its infancy. It is hoped that the streamlined investigative service will achieve earlier diagnosis of urological malignancy and subsequently decrease morbidity and mortality. We report the 10-year prospectively collected outcomes from Australia's first dedicated one-stop haematuria clinic (OSHC). METHODS: Since its commencement in May 2008 through to July 2018, all consecutive patients assessed in the OSHC were included in the analysis. Data collected included demographics, presentation, wait times, investigation, assessment, initial treatment, referral and histopathology. RESULTS: A total of 3008 patients were seen in the OSHC with non-visible haematuria (1024, 34%) and visible haematuria (1984, 66%). Three hundred and twenty-seven (10.9%) patients were diagnosed with urothelial malignancy. In all, 306 (10.2%) patients had lower tract disease and 21 (0.7%) had upper tract disease. Urothelial cases were compiled of 123 (37.6%) Ta LG, 39 (11.9%) Ta HG, 21 (6.4%) Tis, 67 (20.5%) T1 and 77 (23.6%) T2-4. Urothelial malignancy was diagnosed more often in males (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.35-2.25), older patients elder than 60 years (OR 1.97, 95% CI 1.47-2.64) and patients with visible haematuria (OR 5.42, 95% CI 3.73-7.86). In all, 53.4% of patients were discharged after a single visit to the OSHC. CONCLUSION: The OSHC has served as an effective tool for rapid, streamlined assessment of patients presenting with haematuria. This model of care has been subsequently adopted by numerous public centres across Australia. Current funding structures present a barrier to this excellent approach for rapid access diagnostics.

'One Stop Prostate Clinic': prospective analysis of 1000 men attending a public same-day prostate cancer assessment and/or diagnostic clinic.

BACKGROUND: This study reported the outcomes of the first 1000 men to attend the One Stop Prostate Clinic, a consultant-led same-day prostate cancer assessment and diagnostic clinic at a tertiary public hospital. METHODS: Prospective audit of demographic and clinical data between August 2011 and November 2017 was conducted for same-day urological assessment and/or trans-rectal ultrasound (TRUS)-guided prostate biopsies with peri-prostatic infiltration local anaesthetic (PILA) and antibiotic prophylaxis. RESULTS: A total of 466 (47%) rural and 534 (53%) metropolitan men attended. Rural mean (range) age was 63 years (38-86) and 65 years (37-89) for metro men (P = 0.006). Rural median (range) prostate specific antigen (PSA) level was 6.7 g/mL (0.2-450) and 7.3 ng/mL (0.5-860) for metro men (P = 0.011). Twenty-five men (2.5%) refused/could not tolerate TRUS-guided biopsy using PILA. One hundred and fifty-one (15%) men had multi-parametric magnetic resonance imaging prior to TRUS biopsy and 876 (88%) men had prostate biopsies, with a new cancer diagnostic rate of 51% (443 men). Clinically significant prostate cancer was detected in 339 (34%) men. The overall infective complication rate requiring hospital admission rose from 1.4% to 2.9% after the prophylactic antibiotic regimen changed from six doses of 500 mg ciprofloxacin to a single dose of 500 mg (P = 0.398). CONCLUSION: This is the largest single institution prospective TRUS prostate biopsy series in Australasia. Biopsies using PILA were well tolerated with low complication rates and diagnosed a high rate of clinically significant prostate cancer. The 'One Stop' pathway generates efficiencies with combined assessment and diagnostic process, lessens demand on outpatient clinic appointments and reduces travel time and costs for rural men.

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.

Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer.

INTRODUCTION: Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. METHODS AND ANALYSIS: The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. RESULTS: of this phase II trial will be reported in peer-reviewed publications and in conference presentations. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12610000938000.