BACKGROUND AND OBJECTIVE:Intravesical bacillus Calmette-Guérin (BCG) plus mitomycin (MM) had not been compared rigorously with BCG alone in BCG-naïve, non-muscle-invasive bladder cancer (NMIBC) patients. METHODS:Participants with BCG-naïve NMIBC (high-grade pTa or any grade pT1; concurrent carcinoma in situ [CIS] allowed) were assigned randomly (1:1) to either the BCG + MM or the BCG-alone group after maximal transurethral resection. The primary endpoint was disease-free survival (DFS); the secondary endpoints included a complete response on cystoscopy at 3 mo (CR3mos), recurrence, progression, adverse events (AEs), and deaths from any cause. KEY FINDINGS AND LIMITATIONS:We randomised 501 participants (249 to BCG + MM and 252 to BCG alone), with pTa in 53%, pT1 in 47%, and concurrent CIS in 28%. The median follow-up was 48 mo. DFS was not superior for BCG + MM versus BCG alone (2-yr DFS rate: 75% vs 71%; hazard ratio 0.87, 95% confidence interval 0.65-1.16; p = 0.3). The numbers of events for BCG + MM versus BCG alone were as follows: 214 versus 210 (CR3mos), 79 versus 86 (recurrence), 28 versus 44 (progression), and 26 versus 23 (death). Those assigned BCG + MM had more instillations (4033 vs 3383) but fewer doses of BCG (total 2056 vs 3383; median nine vs 16) than BCG alone. Grade 3-5 AEs occurred in 43 assigned BCG + MM versus 37 assigned BCG alone. A higher number of participants assigned BCG + MM than those assigned BCG alone had ≥75% of their planned doses (78% vs 68%, p = 0.02). CONCLUSIONS AND CLINICAL IMPLICATIONS:BCG + MM was not proved superior to BCG alone, but required 39% fewer doses of BCG and fewer treatment discontinuations. These findings support consideration of BCG + MM as a pragmatic alternative to BCG alone, which could mitigate the global shortage of BCG.

TPS903 Background: Sub-urothelial injection of durvalumab presents a novel therapeutic approach for bladder cancer. SUBDUE-1, a first-in-human Phase Ib dose escalation study presented at ASCO 2022, demonstrated the safety and tolerability of sub-urothelial durvalumab in patients with bladder cancer scheduled for radical cystectomy, with no treatment-related adverse events and preliminary evidence of immunomodulation in the tumour microenvironment 1 . SUBDUE-3 will use radiolabelled 89 Zirconium-durvalumab ( 89 Zr-durvalumab) to define local and systemic biodistribution following sub-urothelial injection. Methods: SUBDUE-3 is an open-label, non-randomized Phase 0 trial sponsored by ANZUP (ANZUP 2402, ACTRN 12624001245583p). Ethics approval has been obtained for this study which is currently recruiting patients diagnosed with either high-risk non-muscle-invasive bladder cancer (HR-NMIBC) or muscle-invasive bladder cancer (MIBC), scheduled for radical cystectomy. 25mL of sub-urothelial 89 Zr-durvalumab will be injected in 1mL aliquots throughout the bladder using a 5Fr Bonee needle via 22Fr rigid cystoscope at a GA cystoscopy performed 2 weeks pre-cystectomy. After injection, PET imaging will be performed at several time points over 7 days. At each imaging time point, blood samples will be collected to evaluate the systemic bioavailability of 89 Zr-durvalumab using a gamma counter. Additionally, the urinary radiation dose will be measured during the first imaging session. Quality control measures will assess dissociation of 89 Zr from durvalumab. Dosimetric analyses will determine the distribution and radiation dose of 89 Zr-durvalumab both within the bladder and systemically, providing critical insights for future therapeutic strategies in bladder cancer treatment. Primary endpoint: visual and semi-quantitative assessment of 89 Zr-durvalumab distribution within the bladder wall and systemic organs (liver, kidney, lung, bone marrow) via PET imaging. Secondary endpoints: bladder and other organ tracer biodistribution; comparison of dosimetry data with cohorts receiving systemic 89 Zr-durvalumab; safety; feasibility. The trial has a one-year recruitment strategy aiming to recruit up to 3 patients and is expected to finish recruiting in 2025. References: 1. Hayne D. Et al. The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer. BJU Int. 2024 Aug;134(2):283-290. doi: 10.1111/bju.16325. Epub 2024 Mar 12. PMID: 38469652. Clinical trial information: ACTRN 12624001245583p.

TPS897 Background: Treatment options are notably limited for BCG-unresponsive high-risk non-muscle invasive bladder cancer (HR-NMIBC), often involving intravesical chemotherapy or radical cystectomy. If a patient is unsuitable for cystectomy, or they decline, guidelines suggest intravesical chemotherapy utilizing a combination of gemcitabine and docetaxel 1,2 . Traditionally, these drugs have been administered sequentially with no previous studies investigating synchronous intravesical instillation of gemcitabine-docetaxel. Synchronous treatment has potential resource and time-utlization advantages but has not been formally studied. Methods: G-DISCO (ANZUP 2403, ACTRN12624001188527p) is a single-arm, Phase I study designed to assess the feasibility, safety, and tolerability of synchronous intravesical instillation of gemcitabine and docetaxel. The study has Ethics approval and is currently recruiting patients with fully resected HR-NMIBC that is unresponsive or unsuitable for intravesical BCG therapy and where the patient is unwilling or unable to undergo radical cystectomy. Participants will receive synchronous intravesical administration of gemcitabine (1 g) and docetaxel (37.5 mg), both agents constituted together in 50 mL of saline. The combined solution will be administered via urinary catheter with a recommended minimum dwell time of 60 minutes, aiming for an optimal dwell time of 90 minutes. This intravesical treatment will be repeated weekly for six weeks. This study will enroll 15 patients and has a two-year recruitment strategy expected to finish recruiting in 2026. Feasibility of synchronous intravesical administration of gemcitabine and docetaxel will be assessed by the completion rates of the planned six-week course. Safety will be monitored through the recording of adverse events and tolerability will be evaluated using AUA-SI / IPSS, and NMIBC-SI. Secondary endpoints include; recurrence rates at three months post-treatment, effects of regimen on carbon footprint, pharmacokinetic impacts of combined administration, and tissue translational end-points. If successful, G-DISCO could establish a new standard for administering intravesical gemcitabine-docetaxel, offering several potential advantages including shortened treatment time for patients, improved unit time-efficiency and resource savings for healthcare facilities, and reduced exposure for staff handling these cytotoxic agents. References: 1. Holzbeierlein JM et al. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment. J Urol. 2024;211(4):533-8. 2. Bladder intravesical DOCEtaxel and gemcitabine 2023 [cited 2024 09 Jul]. Available from: https://www.eviq.org.au/medical-oncology/urogenital/bladder-and-urothelial/4320-bladder-intravesical-docetaxel-and-gemcitabin Clinical trial information: ACTRN12624001188527p.

Urothelial carcinoma in situ represents a high-grade, high-risk form of urothelial cancer which predominantly occurs within the bladder, rarely affecting other structures within the genitourinary system such as the seminal vesicle. Involvement could represent more advanced disease, necessitating more aggressive management. We present a case of CIS involving the entire urinary tract in a renal transplant patient who underwent a complete urinary tract extirpation (CUTE) for BCG-refractory CIS of the bladder. This case is unique, representing the first reported CUTE with malignant involvement of every site in the urinary tract.

LBA4504 Background: Intravesical BCG is the standard of care for high-risk non-muscle invasive bladder (NMIBC) after maximal transurethral resection. Availability and access to BCG have been a global challenge since 2013. We sought to determine the efficacy and safety of intravesical treatment with BCG plus mitomycin (BCG+MM) compared with BCG-alone for high-risk, BCG-naïve NMIBC. Methods: This was an open-label, randomized, phase 3 trial. Eligible participants (pts) had high-grade papillary urothelial cancer stages pTa/pT1; concurrent CIS was allowed. Pts were randomly assigned BCG+MM vs BCG-alone. The BCG+MM regimen was weekly induction x 9 (BCG wks 1, 2, 4, 5, 7, and 8; MM wks 3, 6, and 9) followed by 4-weekly maintenance x 9 (MM wks 13, 17, 25, 29, 37, and 41; BCG wks 21, 33, and 45: total of 9 BCG doses). The BCG-alone regimen was weekly induction x 6, then 4-weekly maintenance x 10: total of 16 BCG doses. The primary endpoint was disease-free survival (DFS) at 2 years; secondary outcomes included complete response on cystoscopy at 3 months (CR3mos), time-to-recurrence (TTR), time-to-progression (TTP), overall survival (OS) and adverse events (AE). The target sample size of 500 provided 85% power to detect an absolute improvement of 10% in DFS at 2 years with a type-1 error rate of 0.05. Cox regression was used to calculate hazard ratios (HR), confidence intervals (CI), and account for competing risks. P-values are 2-sided and not adjusted for multiple comparisons. Clinicaltrials.gov NCT02948543. Results: We enrolled 501 pts from DEC2013 to MAY2023: median age 70 years (IQR 63-77); pTa 53%, pT1 47%, concurrent CIS 28%. In this primary analysis, the median follow-up was 47 months (IQR 31-64) at the data cut-off of 06DEC2024. Analyses of all key endpoints (DFS, CR3mos, TTR, TTP and OS) supported similar efficacy in the 2 treatment groups (see table), but none with p<0.05. The total numbers of instillations were higher for BCG+MM than BCG-alone (4,034 vs 3,383), whereas the total doses of BCG (2,056 vs 3,383), and median doses of BCG per pt (9 vs 16) were lower for BCG+MM than BCG-alone. The numbers of pts with grade 3-5 AEs were 43 in BCG-MM vs 37 in BCG-alone. The AE (of any grade) reported by the highest numbers of pts (BCG+MM vs BCG-alone) were fatigue (109 vs 110), renal/urinary (78 vs 83), and flu-like symptoms (34 vs 60). More pts had ≥75% of their planned doses with BCG+MM than BCG-alone (78% vs 68%; p=0.02). Conclusions: BCG+MM had similar efficacy and safety, but with fewer treatment discontinuations and fewer doses of BCG than BCG-alone. BCG+MM is a good alternative to BCG-alone. Clinical trial information: NCT02948543 . BCG+MM N=248 BCG-aloneN=252 HR (95% CI) p-value DFS at 2 years 76% 71% 0.86 (0.64-1.14) 0.30 CR at 3 months 90% 86% 1.05 (0.98-1.12) 0.22 Recurrence-free at 2 years 81% 75% 0.84 (0.61-1.18) 0.31 Progression-free at 5 years 87% 81% 0.74 (0.45-1.21) 0.23 OS at 5 years 87% 87% 1.07 (0.61-1.88) 0.81

BACKGROUND:This study determined, implemented, and assessed a nurse-led radical cystectomy follow-up protocol. METHODS:In 2021, an evidence-based risk-stratified protocol (non-urological cancers and benign [N-UC&B], low, or high risk) was developed from current guidelines, local and national expert opinion, and after formal discussion with the Urological Society of Australia and New Zealand (USANZ) Western Australia (WA) and Australia and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Retrospective and prospective assessment of cystectomy follow-up occurred between 2015 and 2023. Patients received 'surgeon-led' follow-up March 2015 to August 2021, and 'nurse-led' follow-up August 2021 to April 2023. Adherence to follow-up, cost-analysis, and healthcare efficiency calculations were performed. RESULTS:Of 176 cystectomy patients, 159 (90.3%) were eligible for inclusion. Overall adherence to nurse-led follow-up was 78.6% compared to 43.4% in surgeon-led (P < 0.001). Adherence to nurse-led follow-up was higher in all risk categories (high-risk 79.1% vs. 43%, P < 0.001; low risk 75% vs. 52.3%, P = 0.110; N-UC&B 71% vs. 30%, P = 0.153). Nurse-led consultation saved $59.50 per consultation with overall cost savings of $179.50, $416.50, and $595 for the entire follow-up period for N-UC&B, low, and high-risk groups based on consultation alone. A total of 1072 appointments (536 h, $62 390.40) would have been saved if the surgeon-led cohort of patients were seen in nurse-led clinics. CONCLUSION:Protocol driven nurse-led cystectomy follow-up demonstrates excellent adherence and may be more cost-effective than surgeon-led follow-up.

Objective: Specialist genitourinary (GU) nurses provide care to a broad and diverse group of patients diagnosed with kidney, bladder, prostate, testicular, adrenal, and penile cancer. The purpose of this study was to identify GU cancer nurse perspectives of perceived unmet needs in service provision, specific educational and research priorities. Methods: A concurrent mixed methods study design incorporated quantitative and qualitative data collection from the GU Cancer nurses workforce in Australia. Quantitative data collected using an electronic survey instrument and were analysed using descriptive statistics. Qualitative data collected through semi-structured interviews and coded for thematic analysis. Ethical approval was gained. Results: Fifty responses were received from the electronic survey. 39/50 (78%) were female and 35 (70%) were metropolitan based. The highest domains of perceived unmet needs related to psychological/emotional needs - 17/23 (74%), intimacy needs - 15/23 (65%) and informational needs - 13/23 (57%). The themes from the qualitative interviews identified: (1) Patient needs - lack of tumour specific contact for cancer patients, fragmented delivery of cancer care, perception of better access to supportive care for public patients, lack of access to supportive care screening tools for needs assessment. (2) Educational needs - lack of GU specific cancer educational resources/learning opportunities and barriers to accessing educational opportunities. (3) Research priorities - impact on carers/partners, specific needs of different GU cancers, future focus on genetic testing/ counselling, interventions for financial toxicity and development of models of care for geriatric GU patients. Conclusions: Specialist GU cancer nurses support a broad group of patients. Given the prominence of addressing unmet cancer care needs among people with GU cancers in this study, cancer nursing as a discipline alongside the multidisciplinary team, requires innovative solutions to overcome fragmented care which is often highly complex, and develop individualised and integrated care across the cancer care continuum. We encourage clinicians, researchers, policy makers, people affected by cancer, and their care networks, to continue to drive innovation by (1) Embedding an integrated approach to cancer nursing, (2) Implementation of shared care, (3) Implementation of patient navigation, (4) Embracing emerging technologies, (5) Future focus on education, and (6) Future focus on nurse-led research.

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.

TPS4617 Background: Adjuvant intravesical BCG decreases disease recurrence and progression in high-risk, NMIBC, however recurrence occurs in 30% of those affected, despite optimal therapy. Meta-analyses evaluating addition of intravesical MM to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Phase 3 randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will determine the effects of adding MM to the standard BCG after resection of high-risk NMBIC. This is the largest study evaluating this approach in high-risk NMIBC, is of particular relevance given the current BCG shortage, and has the potential to change global practice. Methods: This open-label phase 3 trial is randomizing 500 participants stratified by stage, site of disease, and presence of carcinoma in-situ, in a 1:1 ratio to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG weeks 1, 2, 4, 5, 7, 8; months 4, 5, 7, 8 + MM weeks 3, 6, 9; months 3, 6, 9, see figure below). This provides 85% power to detect an absolute improvement of 10% in 2-year disease free survival (DFS) at 2p = 0.05. Stage 1 (n = 130) was to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, established feasibility. Stage 2, including an additional 370 participants, will provide information on DFS, time to recurrence and progression, overall survival, and identification of potential predictive biomarkers, is estimated to complete accrual by Q2 2023. Progress As of Jan 2023, 484 of 500 planned participants have been recruited from 16 Australian and 1 UK site. In stage 1, successful treatment completion, defined as 75% or more of planned treatment doses, was achieved by 76% in the experimental group (BCGMM) versus 60% in the control group (BCG alone). Clinical trial information: NCT02948543 .

ABSTRACT 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.

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.