Background/Objectives: Intravesical therapy is associated with a range of side effects. This study assessed baseline self-reported health-related quality of life (HRQoL) scores and examined associations with clinical and demographic variables, as well as lower urinary symptom severity and bother scores, among individuals diagnosed with high-risk non-muscle invasive bladder cancer (NMIBC) prior to initiating intravesical Bacillus Calmette–Guérin (BCG) therapy, either alone or in combination with Mitomycin. Methods: Baseline data were collected from 501 participants with high-risk NMIBC enrolled in the Australian and New Zealand Urogenital Clinical Trials Group (ANZUP) BCG + Mitomycin Clinical Trial, of whom 438 completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C 30, QLQ-NMIBC 24, and the International Prostate Symptom Scoring Tool (IPSS) prior to commencing intravesical treatment. We conducted descriptive and multivariate statistical analyses. We used hierarchical linear regression to examine associations between HRQoL (Global Health Status) and physical functioning, emotional functioning, sexual function, sexual intimacy, and the IPSS total and bother scores. Results: Participants were predominately male (82%), with a mean age of 74.9 years. Over half reported moderate urinary symptoms that affected quality of life. Emotional functioning (β = 0.411, p < 0.001) and physical functioning (β = 0.355, p < 0.001) were the strongest predictors of HRQoL after adjusting for covariates. Conclusions: Individuals diagnosed with high-risk NMIBC report notable physical and emotional concerns prior to commencing intravesical therapy. Targeted interventions may be required to optimise physical and psychological reserve before treatment.

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.

This interim analysis of a multicentre implementation trial (n = 200) evaluated a multimodal artificial intelligence biomarker's impact on shared short-term androgen deprivation therapy (ST-ADT) decisions in intermediate-risk prostate cancer (IR-PC). Biomarker testing altered 27.5% (CI: 21.4-34.2%) of final decisions. ST-ADT use significantly decreased: 70.3% (CI: 58.5-80.3%) of patients initially electing ST-ADT changed to 'NO', versus a 2.4% (CI: 0.5-6.8%) shift to 'YES' (p < 0.001). Decision changes were significantly greater in unfavourable versus favourable IR-PC (35% v 4%; p < 0.001). These interim findings demonstrate a significant shift toward de-escalation.

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.

Background: The role of molecular imaging in urothelial cancer is less defined than other cancers, and its utility remains controversial due to limitations such as high urinary tracer excretion, complicating primary tumour assessment in the bladder and upper urinary tract. This review explores the current landscape of PET imaging in the clinical management of urothelial cancer, with a special emphasis on potential future advancements including emerging novel non-18F FDG PET agents, PET radiopharmaceuticals, and PET-MRI applications. Methods: We conducted a comprehensive literature search in the PubMed database, using keywords such as “PET”, “PET-CT”, “PET-MRI”, “FDG PET”, “Urothelial Cancer”, and “Theranostics”. Studies were screened for relevance, focusing on imaging modalities and advances in PET tracers for urothelial carcinoma. Non-English language, off-topic papers, and case reports were excluded, resulting in 80 articles being selected for discussion. Results: 18F FDG PET-CT has demonstrated superior sensitivity over conventional imaging, such as contrast-enhanced CT and MRI, for detecting lymph node metastasis and distant disease. Despite these advantages, FDG PET-CT is limited for T-staging of primary urothelial tumours due to high urinary excretion of the tracer. Emerging evidence supports the role of PETC-CT in assessing response to neoadjuvant chemotherapy and in identifying recurrence, with a high diagnostic accuracy reported in several studies. Novel PET tracers, such as 68Ga-labelled FAPI, have shown promising results in targeting cancer-associated fibroblasts, providing higher tumour-to-background ratios and detecting lesions missed by traditional imaging. Antibody-based PET tracers, like those targeting Nectin-4, CAIX, and uPAR, are under investigation for their diagnostic and theranostic potential, and initial studies indicate that these agents may offer advantages over conventional imaging and FDG PET. Conclusions: Molecular imaging is a rapidly evolving field in urothelial cancer, offering improved diagnostic and prognostic capabilities. While 18F FDG PET-CT has shown utility in staging, further prospective research is needed to establish and refine standardised protocols and validate new tracers. Advances in theranostics and precision imaging may revolutionise urothelial cancer management, enhancing the ability to tailor treatments and improve patient outcomes.

4577 Background: We hypothesised pembro could be added without undue toxicity to CRT and would improve efficacy in patients (pts) with MIBC. Methods: This multicentre phase 2 trial included people with non-metastatic cT2-T4aN0M0 MIBC (>50% urothelial histology) who declined cystectomy or for whom cystectomy was unsuitable, with no contraindications to CRT or pembro, ECOG performance status 0 or 1, eGFR ≥40 mL/min. Neoadjuvant chemotherapy was not permitted. Pts had maximal TURBT, then whole bladder radiation therapy (RT) (64Gy in 32 daily fractions, mostly IMRT) over 6.5 weeks with weekly cisplatin (35 mg/m 2 IV, 6 doses) and pembro 200mg IV q3wk x 7 doses, both starting with RTx. Surveillance cystoscopy, urine cytology, and CT chest-abdomen-pelvis were performed 12 & 24 weeks after CRT. The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3-4 non-urinary toxicity, or completion of planned CRT within defined parameters (RT < 7 weeks, >1 cisplatin dose omission). Secondary endpoints include rate of complete cystoscopic response without metastatic disease at 12 & 24 weeks, distant metastases free survival (DMFS), overall survival (OS), and loco-regional progression free survival (LRPFS). Longer term follow up (median 54 months) is presented here from the November 2024 analysis. Results: From 2016 – 2021, 28 pts (93% male, median age 72, 96% pure urothelial carcinoma, 29% with carcinoma in situ, 90% pT2) were enrolled at 6 sites. At 48 months, DFMS was 68% (95% CI 46-82%), OS was 64 % (95% CI 42-79%), with median OS not reached (95% CI 25.6m – NE). Local-regional failure free survival at 48 months was 84% (95% CI 63 – 94). Complete response (CR) rate 24 weeks post CRT was 88% (95% CI 70-98%, 23 CR, 3 PD, 2 NE). The The regimen was deemed feasible as previously presented: 6 pts had Gr >3 non-urinary any adverse events (AEs) during treatment or within 12 weeks after completing treatment (2 with delay in RT >7 wks), and 2 pts had cisplatin dose reductions due to G2 AEs. 1 pt had G3 colitis, 1 pt had G2 polymyalgia, 1 pt G2 nephritis. There were no additional immune related adverse events reported with longer follow-up. Conclusions: Longer follow up shows promising OS, DMFS and LRPFS with the combination of CRT and pembro for MIBC. There were no new immune related adverse events. Larger randomised trials to test this approach are ongoing. Clinical trial information: NCT02662062 .

INTRODUCTION:Non-muscle invasive bladder cancer (NMIBC) is a malignancy with a significant recurrence and progression risk. While intravesical Bacillus Calmette-Guérin (BCG) has remained the standard of care for decades, limitations in efficacy, tolerability, and global supply underscore the need for novel therapeutic strategies. Many patients relapse after BCG and are offered radical cystectomy, a highly morbid operation which some are unfit for or decline. Immune checkpoint inhibitors (ICIs) have revolutionized neoadjuvant and advanced bladder cancer therapy. This has driven interest in ICIs as bladder-sparing alternatives in BCG-unresponsive high-risk NMIBC (HR-NMIBC). AREAS COVERED:This scoping review (MEDLINE, Embase, ClinicalTrials.gov; 2015-2025) explores the emerging role of ICIs in NMIBC. It summarizes data from completed and ongoing trials in both BCG-naïve and BCG-unresponsive settings, highlighting key efficacy and safety outcomes. Special emphasis is given to combination approaches and novel delivery routes. EXPERT OPINION:Checkpoint inhibition represents a potentially transformative advance in the bladder-sparing management of NMIBC, particularly in patients unfit for or refusing radical cystectomy. However, widespread adoption will require robust phase III data combined with optimal patient selection to temper concerns regarding toxicity and cost. Ongoing research into combination regimens and local delivery may refine risk-benefit profiles and personalize treatment in the near future.

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.

This case study explores massive tubular ectasia of the rete testes in a patient with Marfan syndrome. Marfan syndrome is a connective tissue disorder and has no known association with tubular ectasia in published research. Despite the unclear pathophysiology of tubular ectasia, potential causes include mechanical obstruction and congenital deformity. The patient, a male in his 40s, presented with bilateral testicular pain and swelling up to a volume of 200cc over two years. Tubular ectasia was diagnosed on ultrasound and MRI, no obstructive aetiology was identified. Initial conservative management was chosen, but further enlargement led to reconsideration of treatment options.