Peter MacCallum Cancer Centre

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

Accurately resolving the full spectrum of somatic alterations remains a major barrier in cancer genomics. Current short-read sequencing methods often prioritize SNVs and copy-number changes while overlooking SVs, haplotype-specific events, and epigenetic dysregulation. To bridge this gap, we present TumorLens, the first unified long-read framework that jointly detects SNVs, indels, SVs, large CNVs, loss-of-heterozygosity, and CpG methylation in a single assay. TumorLens introduces purity-aware long-read CNV/LoH modeling and personalized HLA-locus reconstruction, enabling the mechanistic interpretation of immune escape through allele-specific methylation profiling. Benchmarked across GIAB standards and clinical cohorts, TumorLens accurately recovered key somatic events, including interferon locus disruptions and HLA loss. Furthermore, it revealed pervasive global hypomethylation alongside focal hypermethylation in critical oncogenic pathways. By consolidating multi-omic layers into an end-to-end analytic pipeline, TumorLens establishes a new standard for comprehensive tumor profiling, accelerating the translation of long-read sequencing into precision oncology.

Penile cancer is a rare malignancy, with an Australian incidence of 0.6 in 100 000 men, with a wide range of clinical presentations, from localised, curable tumours to aggressive forms with high morbidity and mortality. Epidemiological data and management guidelines for penile cancer in Australia are limited. The Australian Penile Cancer Clinical Registry (APCCR) aims to address this gap through a centralised database studying local risk factors, treatment effectiveness, and outcomes. The APCCR is a national, multicentre, prospective clinical quality registry. The primary objective is to map demographic and tumour characteristics, human papillomavirus infection rates, long-term surgical and non-surgical (radiotherapy and chemotherapy) interventions in penile cancer. Secondary objectives include elucidating disparities and interdisciplinary gaps in care and identifying areas for further studies. The registry aims to capture adult men with penile cancer in, utilising retrospective data collection and a prospective cohort design. Retrospective data are extracted from existing medical records, and prospective data are collected at enrolled sites. The registry is built in Research Electronic Data Capture (REDCap) and hosted on BioGrid Australia servers, enabling standardised data collection. Registration with the Australian Register of Clinical Registries is pending approval. The pilot phase of the APCCR is currently operational, with ongoing site recruitment. Five sites in Victoria and New South Wales are currently enrolled in the registry. The APCCR Steering Committee determined reporting and data protocols to ensure accurate data collection. The dataset was developed to comprise relevant clinical metrics on penile cancer diagnosis, disease, intervention, and surveillance. The APCCR is a robust platform for furthering the understanding of penile cancer diagnostic and treatment practices in Australia, aiming to further research and clinical practice changes. This will drive further collaboration and improvements in outcomes for Australian men affected by penile cancer, particularly with ongoing national expansion and improved longitudinal data.

Immunotherapy has been a pillar of the renal cell carcinoma (RCC) treatment landscape for over three decades. Some of the earliest cancer immunotherapies available, such as interleukin 2 and interferon-alpha, have resulted in complete responses, but only in a small number of patients. Immune checkpoint inhibitors (ICIs), however, have demonstrated improved response rates and prolonged survival for a greater number of patients, fully transforming the standard of care in first-line and subsequent-line settings. More recently, ICIs are also being used in the adjuvant setting for high-risk patients. However, treatment with ICIs requires a nuanced understanding of topics such as patient selection, histology and risk considerations, and integration with local therapies. As such, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline (CPG) on immunotherapy for the treatment of RCC. Drawing from published data and clinical experience, the Expert Panel developed evidence-based and consensus-based recommendations. Topics include therapy selection in the adjuvant and metastatic settings, considerations for special patient populations, response monitoring, and patient education and quality of life considerations, among others, with the goal of improving patient care by providing guidance to the oncology community.

Several genomic risk stratification tests are available to predict the risk of metastasis and mortality for prostate cancer patients at the time of diagnosis. However, the evidence supporting the clinical utility of genomic risk stratification tools is fragmented, posing challenges in assessing their real-world clinical impact and cost-effectiveness. To review and summarise the clinical impact and health economic evidence of the four types of genomic risk stratification tests and to validate their clinical impact and health economic evaluation outcomes. A systematic search was conducted in the Scopus, EMB Reviews and Google Scholar databases. Eligible publications were selected based on the eligible patient cohort, genomic test, initial NCCN risk categories, the clinical impact of the genomic test and health evaluation outcomes. 26 clinical impact evidence studies and four health economic evaluation studies were included. Most clinical studies indicated that genomic tests reclassified patients' risk predictions into both lower- and higher-risk groups. The reclassification outcomes influenced patients' treatment decisions between active surveillance and radical treatment. The prognostic value of the genomic tests was validated in terms of biopsy upgrade, metastasis and death. The limited number of health economic studies reported that the Oncotype DX Prostate Score and ProMark were cost-effective, while the Prolaris was cost-saving in the US but not in Canada. The evaluation of the Decipher Genomic Classifier at the time of diagnosis was not available. More long-term clinical evidence is needed, as are updated health economic evaluations, to determine the cost-effectiveness of integrating genomic risk stratification into prostate cancer treatment decision-making in clinical practice.

168 Background: In the phase 3 TALAPRO-2 study, talazoparib (TALA) + enzalutamide (ENZA) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) vs placebo (PBO) + ENZA as first-line treatment (tx) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) unselected (cohort 1) and selected for homologous recombination repair gene alterations (HRRm cohort). Here, we report post-hoc analyses of PSA kinetics from the final OS analysis cutoff date. Methods: Pts were randomized 1:1 to ENZA 160 mg + either TALA 0.5 mg or PBO once daily. The primary endpoint was rPFS; OS, a key secondary endpoint. We performed post hoc analyses of PSA flare (defined as a rise in PSA above baseline followed by a return to baseline or lower within 12 months), PSA response ≥50% (PSA50), PSA response ≥90% (PSA90), undetectable PSA (defined as PSA <0.2 ng/mL), and duration of PSA response. OS and rPFS were analyzed in PSA50 responders. Results: At data cutoff (Sep 3, 2024), PSA flare was observed in 2–3% of pts in both tx arms of the unselected and HRRm cohorts (Table). The median time for PSA to decline back to or below baseline after a rise above baseline was 57 days in both tx arms in the unselected cohort, and 60 and 117 days with TALA + ENZA and PBO + ENZA, respectively, in the HRRm cohort (Table). A greater proportion of pts taking TALA + ENZA achieved PSA50, PSA90, and undetectable PSA compared with PBO + ENZA in both cohorts (Table). In both cohorts, pts in the TALA + ENZA arm also had a longer median duration of PSA50 response, PSA90 response, and undetectable PSA vs PBO + ENZA (Table). In the unselected cohort, rPFS and OS directionally favored TALA + ENZA vs PBO + ENZA in PSA50 responders (rPFS HR: 0.72 [95% CI 0.57, 0.89], median 39.8 vs 27.6 months; OS HR: 0.90 [0.72, 1.13], median 53.3 vs 47.3 months). Similarly, in the HRRm cohort, rPFS and OS favored TALA + ENZA in PSA50 responders (rPFS HR: 0.51 [0.38, 0.70], median 36.1 vs 18.3 months; OS HR: 0.62 [0.44, 0.86], median not reached vs 38.2 months). Conclusions: In both cohorts, a greater proportion of pts in the TALA + ENZA arm achieved PSA responses with longer durations vs PBO + ENZA. Also, PSA flare was unusual (2–3%) and resolved in ~60 days (both cohorts) with TALA + ENZA vs ~60 days (unselected) and ~120 days (HRRm) with PBO + ENZA. In both cohorts, OS and rPFS numerically favored TALA + ENZA vs PBO + ENZA in PSA50 responders. Analyses of PSA responses for specific genes (e.g. BRCA2 ) are underway. Clinical trial information: NCT03395197 . Unselected Cohort HRRm Cohort TALA + ENZA (n=402) PBO + ENZA (n=403) TALA + ENZA (n=200) PBO + ENZA (n=199) PSA flare, n (%) 12 (3) 11 (3) 5 (2) 5 (3) Median time for PSA decline back to or below baseline, days 57 57 60 117 PSA50, n (%) 335 (83) 285 (71) 173 (86) 126 (63) Median duration, days 430 284 420 225 PSA90, n (%) 253 (63) 182 (45) 139 (70) 80 (40) Median duration, days 480 419 589 308 Undetectable PSA, n (%) 159 (40) 107 (27) 87 (44) 44 (22) Median duration, days 644 539 650 365

17 Background: VIR-5500, a dual-masked, PSMA-targeted bispecific T-cell engager, is designed to be specifically activated in the tumor microenvironment where protease activity is dysregulated relative to healthy tissues, potentially expanding the safety margin and therapeutic index. Methods: VIR-5500 was administered IV weekly (QW) and every 3 weeks (Q3W) at doses of 30 - 4000 ug/kg to eligible participants (pts) with progressive mCRPC after receiving SOC. Objectives were to characterize safety, pharmacokinetics (PK) profiles, anti-tumor activity, and determine the dose(s)/regimen(s) for expansion (NCT05997615). Results: As of 23 September 2025, 51 heavily pretreated mCRPC pts (~95% post-taxane) received ≥ 1 dose of VIR-5500. No dose limiting toxicities (pre-defined toxicities occurring during cycle 1) were reported. The incidence of related Grade ≥ 3 AEs was low and CRS was mostly limited to grade 1 and 2 (see Table). PSA declines were noted in all pts dosed at ≥ 3000 ug/kg Q3W, including clinically significant and deep PSA reductions (91% PSA 50 and 55% PSA 90 ). Preliminary evidence of durable PSA responses lasting over one year was noted in select patients undergoing intrapatient dose escalation. An objective response rate of 67% was observed in 4 out of 6 RECIST-evaluable patients treated at doses ≥ 3000 µg/kg Q3W, including one confirmed partial response and three additional partial responses pending confirmation. PSMA-PET imaging confirmed anti-tumor activity, demonstrating strong concordance with PSA 90 responses. Evidence of T-cell activation and target engagement included increased on-treatment CD3+ T-cell tumor infiltration and serum IFN-γ, including minimal elevation of IL-6 levels, consistent with generally low-grade CRS. Preliminary analyses indicated PK was dose-proportional for VIR-5500, with a half-life of approximately 8-10 days and minimal systemic unmasking to the fully unmasked metabolite. Dose escalation continues with both QW and Q3W regimen, and updated data will be provided at the time of the presentation. Conclusions: Pending further clinical validation, available data are suggestive of a generally favorable safety profile, with evidence of meaningful anti-tumor activity, including RECIST responses, and preliminary evidence of durable benefit in a heavily pretreated population with substantial disease burden. Clinical trial information: NCT05997615 . All Participants(n/N, %) ≥ 3000 ug/kg Q3W(n/N, %) Gr 1 CRS 24/51, 47% 9/15, 60% Gr 2 CRS 4/51, 8% 1/15, 7% Gr ≥ 3 CRS 1/51, 2% 0/15, 0% Related Gr ≥ 3 TEAE 8/51, 16% 3/15, 20% Any PSA Decline 34/45, 76% 11/11, 100% PSA 50 24/45, 53% 10/11, 91% PSA 90 11/45, 24% 6/11, 55% Objective Response Rate 4/22, 18% 4/6, 67%

Prostate-specific membrane antigen (PSMA) is a surface membrane antigen that is highly overexpressed in prostate cancer, with heterogenous expression throughout the natural history of the disease. This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer. We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes. A search on PubMed, Medline, and Web of Science was performed using the following keywords: "PSMA", "Prostate Specific Membrane Antigen", "Prostate cancer", "Biomarker", "Diagnosis". We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review. Key articles assessing the biology of PSMA, as well as its use as a potential diagnostic and therapeutic target in early prostate cancer, were assessed. The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed. The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed, along with any current evidence to support their use in early prostate cancer. PSMA is heavily expressed throughout the early stages of prostate cancer, and this has significant therapeutic implications. There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis, risk stratification, and prognostication of localised prostate cancer. PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer; however, this remains an area of ongoing research.

A major limitation to robotic training internationally is sufficient access to console and bedside operating time. It is important that trainees are “robot ready” when clinical opportunities arise. Delivering the didactic component of training in advance of hands-on training opportunities is needed to maximise the efficiency of console time. This study describes the development and implementation of a platform agnostic online curriculum (Foundations in Robotic Surgery -IMRA) that provides an overview of robotic surgery as didactic learning prior to hands-on experience. Curriculum development is reported using Kern’s model. A literature review was conducted in accordance with the PRISMA statement. A mixed-methods approach, incorporating surveys and semi-structured interviews, defined learning objectives and curriculum content. Curriculum outcomes were assessed via surgeon surveys, and modifications were made based on feedback from the Royal Australasian College of Surgeons. The literature review revealed a gap in vendor-neutral online curricula for robotic surgery. Six experts comprising of general surgeons and urologists, identified key learning objectives on safety, communication, and surgical technique. This gap was addressed by developing an online curriculum comprising of ten theory modules. In the development group (n = 28; 16 responses), Kirkpatrick assessment showed a 60% increase in participants rating their knowledge as good or excellent. Confidence in bedside assistance and console training rose by 37.5%. In the rollout group (n = 108; 88 responses), 89.8% rated the content quality as good or excellent. Development and implementation of the IMRA Foundations in Robotic Surgery Curriculum demonstrated improvements in learners’ self-rated knowledge and confidence in both bedside and console aspects of multi-platform robotic surgery.