Prostate Cancer Foundation of Australia

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.

Androgen deprivation therapy (ADT) has been pivotal in advanced prostate cancer (PCa) for decades. The introduction of androgen-receptor pathway inhibitors (ARPIs) has transformed treatment paradigms. However, their real-world adoption over time has not been comprehensively characterised. We examined prescribing trends for androgen-directed therapies in Australia over a 29-year period. A retrospective population-based analysis of Pharmaceutical Benefits Scheme (PBS) dispensing data (1996-2024) was performed. PBS-listed anti-androgen therapies-luteinising hormone-releasing hormone (LHRH) agonists (goserelin, leuprorelin, triptorelin), combined androgen blockage (CAB) (LHRH + bicalutamide), ARPIs (enzalutamide, apalutamide, darolutamide, abiraterone)-were included. Annual prescription counts were standardised per 100,000 men. Outcomes included temporal trends, proportional contribution of each drug class, and the effect of ARPI introduction using interrupted time-series (ITS) analysis. Anti-androgen prescriptions rose from 146 to 228,707 between 1996 and 2024, respectively. LHRH monotherapy accounted for > 94% of prescriptions prior to ARPI approval, declining to 51.61% in 2024 despite continued absolute growth (+ 65.16 prescriptions/100,000/year, p < 0.0001). ARPIs expanded following PBS listing, increasing from 2.44% in 2013 to 47.28% in 2024 (+ 131.9 prescriptions/100,000/year, p < 0.0001). ITS modelling demonstrated a significant immediate level increase of + 9.85 percentage points (p < 0.0001) and sustained a post-intervention slope increase of + 3.04 percentage points per year (p < 0.0001) following ARPI introduction, closely mirroring observed proportional and absolute growth 3.44-47.28% between 2013 and 2024, respectively. Australia has transitioned from predominately LHRH-based therapy to widespread use of ARPIs. Health-system structures enabling timely clinical access appears pivotal to the rapid and equitable diffusion of high-value androgen-targeted therapies.

ABSTRACT This study explores the factors associated with financial risk tolerance using data from a panel of 1334 investors collected between February and May 2023 across Australia, the United Kingdom, and the United States. Participants completed surveys at two different time points. The surveys included questions focused on measuring financial risk tolerance, subjective financial knowledge, objective financial knowledge, investment experience, cognitive reflection, and various demographic variables. Findings based on hierarchical partitioning models support the Domain‐Specificity Principle, which highlights how domain‐specific factors like subjective financial knowledge and investment experience are more predictive of financial risk tolerance than generalized characteristics such as education level or cognitive ability. Additionally, this study demonstrates the mediating effect of investment experience on the relationship between subjective financial knowledge and financial risk tolerance. In total, results underscore the importance of using domain‐specific investor characteristics rather than non‐specific attributes when studying financial decision‐making and the role of risk tolerance in describing investor outcomes.

ObjectiveTo provide a comprehensive review and analysis of guidelines from various professional and medical organisations regarding the use of prostate‐specific membrane antigen (PSMA) positron emission tomography (PET) as a staging scan for men with newly diagnosed intermediate‐risk prostate cancer (PCa).Materials and MethodsEnglish‐language guidelines and recommendations from the following associations and societies were reviewed and critically analysed: European Association of Urology (EAU), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), National Institute for Health and Care Excellence (NICE), Canadian Urological Association (CUA), American Society for Clinical Oncology (ASCO), Society for Nuclear Medicine and Medical Imaging (SNMMI).ResultsThere is significant disagreement among guidelines regarding whether PSMA PET is a useful staging tool for men with a new diagnosis of intermediate‐risk PCa. There is a stronger consensus that PSMA PET is useful in staging high‐risk PCa.ConclusionWhilst there is a growing body of evidence that supports the use of PSMA PET in newly diagnosed PCa, there is significant disagreement regarding its use for men with intermediate‐risk disease. Recommendations are generally weak and based on expert opinions. This is an area of considerable ongoing research, and guidelines are likely to change as new evidence emerges.

Active surveillance remains the preferred treatment for men with low-risk prostate cancer and select men with favourable intermediate-risk prostate cancer. It involves the close observation of clinicopathological parameters to assess for disease progression, aiming to delay or avoid definitive treatment and related toxicities for as long as possible, without compromising oncological outcomes. A recent advancement in prostate cancer staging is the PSMA PET scan, which uses a tracer that strongly binds a highly expressed cellular biomarker for prostate cancer. Recent articles have also demonstrated that PSMA PET may be a useful tool for risk-stratifying prostate cancer, with the SUVMax of the scan correlated with higher-grade prostate cancer. This has ignited interest in the potential use of PSMA PET to identify men with higher-risk prostate cancer who may be unsuitable for active surveillance, particularly those who were incorrectly classified as lower risk upon initial diagnosis. This review article aims to assess the current state of the literature and clinical guidelines regarding the use of PSMA PET as a tool to risk-stratify prostate cancer, and whether it can be incorporated into active surveillance protocols to identify men who were incorrectly risk-stratified at time of initial diagnosis.

We aim to determine the prognostic significance of glutathione S-transferase Pi 1 DNA methylation (mGSTP1) in two independent prostate cancer cohorts with long-term clinical follow-up data. We first re-examined a published, in-house whole genome bisulphite sequencing (WGBS) prostate cancer dataset, derived from radical prostatectomy (RP) tissue (n = 15) with median follow-up 19.5years, to confirm and visualise the association between mGSTP1 and patient mortality. To validate prognostic significance, we used a quantitative methylation-specific head-loop (MS-HL) assay to measure mGSTP1 levels in a larger, independent cohort (n = 186), and performed univariable and multivariable Cox survival analysis. Re-analysis of WGBS data showed a significant increase in mGSTP1 in RP samples from patients with lethal versus non-lethal disease. Subsequent analysis in the larger cohort using the MS-HL assay confirmed that mGSTP1 was detectable in 97% of RP samples, validating the diagnostic potential of mGSTP1. Univariable Cox survival analysis revealed a significant association between mGSTP1 levels and biochemical recurrence and metastatic relapse free survival, with a near-significant association with prostate cancer specific mortality. Notably, multivariable Cox models demonstrated that mGSTP1 did not add independent prognostic value beyond standard clinicopathological features. Our study supports the importance of DNA methylation as a tissue-based prostate tumour biomarker. GSTP1 methylation is well established as a diagnostic marker, and in this study, we find that GSTP1 methylation levels are also associated with disease prognosis. Further research is required into the clinical utility of prognostic methylation markers and their functional role in disease progression.