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Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population. An analysis of the first 753 metastatic castration-resistant prostate cancer (mCRPC) patients within ePAD demonstrated that 43% were aged 75 years and older. Older patients were more likely to have comorbidities including ischemic heart disease, diabetes and previous stroke. Treatment outcomes were similar in all age groups. However, older patients receiving chemotherapy were more likely to stop treatment due to toxicity. Furthermore, in a smaller ePAD analysis involving additional chart reviews within 3 high volume centres, at least one relative or absolute contraindication to abiraterone was seen in 72% of our cohort and with enzalutamide in 14%. In total, 47% had potential clinically significant drug interactions with abiraterone and 67% with enzalutamide. Registry-based randomised controlled trials (RRCTs) are a novel trial methodology aiming to bridge the gap between retrospective registry analyses and traditional randomised controlled trials. We conducted the REAL-Pro study in advanced prostate cancer, comparing cognition, depression and falls risk between CRPC patients receiving abiraterone or enzalutamide. The study closed early due to slow recruitment and a changing treatment landscape, highlighting the need for further research to understand clinician and patient perspectives towards pragmatic trials such as RRCTs and subsequently develop strategies to optimise future trial design and recruitment.

BackgroundImmunotherapy has demonstrated limited activity in prostate cancer to date. This likely reflects an immune suppressive tumor microenvironment (TME), with previous studies suggesting low PD-L1 expression and a sparse immune cell infiltrate. We aimed to further characterise the immune TME in primary prostate cancer and correlate immune subset densities with clinical outcomes.MethodsTwo distinct cohorts of patients treated with radical prostatectomy were identified, based on the development of biochemical recurrence (BCR), one subgroup with high International Society of Urological Pathologists (ISUP) grade group, recurrent disease and a second with low grade, non-recurrent disease. A prostate immunohistochemical (IHC) antibody cocktail was used to differentiate tumor and peritumoral benign tissue. Specific CD8+, CD4+, FoxP3+, CD20+ and CD68+ cell subsets were identified using IHC staining of consecutive slides. PD-L1 and CD8/PD-L1 dual staining were also performed. Cell subset densities were quantified within tumor and peritumoral regions. We used descriptive statistics to report cell subset densities and T-tests to compare groups by age, grade and the development of BCR. Univariable and multivariable logistic regression were used to analyse risk factors for BCR and the development of metastatic disease.ResultsA total of 175 patients were included, with a median age of 63 years and median pre-operative PSA of 8.2ng/ml. BCR occurred in 115 patients (66%) and 56 (32%) developed metastatic disease. CD68+ cells were the most abundant (median 648.8/mm2 intratumoral, 247.6/mm2 peritumoral), while PD-L1+ and PD-L1/CD8+ cell density was low overall (PD-L1+ median 162.4/mm2 intratumoral, 141.7/mm2 peritumoral; PD-L1/CD8+ (median 5.52/mm2 intratumoral, 3.41/mm2 peritumoral). Overall, grade group and T-stage were independently associated with BCR and metastatic disease. Higher density of peritumoral PD-L1+ cells was an independent risk factor for BCR (OR 5.33, 95%CI 1.31-21.61, p = 0.019).Although higher densities of CD8+ and CD4+ cells were observed in higher grade group 3-5 tumors, these were not associated with the development of BCR or metastasis.ConclusionsIn our cohort of prostate cancer patients who underwent radical prostatectomy, higher grade group and T-stage were independent predictors of BCR and metastasis. Despite higher grade group being associated with higher CD8+ cell density, PD-L1+ and PD-L1/CD8+ cell densities were low overall, suggesting lower T cell receptor recognition of tumor antigens. Further understanding of this phenomenon would influence development of future immunotherapeutic strategies in prostate cancer.

Abstract Introduction Several systemic therapies have demonstrated a survival advantage in metastatic castration resistant prostate cancer (mCRPC). Access to these medications varies significantly worldwide. In Australia until recently, patients must have received docetaxel first, unless unsuitable for chemotherapy, despite no evidence suggesting superiority over androgen receptor signalling inhibitors (ARSIs). Our study investigated real‐world systemic treatment patterns in Australian patients with mCRPC. Methods The electronic CRPC Australian Database (ePAD) was interrogated to identify mCRPC patients. Clinicopathological features, treatment and outcome data, stratified by first‐line systemic therapies, were extracted. Comparisons between groups utilised Kruskal–Wallis tests and Chi‐Square analyses. Time‐to‐event data were calculated using Kaplan–Meier methods and groups compared using log‐rank tests. Factors influencing overall survival (OS) and time to treatment failure (TTF) were analysed through Cox proportional hazards regression models. Results We identified 578 patients who received first‐line systemic therapy for mCRPC. Enzalutamide (ENZ) was most commonly prescribed (n = 240, 41%), followed by docetaxel (DOC, n = 164, 28%) and abiraterone (AA, n = 100, 17%). Patients receiving ENZ or AA were older (79, 78.5 years respectively) compared with DOC (71 years, p = 0.001) and less likely to have ECOG performance status 0 (45%, 44%, 59% in ENZ, AA and DOC groups respectively p 12 months was independently associated with longer TTF (HR 0.67, p

BackgroundDistress is common immediately after diagnosis of testicular cancer. It has historically been difficult to engage people in care models to alleviate distress because of complex factors, including differential coping strategies and influences of social gender norms. Existing support specifically focuses on long-term survivors of testicular cancer, leaving an unmet need for age-appropriate and sex-sensitized support for individuals with distress shortly after diagnosis. ObjectiveWe evaluated a web-based intervention, Nuts & Bolts, designed to provide support and alleviate distress after diagnosis of testicular cancer. MethodsUsing a mixed methods design to evaluate the acceptability, feasibility, and impact of Nuts & Bolts on distress, we randomly assigned participants with recently diagnosed testicular cancer (1:1) access to Nuts & Bolts at the time of consent (early) or alternatively, 1 week later (day 8; delayed). Participants completed serial questionnaires across a 4- to 5-week period to evaluate levels of distress (measured by the National Comprehensive Cancer Network Distress Thermometer [DT]; scored 0-10), anxiety, and depression (Hospital Anxiety and Depression Score [HADS]–Anxiety and HADS-Depression; each scored 0-21). The primary end point was change in distress between consent and day 8. Secondary end points of distress, anxiety, and depression were assessed at defined intervals during follow-up. Optional, semistructured interviews occurring after completion of quantitative assessments were thematically analyzed. ResultsOverall, 39 participants were enrolled in this study. The median time from orchidectomy to study consent was 14.8 (range 3-62) days. Moderate or high levels of distress evaluated using DT were reported in 58% (23/39) of participants at consent and reduced to 13% (5/38) after 1 week of observation. Early intervention with Nuts & Bolts did not significantly decrease the mean DT score by day 8 compared with delayed intervention (early: 4.56-2.74 vs delayed: 4.47-2.74; P=.85), who did not yet have access to the website. A higher baseline DT score was significantly predictive of reduction in DT score during this period (P

To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000), triglycerides (P = .050), low density lipoprotein (P = .009) and non-fasting blood glucose (15 min) (P = .024) were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC). Non-fasting insulin in South Asians (15-120 min), in South East/East Asians (60-120 min), and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006). The molar ratio of C-peptide AUC/Insulin AUC (P = .045) and adiponectin (P = .037) were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022) and rs10830963 (P = 0.009), which are both near the melatonin receptor MTNR1B.Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.