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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. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy 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. Methods: Two 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. Results: A 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. Conclusions: In 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 FROM AUTHOR]

PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described. METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley's databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed. RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P =.04) and poorer overall survival (28 v 45 months, P =.04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences. CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes. Drug-drug interactions between conmeds and ENZ or AA were common and impacted outcomes in #ePAD real-world mCRPC pts. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen positron emission tomography-computed tomography use prior to systemic therapy in metastatic castration-resistant prostate cancer Abbreviations (m)CRPC (metastatic) castration-resistant prostate cancer ePAD electronic Prostate Cancer Australian Database FDG fluorodeoxyglucose HSPC hormone-sensitive prostate cancer LN lymph nodes PET positron emission tomography PSMA prostate-specific membrane antigen WBBS whole-body bone scan Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-CT imaging has demonstrated greater sensitivity compared to conventional imaging modalities with CT and whole-body bone scan (WBBS) in the detection of metastatic prostate cancer [[1]]. A further 15 patients (17%) had dedicated CT alone in addition to PSMA PET-CT, while eight (9%) had additional WBBS alone in addition to PSMA PET-CT (Fig. [Extracted from the article]

Health economic outcomes of real-world treatment sequencing of androgen receptor-targeted agents (ARTA) and docetaxel (DOC) remain unclear. Data from the electronic Castration-resistant Prostate cancer Australian Database (ePAD) were analyzed including median overall survival (mOS) and median time-to-treatment failure (mTTF). Mean total costs (mTC) and incremental cost-effectiveness ratios (ICER) of treatment sequences were estimated using the average sample method and Zhao and Tian estimator. Of 752 men, 441 received ARTA, 194 DOC, and 175 both sequentially. Of participants treated with both, first-line DOC followed by ARTA was the more common sequence (n = 125, 71%). mOS for first-line ARTA was 8.38 years (95% CI: 3.48, not-estimated) vs. 3.29 years (95% CI: 2.92, 4.02) for DOC. mTTF was 15.7 months (95% CI: 14.2, 23.7) for the ARTA-DOC sequence and 18.2 months (95% CI: 16.2, 23.2) for DOC-ARTA. In first-line, ARTA cost an additional $13,244 per mTTF month compared to DOC. In second-line, ARTA cost $6726 per mTTF month. The DOC-ARTA sequence saved $2139 per mTTF compared to ARTA-DOC, though not statistically significant. ICERs show ARTA had improved clinical benefit compared to DOC but at higher cost. There were no significant cost differences between combined sequences. [ABSTRACT FROM AUTHOR]

Aims: Multiple life‐prolonging therapies are available for metastatic castration‐resistant prostate cancer (mCRPC). However, the optimal treatment strategy following progression through standard treatment with docetaxel, androgen receptor signaling inhibitor (ARSI) and cabazitaxel, remains unclear. We aimed to describe treatment patterns in men with mCRPC following progression on standard treatments and determine whether subsequent treatment choice impacts overall survival. Methods: Clinicopathologic and treatment data were extracted from the electronic CRPC Australian Database (ePAD) for patients who had received docetaxel, ARSIs and cabazitaxel in any order. Data were analyzed to compare groups that did versus did not receive subsequent systemic therapy. Treatment sequences, median duration of treatment, and median overall survival (mOS) were reported for each treatment group. Results: Ninety‐eight eligible patients were identified, with 51 receiving subsequent systemic therapy. Those who received further treatment were younger (68 vs. 71 years, p <.01) but did not have any other differences in clinicopathologic features compared to those who received no further treatment. Patients who received upfront docetaxel were more likely to proceed to subsequent treatment (p =.02). Subsequent systemic therapies varied, the most common being carboplatin‐based regimens (n = 13, 25.5%) and many patients were rechallenged with ARSI (n = 10, 19.6%) or docetaxel (n = 6, 11.8%). There was no difference in mOS according to subsequent systemic therapy (p =.09). Conclusion: This retrospective multicenter analysis demonstrates the variation in treatment sequences used for mCRPC in the real‐world setting. In the absence of high quality, prospective evidence, our results suggest that subsequent treatment choice does not influence survival outcomes and the optimal choice is guided by individual patient and disease‐related factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Registry data has the potential to support a broad range of research, audit and education initiatives. Here, we describe the experience and learnings of a series of large multi-institutional cancer registries that leverage real-world clinical data for a range of purposes, that informs the conduct and output of each registry in a virtuous cycle. Lessons learnt include the need for careful and continuous curation of information being collected, regular database updates, and the need for a continued focus on data quality. As a standalone resource, each registry has supported numerous projects, but linkage with external datasets with patients in common has enhanced the research potential. Multiple projects have linked registry data with matched tissue specimens to support the discovery and valiation of prognostic and predictive markers in the tumour and blood specimens. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly studies exploring the best use of drug options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data. Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data. [ABSTRACT FROM AUTHOR]

The authors comment on a study by N. Sayegh and colleagues published within the issue which highlighted the advances in the therapeutic armamentarium of advanced prostate cancer. Topics include importance of addressing the barriers to treatment access in the global management of metastatic prostate cancer, importance of the role of multidisciplinary team in ensuring a holistic approach to overall patient care, and role of specialist nurses in support patients.

Objectives: To investigate the recent real‐world use of first‐generation antiandrogens (FGAs) in metastatic castration‐resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study. Patients and Methods: The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan–Meier method and groups compared using log‐rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model. Results: We identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow‐up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre‐treatment prostate‐specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life‐prolonging treatments for mCRPC or their PSA50 response rates. Conclusion: In our present cohort, FGAs were commonly used in lower‐risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS. [ABSTRACT FROM AUTHOR]

Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first‐line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2‐amplified breast cancer (BC) and castrate‐resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice‐changing trial. Registry patients were older than the matched trial cohort by a median of 2‐6 years (all P = <.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0‐1 patients was lower for CRC (94.1% vs 99.2%, P =.001) and BC (94.9% vs 99.3%, P =.001). Progression‐free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, Hazard Ratio [HR] = 0.65, P = <.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, P = <.001). In conclusion, despite real‐world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased postprogression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans. What's new? Clinical trials have strict eligibility criteria, potentially limiting external validity, but the issue has seldom been explored in studies. Here, the authors examine data from a series of advanced cancer registries, confirming previous findings that trial patients are younger and fitter than consecutive routine care patients. However, the data show that real‐world patients can have survival outcomes that match or exceed those reported in trials. The authors further explore why real‐world outcomes may improve after a new therapy becomes standard of care and how the potential for survival gains over time should be routinely factored into future trial statistical plans. [ABSTRACT FROM AUTHOR]

Aim: Optimal treatment for newly diagnosed metastatic hormone‐sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D‐ADT). This study sought to define the therapy used and associated activity following D‐ADT. Methods: Retrospective analysis of patients with mHSPC treated with one or more cycles of D‐ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first‐line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate‐specific antigen (PSA) reduction >50% and time from 1L to second‐line (2L) treatment initiation. Results: A total of 93 patients received D‐ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9–16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9–7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second‐line treatment was 7.3 months (1.3–27.4), which did not differ significantly between treatment groups. Conclusions: Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D‐ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D‐ADT needed. [ABSTRACT FROM AUTHOR]

Background: The impact of regulatory approvals of new therapies for castration‐resistant prostate cancer (CRPC) in Australia is unclear. Aims: To determine if changes in novel therapy access in Australia affected how clinicians initially managed men with newly diagnosed CRPC. Methods: Data from patients diagnosed with CRPC from 2013 to 2016 across three Australian hospitals were retrospectively collected. Baseline clinicopathological factors and initial management decision at the time of CRPC development (early treatment (ET) vs deferred treatment (DT)) were recorded. Categorical variables between cohorts were compared by Chi‐squared analysis. Cox regression analysis was performed to assess the impact of CRPC diagnosis year on time to commencing life‐prolonging systemic treatment (TTT). Results: Our study identified 137 CRPC patients, with 126 (92%) patients receiving life‐prolonging systemic treatment. The median age was 73 years. The initial management decision was DT in 71 (52%) patients and ET in 66 (48%) patients. There was a significant shift from DT to ET during the study period (2013–2014: DT 61% vs ET 33%; 2015–2016: DT 39% vs ET 67%; P = 0.004), with a rise in novel androgen receptor signalling inhibitor use and simultaneous reduction in first‐generation antiandrogen use at CRPC development. Each successive CRPC diagnosis year was associated with shorter TTT on univariate analysis (HR: 1.5, 95% CI: 1.3–1.7, P < 0.001). Conclusion: Over time, clinicians are favouring earlier introduction of life‐prolonging systemic treatment at the development of CRPC. This trend is largely driven by substantial uptake of novel androgen receptor signalling inhibitors as the preferred initial treatment for CRPC patients. [ABSTRACT FROM AUTHOR]

Aim: 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. Method: Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusion International practice guidelines recommend administration of bone‐modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal‐related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear.To describe real‐world practice of Australian breast oncologists.Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)‐Positive Australian Patient (TABITHA), a multi‐site Australian HER2+ MBC registry.Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32–87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first‐line systemic anti‐HER2 therapy (95% vs 83%; P = 0.04), to present with bone‐only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4‐weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data.Three‐quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence. [ABSTRACT FROM AUTHOR]

Background: Distress 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., Objective: We evaluated a web-based intervention, Nuts & Bolts, designed to provide support and alleviate distress after diagnosis of testicular cancer., Methods: Using 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., Results: Overall, 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<.001). Median DT, HADS-Anxiety, and HADS-Depression scores reduced between orchidectomy and 3 weeks postoperatively and then remained stable throughout the observation period. Thematic analysis of 16 semistructured interviews revealed 4 key themes, "Nuts & Bolts is a helpful tool," "Maximizing benefits of the website," "Whirlwind of diagnosis and readiness for treatment," and "Primary stressors and worries," as well as multiple subthemes., Conclusions: Distress is common following the diagnosis of testicular cancer; however, it decreases over time. Nuts & Bolts was considered useful, acceptable, and relevant by individuals diagnosed with testicular cancer, with strong support for the intervention rendered by thematic analyses of semistructured interviews. The best time to introduce support, such as Nuts & Bolts, is yet to be determined; however, it may be most beneficial as soon as testicular cancer is strongly suspected or diagnosed., (©Ciara Conduit, Christina Guo, Allan B Smith, Orlando Rincones, Olivia Baenziger, Benjamin Thomas, Jeremy Goad, Dan Lenaghan, Nathan Lawrentschuk, Lih-Ming Wong, Niall M Corcoran, Margaret Ross, Peter Gibbs, Sophie O'Haire, Angelyn Anton, Elizabeth Liow, Jeremy Lewin, Ben Tran. Originally published in JMIR Cancer (https://cancer.jmir.org), 28.10.2022.)

Background: Despite the rapidly evolving therapeutic landscape, immunotherapy has demonstrated limited activity in prostate cancer. A greater understanding of the molecular landscape, particularly the expression of immune-related pathways, will inform future immunotherapeutic strategies. Consensus nonnegative matrix factorization (cNMF) is a novel model of molecular classification analyzing gene expression data, focusing on biological interpretation of metagenes and selecting meaningful clusters., Objective: We aimed to identify molecular subtypes of prostate cancer using cNMF and correlate these with existing biomarkers to inform future immunotherapeutic strategies., Methods: A cohort of archival tumor specimens from hormone-sensitive and castration-resistant disease was studied. Whole transcriptomic profiles were generated using TruSeq RNA Access technology and subjected to cNMF. Comprehensive genomic profiling was performed with the FoundationOne assay. NMF subtypes were characterized by gene expression pathways, genomic alterations and correlated with clinical data, then applied to The Cancer Genome Atlas data set., Results: We studied 164 specimens, including 52 castration-resistant and 13 paired primary/metastatic specimens. cNMF identified four distinct subtypes. NMF1 (19%) is enriched for immune-related and stromal-related pathways with transforming growth factor β (TGFβ) signature. NMF2 (36%) is associated with FOXO-mediated transcription signature and AKT signaling, NMF3 (26%) is enriched for ribosomal RNA processing, while NMF4 (19%) is enriched for cell cycle and DNA-repair pathways. The most common gene alterations included TMPRSS22 (42%), TP53 (23%), and DNA-repair genes (19%), occurring across all subtypes. NMF4 is significantly enriched for MYC and Wnt-signaling gene alterations. TMB, CD8 density, and PD-L1 expression were low overall. NMF1 and NMF4 were NMF2 was associated with superior overall survival., Conclusions: Using cNMF, we identified four molecularly distinct subtypes which may inform treatment selection. NMF1 demonstrates the most inflammatory signature with asuppressive TGFβ signature, suggesting potential benefit with immunotherapy combination strategies targeting TGFβ and PD-(L)1. Prospective studies are required to evaluate the use of this novel model to molecularly stratify patients for optimal treatment selection., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

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  < 0.0001). Median TTF was significantly higher in those receiving ENZ (12.4 months) and AA (11.9 months) compared to DOC (8.3 months, p  < 0.001). PSA50 response rates and OS were not statistically different. Time to developing CRPC > 12 months was independently associated with longer TTF (HR 0.67, p  < 0.001) and OS (HR 0.49, p  = 0.002)., Conclusion: In our real-world population, ENZ and AA were common first-line systemic therapy choices, particularly among older patients and those with poorer performance status. Patients receiving ENZ and AA demonstrated superior TTF compared to DOC, while OS was not statistically different. Our findings highlight the important role of ARSIs, given the variability of access worldwide., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)