Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers.

Advanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic).

External validation of a digital pathology-based multimodal artificial intelligence-derived prognostic model in patients with advanced prostate cancer starting long-term androgen deprivation therapy: a post-hoc ancillary biomarker study of four phase 3 randomised controlled trials of the STAMPEDE platform protocol.

Background: Effective prognostication improves selection of patients with prostate cancer for treatment combinations. We aimed to evaluate whether a previously developed multimodal artificial intelligence (MMAI) algorithm was prognostic in very advanced prostate cancer using data from four phase 3 trials of the STAMPEDE platform protocol.

Methods: We included patients starting androgen-deprivation therapy in the docetaxel, docetaxel plus zoledronic acid, abiraterone, or abiraterone plus enzalutamide trials.

Full fingerprint hyperspectral imaging of prostate cancer tissue microarrays within clinical timeframes using quantum cascade laser microscopy.

One of the major limitations for clinical applications of infrared spectroscopic imaging modalities is the acquisition time required to obtain reasonable images of tissues with high spatial resolution and good signal-to-noise ratio (SNR). The time to acquire a reasonable signal to noise spectroscopic scan of a standard microscope slide region of tissue can take many hours. As a trade-off, systems can allow for discrete wavenumber acquisitions, sacrificing potentially vital chemical bands in order to reach specific acquisition targets.

UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results.

Objective: Germline pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer.

Methods And Analysis: We reviewed germline/tumour DNA testing from 450 localised or metastatic prostate cancer cases in NW England mainly from 2022 to 2024.

Tale of two zones: investigating the clinical outcomes and research gaps in peripheral and transition zone prostate cancer through a systematic review and meta-analysis.

Objective: To assess pathological characteristics, clinical features and outcomes of patients diagnosed with peripheral zone (PZ) and transition zone (TZ) prostate cancer after prostatectomy.

Methods And Analysis: We systematically reviewed PubMed, EMBASE and MEDLINE. Primary endpoints were biochemical relapse-free survival (bRFS) and distant metastases rate; secondary endpoints included clinical and pathological features.

Non-steroidal anti-inflammatory drugs for treating symptomatic uncomplicated urinary tract infections in non-pregnant adult women.

Background: Almost half of all women will have at least one symptomatic urinary tract infection (UTI) in their lifetime. Although usually self-remitting, 74% of women contacting a health professional are prescribed an antibiotic, and in rare instances, they may progress to more severe infections. Therefore, the standard of care for the treatment of symptomatic uncomplicated UTIs is oral antibiotic therapy, which aims to achieve symptom resolution and prevent the development of complications such as pyelonephritis.

Management of Small Testicular Masses: A Delphi Consensus Study.

Background And Objective: The majority of small testicular masses (STMs) are benign and therefore radical orchidectomy (RO) may represent overtreatment. In appropriately selected patients, surveillance or testis-sparing surgery (TSS) is an alternative option to preserve testicular function. Since there are no clear guidelines, we aimed to develop consensus recommendations on the management of STMs.

Risk of Fractures and Falls in Men with Advanced or Metastatic Prostate Cancer Receiving Androgen Deprivation Therapy and Treated with Novel Androgen Receptor Signalling Inhibitors: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

Context: The addition of androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) has improved survival outcomes in patients with advanced prostate cancer (PCa). Advanced PCa patients have a higher incidence of osteoporosis, compounded by rapid bone density loss upon commencement of ADT resulting in an increased fracture risk. The effect of treatment intensification with ARSIs on fall and fracture risk is unclear.

Systematic Review and Meta-analysis of Minimally Invasive Procedures for Surgical Inguinal Nodal Staging in Penile Carcinoma.

Context: There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma.

Objective: To evaluate the diagnostic accuracy, perioperative outcomes, and complications of minimally invasive surgical procedures for nodal staging in penile carcinoma.

Evidence Acquisition: A systematic review of the Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.

Point-of-Care Prostate Specific Antigen Testing: Examining Translational Progress toward Clinical Implementation.

Prostate cancer (PCa) is the second most common male cancer and is attributable to over 375,000 deaths annually. Prostate specific antigen (PSA) is a key biomarker for PCa and therefore measuring patient PSA levels is an important aspect of the diagnostic pathway. Automated immunoassays are currently utilized for PSA analysis, but they require a laboratory setting with specialized equipment and trained personnel.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

Purpose: Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis.

Material And Methods: This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

Context: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease.

Objective: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer.

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol.

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.

Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland.

European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update.

Context: Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines.

Objective: To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer.

Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial.

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2×10) and identified clinically-relevant differences in absolute benefit, especially for localized cancers.

Spatial and molecular profiling of the mononuclear phagocyte network in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSCs) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes.

Integration of High-Throughput Imaging and Multiparametric Metabolic Profiling Reveals a Mitochondrial Mechanism of Tenofovir Toxicity.

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic complications. The antiviral drug tenofovir disoproxil fumarate (TDF) is an archetypal nephrotoxin, inducing mitochondrial abnormalities and urinary solute wasting, for reasons that were previously unclear.

Non-canonical EphA2 activation underpins PTEN-mediated metastatic migration and poor clinical outcome in prostate cancer.

Background: The key process of mesenchymal to amoeboid transition (MAT), which enables prostate cancer (PCa) transendothelial migration and subsequent development of metastases in red bone marrow stroma, is driven by phosphorylation of EphA2 by pAkt, which is induced by the omega-6 polyunsaturated fatty acid arachidonic acid. Here we investigate the influence of EphA2 signalling in PCa progression and long-term survival.

Methods: The mechanisms underpinning metastatic biopotential of altered EphA2 signalling in relation to PTEN status were assessed in vitro using canonical (EphA2) and non-canonical (EphA2) PC3-M mutants, interrogation of publicly available PTEN-stratified databases and clinical validation using a PCa TMA (n = 177) with long-term follow-up data.

Automated quantitative high-throughput multiplex immunofluorescence pipeline to evaluate OXPHOS defects in formalin-fixed human prostate tissue.

Advances in multiplex immunofluorescence (mIF) and digital image analysis has enabled simultaneous assessment of protein defects in electron transport chain components. However, current manual methodology is time consuming and labour intensive. Therefore, we developed an automated high-throughput mIF workflow for quantitative single-cell level assessment of formalin fixed paraffin embedded tissue (FFPE), leveraging tyramide signal amplification on a Ventana Ultra platform coupled with automated multispectral imaging on a Vectra 3 platform.

Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson's disease.

Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson's disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson's disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson's disease, mitochondrial disease, and control cases.