Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far.

Phage Biosensor for the Classification of Metastatic Urological Cancers from Urine.

Most of the annual 10 million cancer-related deaths are caused by metastatic disease. Survival rates for cancer are strongly dependent on the type of cancer and its stage at detection. Early detection remains a challenge due to the lack of reliable biomarkers and cost-efficient screening methods.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

Purpose: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen).

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important.

Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan.

Design, Setting, And Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020.

PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer.

Background And Objective: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty.

Methods: A panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology.

Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

Background: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade.

Study Design: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden.

Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS.

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment.

Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer.

BACKGROUND: EMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported. METHODS: In EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355).

Risk of Clinically Significant Prostate Cancer after a Nonsuspicious Prostate MRI-A Comparison with the General Population.

Background: We compare the risk of clinically significant (csPCa; ISUP Grade Group ≥ 2) and insignificant prostate cancer (isPCa; ISUP Grade Group 1) in men with a nonsuspicious prostate MRI (nMRI; PI-RADS ≤ 2) with the general population, and assess the value of PSA density (PSAD) in stratification.

Methods: In this retrospective population-based cohort study we identified 1,682 50-79-year-old men, who underwent nMRI at HUS (2016-2019). We compared their age-standardized incidence rates (IR) of csPCa and the odds of isPCa to a local age- and sex-matched general population (n = 230,458) during a six-year follow-up.

MRI-Targeted Prostate Biopsy Introduces Grade Inflation and Overtreatment.

Purpose: The use of MRI-targeted biopsies has led to lower detection of Gleason Grade Group 1 (GG1) prostate cancer and increased detection of GG2 disease. Although this finding is generally attributed to improved sensitivity and specificity of MRI for aggressive cancers, it might also be explained by grade inflation. Our objective was to determine the likelihood of definitive treatment and risk of post-treatment recurrence for patients with GG2 cancer diagnosed using targeted biopsies relative to men with GG1 cancer diagnosed using systematic biopsies.

Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial.

Introduction: Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening.

Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

Background: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown.

Methods: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less.

The impact of imputation quality on machine learning classifiers for datasets with missing values.

Background: Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete samples. The focus of the machine learning researcher is to optimise the classifier's performance.

Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis.

Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa-specific death (PCSD).

Capturing the Kidney Transcriptome by Urinary Extracellular Vesicles-From Pre-Analytical Obstacles to Biomarker Research.

Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of preanalytical choices hinder biomarker studies. We aimed to assess how preanalytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD)-linked miRNAs or kidney-linked miRNAs and mRNAs (kidney-RNAs) in uEV isolates and to discover stable reference mRNAs across diverse uEV datasets.

Genome-wide mRNA profiling in urinary extracellular vesicles reveals stress gene signature for diabetic kidney disease.

Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney-derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed ∼200 uEV mRNA samples from clinical studies by genome-wide sequencing to discover mechanisms and candidate biomarkers of diabetic kidney disease (DKD) in Type 1 diabetes (T1D) with replication in Type 1 and 2 diabetes. Sequencing reproducibly showed >10,000 mRNAs with similarity to kidney transcriptome.

Stromal FAP Expression is Associated with MRI Visibility and Patient Survival in Prostate Cancer.

Unlabelled: Some clinically significant prostate cancers are missed by MRI. We asked whether the tumor stroma in surgically treated localized prostate cancer lesions positive or negative with MRI are different in their cellular and molecular properties, and whether the differences are reflected to the clinical course of the disease. We profiled the stromal and immune cell composition of MRI-classified tumor lesions by applying multiplexed fluorescence IHC (mfIHC) and automated image analysis in a clinical cohort of 343 patients (cohort I).

Incidence of erectile dysfunction treatment after radical prostatectomy by Statin use in Finnish Nationwide Cohort Study.

Background: Erectile dysfunction (ED) is common after radical prostatectomy (RP) due to cavernous nerve damage. Risk of ED is also affected by vascular function. Statins prevent vascular events but their association with post-prostatectomy ED is unclear.

PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.

While organ-confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form of cell death initiated by cell detachment from the surrounding extracellular matrix, is one of the cellular processes critical for PCa progression towards aggressive disease. Therefore, further understanding of anoikis regulation in PCa might provide therapeutic opportunities.

Infectious complications after transrectal MRI-targeted and systematic prostate biopsy.

Purpose: To compare infectious complications after transrectal systematic prostate biopsy (SB) and magnetic resonance imaging (MRI)-targeted biopsy (TB) in a large retrospective cohort to assess whether one technique is superior to the other regarding infectious complications.

Methods: A total of 4497 patients underwent 5288 biopsies, 2875 (54%) SB and 2413 (46%) MRI-TB only. On average, 12 SB cores and 3.