Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance.

Importance: Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.

Objective: To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.

Projected Outcomes of Reduced-Biopsy Management of Grade Group 1 Prostate Cancer: Implications for Relabeling.

Background: Implications of relabeling grade group (GG) 1 prostate cancer as non-cancer will depend on the recommended active surveillance (AS) strategy. Whether relabeling should prompt de-intensifying, PSA-based active monitoring approaches is unclear. We investigated outcomes of biopsy-based AS strategies vs PSA-based active monitoring for GG1 diagnoses under different patient adherence rates.

Validation of a prognostic blood-based sphingolipid panel for men with localized prostate cancer followed on active surveillance.

Background: We previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.

Methods: Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy.

Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer.

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making.

Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort.

Design, Setting, And Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008.

Exploring the relation of active surveillance schedules and prostate cancer mortality.

Background: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality.

High expression of Trop2 is associated with aggressive localized prostate cancer and is a candidate urinary biomarker.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study.

Constructing time-invariant dynamic surveillance rules for optimal monitoring schedules.

Dynamic surveillance rules (DSRs) are sequential surveillance decision rules informing monitoring schedules in clinical practice, which can adapt over time according to a patient's evolving characteristics. In many clinical applications, it is desirable to identify and implement optimal time-invariant DSRs, where the parameters indexing the decision rules are shared across different decision points. We propose a new criterion for DSRs that accounts for benefit-cost tradeoff during the course of disease surveillance.

Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN).

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS.

Dietary Patterns and Risk of Gleason Grade Progression among Men on Active Surveillance for Prostate Cancer: Results from the Canary Prostate Active Surveillance Study.

Modifiable lifestyle factors, such as following a healthy dietary pattern may delay or prevent prostate cancer (PCa) progression. However, few studies have evaluated whether following specific dietary patterns after PCa diagnosis impacts risk of disease progression among men with localized PCa managed by active surveillance (AS). 564 men enrolled in the Canary Prostate Active Surveillance Study, a protocol-driven AS study utilizing a pre-specified prostate-specific antigen monitoring and surveillance biopsy regimen, completed a food frequency questionnaire (FFQ) at enrollment and had ≥ 1 surveillance biopsy during follow-up.

Impact of Prostate Health Index Results for Prediction of Biopsy Grade Reclassification During Active Surveillance.

Purpose: We assessed whether Prostate Health Index results improve prediction of grade reclassification for men on active surveillance.

Methods And Materials: We identified men in Canary Prostate Active Surveillance Study with Grade Group 1 cancer. Outcome was grade reclassification to Grade Group 2+ cancer.

Divergent Effects of Ocean Warming On Byssal Attachment in Two Congener Mussel Species.

Organisms rely on the integrity of the structural materials they produce to maintain a broad range of processes, such as acquiring food, resisting predators or withstanding extreme environmental forces. The production and maintenance of these biomaterials, which are often modulated by environmental conditions, can therefore have important consequences for fitness in changing climates. One well-known example of such a biomaterial is mussel byssus, an array of collagen-like fibers (byssal threads) that tethers a bivalve mollusk securely to benthic marine substrates.

Reliability and Discriminant Validity of a Checklist for Surgical Scrubbing, Gowning and Gloving.

Background: Surgical scrubbing, gowning, and gloving is challenging for medical trainees to learn in the operating room environment. Currently, there are few reliable or valid tools to evaluate a trainee's ability to scrub, gown and glove. The objective of this study is to test the reliability and validity of a checklist that evaluates the technique of surgical scrubbing, gowning and gloving (SGG).

Germline mutations in penetrant cancer predisposition genes are rare in men with prostate cancer selecting active surveillance.

Background: Pathogenic germline mutations in several rare penetrant cancer predisposition genes are associated with an increased risk of aggressive prostate cancer (PC). Our objectives were to determine the prevalence of pathogenic germline mutations in men with low-risk PC on active surveillance, and assess whether pathogenic germline mutations associate with grade reclassification or adverse pathology, recurrence, or metastases, in men treated after initial surveillance.

Methods: Men prospectively enrolled in the Canary Prostate Active Surveillance Study (PASS) were retrospectively sampled for the study.

Conserved Targets to Prevent Emerging Coronaviruses.

Novel coronaviruses emerged as zoonotic outbreaks in humans in 2003 (SARS), 2012 (MERS), and notably in 2019 (SARS2), which resulted in the COVID-19 pandemic, causing worldwide health and economic disaster. Vaccines provide the best protection against disease but cannot be developed and engineered quickly enough to prevent emerging viruses, zoonotic outbreaks, and pandemics. Antivirals are the best first line of therapeutic defense against novel emerging viruses.

Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.

Background: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.

Methods: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium.

Analysis of separate training and validation radical prostatectomy cohorts identifies 0.25 mm diameter as an optimal definition for "large" cribriform prostatic adenocarcinoma.

Cribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests "large" cribriform glands associate with aggressive behavior; however, published studies use varying definitions for "large". We aimed to identify an outcome-based quantitative cut-off for "large" vs "small" cribriform glands.

Evaluating the Outcomes of Active Surveillance in Grade Group 2 Prostate Cancer: Prospective Results from the Canary PASS Cohort.

Purpose: Active surveillance (AS) for grade group (GG) 2 patients is not yet well defined. We sought to compare clinical outcomes of men with GG1 and GG2 prostate cancer undergoing AS in a large prospective North American cohort.

Materials And Methods: Participants were prospectively enrolled in an AS study with protocol-directed followup at 10 centers in the U.

Treatment in the absence of disease reclassification among men on active surveillance for prostate cancer.

Background: Maintaining men on active surveillance for prostate cancer can be challenging. Although most men who eventually undergo treatment have experienced clinical progression, a smaller subset elects treatment in the absence of disease reclassification. This study sought to understand factors associated with treatment in a large, contemporary, prospective cohort.

Effect of Diagnostic Biopsy Practice Location on Grade/Volume Reclassification in Active Surveillance for Prostate Cancer: A Multicenter Analysis from the Canary PASS Cohort.

Introduction: We analyzed the Canary Prostate Cancer Active Surveillance (PASS) cohort to determine if patients who had diagnostic biopsy at an off-site practice were at higher risk of reclassification than those having their diagnostic biopsy at a PASS site.

Methods: Participants were prospectively enrolled at 10 academic institutions. We included patients with Gleason score 6 at diagnostic biopsy, <34% positive cores and a first surveillance biopsy in a PASS site <2 years after diagnosis.