Abbreviated Name

URS Reference Set App: Boutros (2020)

Lead Investigator

Boutros, Paul — The University of California, Los Angeles

Coordinating Investigator

Zheng, Yingye — Fred Hutchinson Cancer Center

Involved Investigators

• Boutros, Paul — The University of California, Los Angeles
• Srivastava, Sudhir — National Cancer Institute
• Zheng, Yingye — Fred Hutchinson Cancer Center

Abstract

Same as Objectives

Aims

Aim 1: Collect tissue, blood, and urine specimens to obtain 195 complete specimen sets under the URS protocol. We have recruited 146 complete sample sets with updated SOPs suitable for biomarker validation studies. An additional 74 subjects have been recruited under the SOPs but Based on historical completion and eligibility rates for recruited subjects, we estimate 186 complete sample sets will be in-hand when these subjects complete treatment (Table 1 below). We are seeking support to gather these in-queue specimens and to recruit an additional 30 subjects to ensure we have a large enoughcomplete sample set to evaluate candidate biomarkers, both those developed within the EDRN and by the broader scientific community. Aim 2: Perform Germline whole-genome sequencing for each subject in the cohort to validate the PRS markers with respect to upgrading as previously reported. Our second aim will attempt to validate an established PRS and assess its ability to predict upgrading. This will simultaneously create a resource to enrich the characterization of the cohort for all future studies and enable low-cost validation of any future germline-based risk markers

Analytic Method

For validation, the primary null hypothesis is H0: ROC-1(0.98) ≥ 0.98 for lower threshold and the secondary hypothesis is H0: ROC (0.02) ≤0.25 for higher threshold. If the true false positive rate, ROC-1(0.98) ≤ 0.65 using this threshold, the study will have 90% power if we have 195 biopsy GS=6 patients. We will use the final study sample of n=240 to account for various factors (lower than 60% upgrading rate, inadequate biospecimen for assay, missing radical prostatectomy outcome). The power calculation used the formula for testing ROC-1(p) in [Pepe]. Assuming 60% upgrading prevalence, 35% specificity at threshold corresponding to 98% sensitivity leads to NPV=92.1%, judged adequate for patients with GS=3+3 to avoid radical prostatectomy and adopt active surveillance. Of particular interest are the comparisons of the performance of clinical predictors alone, and clinical predictors combined with blood, urine, or tumor-tissue based biomarkers.

Outcome

The majority of men with low-risk prostate cancer are currently being managed on active surveillance. Nonetheless, many of these men ultimately elect to undergo additional therapy (e.g., surgery or radiation therapy) because of concerns that they have more aggressive disease than was detected by biopsy. This concern is based on previous studies demonstrating that a significant number of patients who undergo radical prostatectomies indeed have higher grade disease than originally diagnosed, which represents an upgrading of their risk status. The lack of robust biomarkers to predict the presence of aggressive prostate cancer in this clinical setting contribute to the ongoing over-treatment of low-grade localized prostate cancer. To assist in counseling these men, the EDRN GU working group began gathering a cohort of men with low grade disease (Defined as Gleason 6), who ultimately chose to have a prostatectomy. The goal was to identify pre-therapeutic biomarkers that could predict upgrading. These biological specimens comprise the Upgrading Reference Set (URS), and have been gathering using EDRN core funds.

Publications

• No publications available at this time for this protocol.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

• Upgrading Reference Set WGS Sequencing

 Team Project

Start Date

Apr 1 2020

Estimated Finish Date

Mar 31 2021

Finish Date

Jun 15 2023

Protocol ID

464

Protocol Type

Reference Set

Fields of Research

• Genomics

Collaborative Group

Prostate and Urologic Cancers Research Group

Cancer Types

• Malignant neoplasm of prostate

Phased Status

1