Stockholm3 Validation Study in a Multi-Ethnic Cohort

NCT04583072 | Completed DMC

• 1 other identifier: KarolinskaI3
• Study Type: observational
• Target: 2,152
• Locations: 2 countries
• Sites: 14

Brief Summary

Introduction: Prostate cancer (PCa) is the most commonly detected cancer in men and is the second leading cause of cancer death. Differences in race and ethnicity have been shown to have differences in PCa incidence, detection, and outcomes. Current prostate cancer screening involves prostatic specific antigen (PSA) which is a nonspecific protein marker (aka kallikrein) that can often leads to unnecessary biopsies (up to 74% benign biopsies) and clinical overdiagnosis (with up to 22% clinically insignificant cancer). Recently more sophisticated tests have been developed for PCa screening in the United States such as the Prostate Health Index (PHI) and the 4k (kallikrein) score, as well as clinical models that use information from the patient clinical history. However, these tests utilize limited serum protein assays and none of the established screening protocols utilize genetic variables to help account for the likely inherited risks as seen in different ethnicities. A recent Swedish, prospective, population-based study, published in the Lancet Oncology, developed a unique multivariable biopsy outcome prediction model within a Nordic population of nearly 60,000 men. This model, the Stockholm3, which incorporated plasma protein markers, germline DNA SNPs as well as clinical variables, was shown to be capable of reducing the number of biopsies by 44% compared to PSA while maintaining adequate sensitivity for detection of PCa. It is unknown whether an approach developed in Sweden that incorporates protein markers, genetics, clinical variables, and genetic ancestry would be beneficial in a racially diverse cohort. Hypothesis: The investigators hypothesize that, a prospectively studied multiethnic cohort of men with the Stockholm3 test will identify unique and common risk factors that improve prostate cancer detection. Aim: To assess the performance of the Stockholm3 test as compared to PSA and to identify unique features associated with PCa in Black/African American (n=500), Asian (n=500), White/Caucasian Hispanic (n=500), and White/Caucasian Non-Hispanic (n=500) men. Methods: The investigators propose a prospectively identified cohort with participating institutions which have screened positive to undergo a prostate biopsy to have a retrospective analysis the Stockholm3 test and ancestry markers. Within this cohort the investigators will examine several predetermined risk factors to investigate their relationship to prostate cancer. This blood sample will be tested for quantitative levels of serum protein markers and DNA will be extracted and will be tested for germline mutations as defined by the Stockholm3 test and other ancestry informative markers. Results from the study will be presented in such a way that no individual information will be disclosed.

Conditions

Prostate Cancer (Diagnosis)

Outcome Measures

Primary Outcomes (1)

• Gleason Grade Group 2 Prostate Cancer

  International Society of Urological Pathology Gleason Grade Group 2 Prostate Cancer. Gleason Grade Group scale is used to grade prostate cancer if found on a scale from 1 to 5. A higher score means a worse outcome.

  On prostate biopsy immediately following PSA

Secondary Outcomes (1)

• National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk prostate cancer or higher risk

  On prostate biopsy immediately following PSA

Study Arms (4)

Non-Hispanic/Latino White/Caucasian men

Self-identified as White Non-Hispanic men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer

Diagnostic Test: The Stockholm3 test

African/Black men

Self-identified as African or Black men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer

Diagnostic Test: The Stockholm3 test

Hispanic/Latino White/Caucasian men

Self-identified as White Hispanic men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer

Diagnostic Test: The Stockholm3 test

Asian men

Self-identified as Asian men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer

Diagnostic Test: The Stockholm3 test

Interventions

The Stockholm3 test DIAGNOSTIC_TEST

Venipuncture: Prior to the biopsy the blood will be collected in 2 EDTA (lavender top) x 4 ml tubes will be removed after obtaining consent from the subjects.

Also known as: Diagnostic Test: Custom ancestry informative genetic markers

African/Black men; Asian men; Hispanic/Latino White/Caucasian men; Non-Hispanic/Latino White/Caucasian men

Eligibility Criteria

• Age: 45 Years - 75 Years
• Gender Eligibility Details: Biologic XY sex
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The subjects will be consented for prostate biopsy as part of standard of care. No additional advertising will be used for enrollment. Patients will be identified in clinic which meet the above inclusion criteria for prostate biopsy as part of routine practice. Enrollment will start from date of IRB approval and continue until study enrollment goal. Study enrollment goal will be 2,000 men who have a self-described race/ethnicity of: African/Black (n=500), Asian (n=500), Hispanic White/Caucasian (n=500), and Non-Hispanic White/Caucasian (n=500) men.

You may qualify if:

• All men (age 45.0 - 75.0 years), regardless of race, presenting to a practicing urologist with symptoms that would lead to an evaluation for prostate cancer and who are scheduled to receive a needle biopsy of the prostate
• No prior diagnosis of prostate cancer

You may not qualify if:

• Men who in the three (3) months prior to study participation received any invasive urologic procedure such as biopsy, thermotherapy, microwave therapy, laser therapy, transurethral resection of the prostate (TURP), urethral catheterization, and lower genitourinary tract endoscopy (cystoscopy)
• Men who were subjected to DRE or prostate manipulation within five (5) days (120 hours) prior to blood sampling

Sponsors & Collaborators

• Karolinska Institutet: lead
• University of Illinois at Chicago: collaborator
• UroPartners: collaborator
• University of Chicago: collaborator
• Rush University Medical Center: collaborator
• Montefiore Medical Center: collaborator
• The University of Texas Health Science Center at San Antonio: collaborator
• Cook County Health & Hospitals System: collaborator
• Cook County Health: collaborator
• Stanford University: collaborator
• Northwestern Medicine: collaborator
• University of Southern California: collaborator
• University Health Network, Toronto: collaborator
• Urology Clinics of North Texas: collaborator
• LAC+USC Medical Center: collaborator

Study Sites (14)

Los Angeles County

Los Angeles, California, 90033, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Cook County Health System

Chicago, Illinois, 60615, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Uropartners

Westchester, Illinois, 60154, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Urology Clinics of North Texas

Dallas, Texas, 75231, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

University Health Network

Toronto, Ontario, Canada

Location

Related Publications (18)

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  PMID: 39038251 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Venipuncture: Prior to the biopsy the blood will be collected in 2 EDTA (lavender top) x 4 milliliters (8 milliliters total) tubes will be removed after obtaining consent from the subjects. One tube will be immediately centrifuged (10 minutes at 2000G) and plasma decanted to a tube without additives (this typically produces approximately 1.5 milliliters of plasma). The decanted tube (with plasma) and the remaining EDTA tube (with whole blood) is then frozen and stored at -20 degrees Celsius until being shipped to the A3P lab for Stockholm3 testing and analysis at -20 degrees Celsius (unless processing for DNA extraction and plasma analysis). Other biobanked specimens (as described in the Study detailed description) will be collected prospectively and will include plasma and Buffy Coat (used for DNA extraction) utilising the study inclusion and exclusion criteria.

MeSH Terms

Conditions

Prostatic Neoplasms; Disease

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henrik Grönberg, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 12, 2020
• Study Start: December 15, 2019
• Primary Completion: July 15, 2023
• Study Completion: July 15, 2023
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (13)