Prostate Cancer (Diagnosis)SEPTANCT04583072
Stockholm3 Validation Study in a Multi-Ethnic Cohort
An observational study of Prostate Cancer (Diagnosis), run by Karolinska Institutet at 14 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 75 years, men only
- Conditions the study is for
- Prostate Cancer (Diagnosis)
- What is being tested?
- The Stockholm3 test
- How many people
- 2,152 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 15 Dec 2019to 15 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- Men only
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States13 sites
Northwestern Medicine
Chicago, Illinois, 60611
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois, 60612
Rush University Medical Center
Chicago, Illinois, 60612
University of Illinois at Chicago
Chicago, Illinois, 60612
Cook County Health System
Chicago, Illinois, 60615
University of Chicago
Chicago, Illinois, 60637
Urology Clinics of North Texas
Dallas, Texas, 75231
Los Angeles County
Los Angeles, California, 90033
University of Southern California
Los Angeles, California, 90033
Stanford University
Palo Alto, California, 94304
University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
Montefiore Medical Center
The Bronx, New York, 10467
Uropartners
Westchester, Illinois, 60154
About this study
Official title: SEPTA Trial: Stockholm3 Validation Study in a Multi-Ethnic Cohort for ProsTAte Cancer
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.
Read more
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.
Read the detailed description
Study Design and Procedures:
The research coordinator will explain the information contained within the consent. Additionally, patient's blood will be drawn prior to their biopsy.
Prior to the biopsy, blood will be collected in x2 ethylenediaminetetraacetic acid (EDTA) 4 ml tubes 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 1.5 ml of plasma). The decanted tube (with plasma) and the remaining EDTA tube (with whole blood) is then frozen and stored at the designated participating institutional site. It will be stored at -20 Celsius until being shipped. The SEPTA specific blood collection is followed by the following collaborators: Uropartners, University of Illinois at Chicago, University of Chicago, Rush Medical Center, Montefiore, University of Texas Health Science Center of San Antonio, Urology Clinics of North Texas, University of Southern California Keck School of Medicine, Los Angeles County Hospital, Stanford University.
Additional samples from University Health Network (Toronto), Northwestern Medicine, John H. Stroger, Jr. Hospital of Cook County, and Cook County Health System (Chicago) will be included from biobanked sources which were prospective collected meeting inclusion and exclusion criteria.
Patient data will be stored in a REDCap database, hosted on Sweden's secure server. Data will be stored for the duration of the study, and 5 years afterwards for data analysis purposes.
Consented patients will be tracked by patient logs by each participating institution. The medical record number will be collected to keep a consistent identifier for data collection by key site personnel. Once all the patient data is recorded the data will be exported from REDCap with the MRN removed. There will be no patient identifiers used at the Karolinska Institute or A3P lab. The following PHI and non-PHI information will be logged of the patient:
PHI:
Medical record number (MRN)
Non-PHI Demographic data
- Stockholm3 Identification number
- Race
- Zip code
Clinical data
- Total PSA
- Age on sampling date [years]
- Family history of prostate cancer
- Use of 5-alpha reductase inhibitors
- Earlier biopsy conducted
- Prostate volume [Prostate volume as measure with US]
- Digital rectal exam status [Benign/normal, Nodule/induration felt, Asymmetry, Not performed]
AND
Outcome data - Results from biopsy performed immediately after blood venipuncture, i.e.:
Results will be separated into targeted biopsy cores and systematic biopsy cores
- Gleason Score 1
- Gleason Score 2
- Gleason Sum
- Cancer length (mm) (total and highest grade)
- Number of cores
- Number of positive cores
- Time to perform biopsy after blood draw [days]
- Results from MRI, i.e. Prostate Imaging Reporting \& Data System (PIRADS) (0, 1, 2, 3, 4, 5)
Permitted use:
To run the Stockholm3 test defined by Gronberg et al AND Ancestry informative genetic markers
Samples will be shipped to the Uppsala based laboratory (A23 Laboratory) in Sweden for analysis. Each patient will have two blood samples (plasma and whole blood) and will be frozen at -20 Celsius. The blood samples will then be tested for quantitative levels of serum protein levels and DNA will be extracted from white blood cells and will be tested for gene and small nucleotide polymorphic (SNPs) germline mutations and variants .
Genotyping will be performed using custom genotyping assays. Plasma will be used for protein analysis. Plasma protein analysis will be performed using a custom protein assays including total and free PSA, human glandular kallikrein 2 (hK2), microseminoprotein-beta (MSMB), and Macrophage inhibitory cytokine 1 (MIC-1). PSA will be tested with a commercial assay.
Based on the results from the plasma protein analysis, the genetic analysis and clinical data, the Stockholm3 Risk Score will be calculated. The participants' samples will be treated in accordance with the regulations of Sweden at the laboratory based in Uppsala, Sweden.
Results of the tests will not be shared with the patient, nor will the results change or impact medical decisions.
Expected Risks/Benefits
Anticipated Risks:
As this is retrospective analysis of deidentified patient information as well as deidentified biospecimens, there are few anticipated risks. A confidentiality breach as well as loss of privacy are possible, however every effort will be made to minimize this risk.
Anticipated Benefits:
Participants will advance scientific and clinical knowledge. Participants will also receive a small payment for the time and involvement in the study.
Data Collection and Management Procedures
This study will utilize REDCap (Research Electronic Data Capture), a software toolset and workflow methodology for electronic collection and management of clinical and research data, to collect and store data. The Karolinska Institute Information Technology (KI-IT) Department will be used as a central location for data processing and management. REDCap is hosted by KI-IT in the Biomedicum (Solnavägen 9, Solna, Sweden 17165)
Data Analysis
Data analysis will be performed by the PI, co-investigators and/or key research personnel.
Quality Control and Quality Assurance
Key research personnel will be responsible for ensuring all data collected adheres to the protocol.
Data and Safety Monitoring
This study is minimal risk and all efforts will be made to ensure there are no confidentiality breaches as well as no loss of privacy.
Statistical Considerations
Power analysis This study is being conducted among several sites and thus pooled analysis will be performed. Based on the framework developed a two-sided alpha of 0.05, 250 men in each ethnicity gives 80% power to detect 10 percentage points differences in sensitivity and/or specificity of the Stockholm3 test across different ethnicities. Pooled data from several sites will allow for comparison between non-Hispanic White, Africa/Black, Asian, and Hispanic White men. Within each ethnicity group of 250 men, the same sample size gives a 90% power for detecting differences in area under curve (AUC) between Stockholm3 and PSA for detection of PC that are at least 10 percentage points (primary aim).
Goal accruement is 500 men within each race/ethnicity, interim analysis will be performed when 250 men in each race/ethnicity is enrolled.
Data Analysis Descriptive univariate statistics will be used to compare groups. Binary endpoints will be assessed with a logistic regression model. Statistical analysis will involve logistic regression modeling, AUC calculation, calibration analyses and calculation of basic performance characteristics (sensitivity, specificity and predictive values).
Regulatory Requirements
Informed Consent The participants indicate their consent to participate in the study by signing informed consents for accessing medical records, conducting genetic research and undergoing venipuncture for blood samples.
Subject Confidentiality Data used for this study will be stored in REDCaps and all data transferred between institutions will remain deidentified throughout the study.
Unanticipated Problems Any unanticipated problems will be immediately reported to the Site-specific ethical review board by designated research personnel.
- Conditions
- Prostate Cancer (Diagnosis)
- Being tested
- The Stockholm3 test
- Medical subject headings
- Prostatic Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Stockholm3 testDiagnostic test
Also called Diagnostic Test: Custom ancestry informative genetic markers
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Diagnostic Test: The Stockholm3 test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: On prostate biopsy immediately following PSA
Secondary outcomes (1)
National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk prostate cancer or higher risk
National Comprehensive Cancer Network Unfavorable intermediate risk prostate cancer or higher risk. National Comprehensive Cancer Network risk stratification scores range from very low risk, low risk, intermediate risk, high risk and very high risk. Intermediate risk is stratified into favorable intermediate risk and unfavorable intermediate risk. The higher the risk the worse the outcome
Measured: On prostate biopsy immediately following PSA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2020
- Study start15 Dec 2019
- Primary completion15 Jul 2023
- Study completion15 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Prostate Cancer (Diagnosis)Studies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois Chicago, UroPartners, University of Chicago, Rush University Medical Center, Montefiore Medical Center, The University of Texas Health Science Center at San Antonio, Cook County Health & Hospitals System, Cook County Health, Stanford University, Northwestern Medicine, University of Southern California, University Health Network, Toronto, Urology Clinics of North Texas, LAC+USC Medical Center
- Responsible party
- Principal investigator, Henrik Grönberg, Karolinska Institutet
- Investigators
- Henrik Grönberg, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04583072
- Sponsor's protocol ID
- KarolinskaI3
- Acronym
- SEPTA
- Status last verified
- Oct 2024
- First submitted
- 28 Sep 2020
- Last updated
- 21 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, Briganti A, Budaus L, Hellawell G, Hindley RG, Roobol MJ, Eggener S, Ghei M, Villers A, Bladou F, Villeirs GM, Virdi J, Boxler S, Robert G, Singh PB, Venderink W, Hadaschik BA, Ruffion A, Hu JC, Margolis D, Crouzet S, Klotz L, Taneja SS, Pinto P, Gill I, Allen C, Giganti F, Freeman A, Morris S, Punwani S, Williams NR, Brew-Graves C, Deeks J, Takwoingi Y, Emberton M, Moore CM; PRECISION Study Group Collaborators. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med. 2018 May 10;378(19):1767-1777. doi: 10.1056/NEJMoa1801993. Epub 2018 Mar 18.
PubMed 29552975Gronberg H, Adolfsson J, Aly M, Nordstrom T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M. Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study. Lancet Oncol. 2015 Dec;16(16):1667-76. doi: 10.1016/S1470-2045(15)00361-7. Epub 2015 Nov 10.
PubMed 26563502Strom P, Nordstrom T, Aly M, Egevad L, Gronberg H, Eklund M. The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex Test Potential. Eur Urol. 2018 Aug;74(2):204-210. doi: 10.1016/j.eururo.2017.12.028. Epub 2018 Jan 10.
PubMed 29331214Moller A, Olsson H, Gronberg H, Eklund M, Aly M, Nordstrom T. The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort. Prostate Cancer Prostatic Dis. 2019 Mar;22(1):137-142. doi: 10.1038/s41391-018-0082-5. Epub 2018 Aug 31.
PubMed 30171228Vigneswaran HT, Discacciati A, Gann PH, Gronberg H, Eklund M, Abern MR. Ethnic variation in prostate cancer detection: a feasibility study for use of the Stockholm3 test in a multiethnic U.S. cohort. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):120-127. doi: 10.1038/s41391-020-0250-2. Epub 2020 Jul 8.
PubMed 32641739Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
PubMed 29313949Potts JM, Lutz M, Walker E, Modlin C, Klein E. Trends in PSA, age and prostate cancer detection among black and white men from 1990-2006 at a tertiary care center. Cancer. 2010 Aug 15;116(16):3910-5. doi: 10.1002/cncr.25124.
PubMed 20564087Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jul 17;157(2):120-34. doi: 10.7326/0003-4819-157-2-201207170-00459.
PubMed 22801674Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS, Concepcion R, David RD, Deck KB, Dumbadze I, Gambla M, Grable MS, Henderson RJ, Karsh L, Krisch EB, Langford TD, Lin DW, McGee SM, Munoz JJ, Pieczonka CM, Rieger-Christ K, Saltzstein DR, Scott JW, Shore ND, Sieber PR, Waldmann TM, Wolk FN, Zappala SM. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015 Sep;68(3):464-70. doi: 10.1016/j.eururo.2014.10.021. Epub 2014 Oct 27.
PubMed 25454615de la Calle C, Patil D, Wei JT, Scherr DS, Sokoll L, Chan DW, Siddiqui J, Mosquera JM, Rubin MA, Sanda MG. Multicenter Evaluation of the Prostate Health Index to Detect Aggressive Prostate Cancer in Biopsy Naive Men. J Urol. 2015 Jul;194(1):65-72. doi: 10.1016/j.juro.2015.01.091. Epub 2015 Jan 28.
PubMed 25636659Roobol MJ, Verbeek JFM, van der Kwast T, Kummerlin IP, Kweldam CF, van Leenders GJLH. Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth. Eur Urol. 2017 Jul;72(1):45-51. doi: 10.1016/j.eururo.2017.01.033. Epub 2017 Feb 2.
PubMed 28162815Ankerst DP, Straubinger J, Selig K, Guerrios L, De Hoedt A, Hernandez J, Liss MA, Leach RJ, Freedland SJ, Kattan MW, Nam R, Haese A, Montorsi F, Boorjian SA, Cooperberg MR, Poyet C, Vertosick E, Vickers AJ. A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts. Eur Urol. 2018 Aug;74(2):197-203. doi: 10.1016/j.eururo.2018.05.003. Epub 2018 May 16.
PubMed 29778349Ankerst DP, Hoefler J, Bock S, Goodman PJ, Vickers A, Hernandez J, Sokoll LJ, Sanda MG, Wei JT, Leach RJ, Thompson IM. Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer. Urology. 2014 Jun;83(6):1362-7. doi: 10.1016/j.urology.2014.02.035.
PubMed 24862395Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000 Jul 13;343(2):78-85. doi: 10.1056/NEJM200007133430201.
PubMed 10891514Gronberg H, Eklund M, Picker W, Aly M, Jaderling F, Adolfsson J, Landquist M, Haug ES, Strom P, Carlsson S, Nordstrom T. Prostate Cancer Diagnostics Using a Combination of the Stockholm3 Blood Test and Multiparametric Magnetic Resonance Imaging. Eur Urol. 2018 Dec;74(6):722-728. doi: 10.1016/j.eururo.2018.06.022. Epub 2018 Jul 9.
PubMed 30001824
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SEPTA Trial: Stockholm3 Validation Study in a Multi-Ethnic Cohort for ProsTAte Cancer
- ClinicalTrials.gov ID
- NCT04583072
- Acronym / sponsor ID
- SEPTA / KarolinskaI3
- Conditions
- Prostate Cancer (Diagnosis)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,152 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- University of Illinois Chicago, UroPartners, University of Chicago, Rush University Medical Center, Montefiore Medical Center, The University of Texas Health Science Center at San Antonio, Cook County Health & Hospitals System, Cook County Health, Stanford University, Northwestern Medicine, University of Southern California, University Health Network, Toronto, Urology Clinics of North Texas, LAC+USC Medical Center
- Study start
- 15 Dec 2019 (actual)
- Primary completion
- 15 Jul 2023 (actual)
- Study completion
- 15 Jul 2023 (actual)
- First posted
- 12 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Design and Procedures:
The research coordinator will explain the information contained within the consent. Additionally, patient's blood will be drawn prior to their biopsy.
Prior to the biopsy, blood will be collected in x2 ethylenediaminetetraacetic acid (EDTA) 4 ml tubes 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 1.5 ml of plasma). The decanted tube (with plasma) and the remaining EDTA tube (with whole blood) is then frozen and stored at the designated participating institutional site. It will be stored at -20 Celsius until being shipped. The SEPTA specific blood collection is followed by the following collaborators: Uropartners, University of Illinois at Chicago, University of Chicago, Rush Medical Center, Montefiore, University of Texas Health Science Center of San Antonio, Urology Clinics of North Texas, University of Southern California Keck School of Medicine, Los Angeles County Hospital, Stanford University.
Additional samples from University Health Network (Toronto), Northwestern Medicine, John H. Stroger, Jr. Hospital of Cook County, and Cook County Health System (Chicago) will be included from biobanked sources which were prospective collected meeting inclusion and exclusion criteria.
Patient data will be stored in a REDCap database, hosted on Sweden's secure server. Data will be stored for the duration of the study, and 5 years afterwards for data analysis purposes.
Consented patients will be tracked by patient logs by each participating institution. The medical record number will be collected to keep a consistent identifier for data collection by key site personnel. Once all the patient data is recorded the data will be exported from REDCap with the MRN removed. There will be no patient identifiers used at the Karolinska Institute or A3P lab. The following PHI and non-PHI information will be logged of the patient:
PHI:
Medical record number (MRN)
Non-PHI Demographic data
- Stockholm3 Identification number
- Race
- Zip code
Clinical data
- Total PSA
- Age on sampling date [years]
- Family history of prostate cancer
- Use of 5-alpha reductase inhibitors
- Earlier biopsy conducted
- Prostate volume [Prostate volume as measure with US]
- Digital rectal exam status [Benign/normal, Nodule/induration felt, Asymmetry, Not performed]
AND
Outcome data - Results from biopsy performed immediately after blood venipuncture, i.e.:
Results will be separated into targeted biopsy cores and systematic biopsy cores
- Gleason Score 1
- Gleason Score 2
- Gleason Sum
- Cancer length (mm) (total and highest grade)
- Number of cores
- Number of positive cores
- Time to perform biopsy after blood draw [days]
- Results from MRI, i.e. Prostate Imaging Reporting \& Data System (PIRADS) (0, 1, 2, 3, 4, 5)
Permitted use:
To run the Stockholm3 test defined by Gronberg et al AND Ancestry informative genetic markers
Samples will be shipped to the Uppsala based laboratory (A23 Laboratory) in Sweden for analysis. Each patient will have two blood samples (plasma and whole blood) and will be frozen at -20 Celsius. The blood samples will then be tested for quantitative levels of serum protein levels and DNA will be extracted from white blood cells and will be tested for gene and small nucleotide polymorphic (SNPs) germline mutations and variants .
Genotyping will be performed using custom genotyping assays. Plasma will be used for protein analysis. Plasma protein analysis will be performed using a custom protein assays including total and free PSA, human glandular kallikrein 2 (hK2), microseminoprotein-beta (MSMB), and Macrophage inhibitory cytokine 1 (MIC-1). PSA will be tested with a commercial assay.
Based on the results from the plasma protein analysis, the genetic analysis and clinical data, the Stockholm3 Risk Score will be calculated. The participants' samples will be treated in accordance with the regulations of Sweden at the laboratory based in Uppsala, Sweden.
Results of the tests will not be shared with the patient, nor will the results change or impact medical decisions.
Expected Risks/Benefits
Anticipated Risks:
As this is retrospective analysis of deidentified patient information as well as deidentified biospecimens, there are few anticipated risks. A confidentiality breach as well as loss of privacy are possible, however every effort will be made to minimize this risk.
Anticipated Benefits:
Participants will advance scientific and clinical knowledge. Participants will also receive a small payment for the time and involvement in the study.
Data Collection and Management Procedures
This study will utilize REDCap (Research Electronic Data Capture), a software toolset and workflow methodology for electronic collection and management of clinical and research data, to collect and store data. The Karolinska Institute Information Technology (KI-IT) Department will be used as a central location for data processing and management. REDCap is hosted by KI-IT in the Biomedicum (Solnavägen 9, Solna, Sweden 17165)
Data Analysis
Data analysis will be performed by the PI, co-investigators and/or key research personnel.
Quality Control and Quality Assurance
Key research personnel will be responsible for ensuring all data collected adheres to the protocol.
Data and Safety Monitoring
This study is minimal risk and all efforts will be made to ensure there are no confidentiality breaches as well as no loss of privacy.
Statistical Considerations
Power analysis This study is being conducted among several sites and thus pooled analysis will be performed. Based on the framework developed a two-sided alpha of 0.05, 250 men in each ethnicity gives 80% power to detect 10 percentage points differences in sensitivity and/or specificity of the Stockholm3 test across different ethnicities. Pooled data from several sites will allow for comparison between non-Hispanic White, Africa/Black, Asian, and Hispanic White men. Within each ethnicity group of 250 men, the same sample size gives a 90% power for detecting differences in area under curve (AUC) between Stockholm3 and PSA for detection of PC that are at least 10 percentage points (primary aim).
Goal accruement is 500 men within each race/ethnicity, interim analysis will be performed when 250 men in each race/ethnicity is enrolled.
Data Analysis Descriptive univariate statistics will be used to compare groups. Binary endpoints will be assessed with a logistic regression model. Statistical analysis will involve logistic regression modeling, AUC calculation, calibration analyses and calculation of basic performance characteristics (sensitivity, specificity and predictive values).
Regulatory Requirements
Informed Consent The participants indicate their consent to participate in the study by signing informed consents for accessing medical records, conducting genetic research and undergoing venipuncture for blood samples.
Subject Confidentiality Data used for this study will be stored in REDCaps and all data transferred between institutions will remain deidentified throughout the study.
Unanticipated Problems Any unanticipated problems will be immediately reported to the Site-specific ethical review board by designated research personnel.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Non-Hispanic/Latino White/Caucasian men | – | Diagnostic Test: The Stockholm3 testSelf-identified as White Non-Hispanic men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer |
| African/Black men | – | Diagnostic Test: The Stockholm3 testSelf-identified as African or Black men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer |
| Hispanic/Latino White/Caucasian men | – | Diagnostic Test: The Stockholm3 testSelf-identified as White Hispanic men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer |
| Asian men | – | Diagnostic Test: The Stockholm3 testSelf-identified as Asian men, with age range (45.0 - 75.0 years), without prior evidence of prostate cancer |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- Male only
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The Stockholm3 testAlso: Diagnostic Test: Custom ancestry informative genetic markersVenipuncture: 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. | Diagnostic test | African/Black men, Asian men, Hispanic/Latino White/Caucasian men, Non-Hispanic/Latino White/Caucasian men |
Primary outcome
Gleason Grade Group 2 Prostate Cancer
Time frame: On prostate biopsy immediately following PSA
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.
1 secondary outcome
National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk prostate cancer or higher risk
Time frame: On prostate biopsy immediately following PSA
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Background: PubMed 29552975Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, Briganti A, Budaus L, Hellawell G, Hindley RG, Roobol MJ, Eggener S, Ghei M, Villers A, Bladou F, Villeirs GM, Virdi J, Boxler S, Robert G, Singh PB, Venderink W, Hadaschik BA, Ruffion A, Hu JC, Margolis D, Crouzet S, Klotz L, Taneja SS, Pinto P, Gill I, Allen C, Giganti F, Freeman A, Morris S, Punwani S, Williams NR, Brew-Graves C, Deeks J, Takwoingi Y, Emberton M, Moore CM; PRECISION Study Group Collaborators. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med. 2018 May 10;378(19):1767-1777. doi: 10.1056/NEJMoa1801993. Epub 2018 Mar 18.
- Background: PubMed 26563502Gronberg H, Adolfsson J, Aly M, Nordstrom T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M. Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study. Lancet Oncol. 2015 Dec;16(16):1667-76. doi: 10.1016/S1470-2045(15)00361-7. Epub 2015 Nov 10.
- Background: PubMed 29331214Strom P, Nordstrom T, Aly M, Egevad L, Gronberg H, Eklund M. The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex Test Potential. Eur Urol. 2018 Aug;74(2):204-210. doi: 10.1016/j.eururo.2017.12.028. Epub 2018 Jan 10.
- Background: PubMed 30171228Moller A, Olsson H, Gronberg H, Eklund M, Aly M, Nordstrom T. The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort. Prostate Cancer Prostatic Dis. 2019 Mar;22(1):137-142. doi: 10.1038/s41391-018-0082-5. Epub 2018 Aug 31.
- Background: PubMed 32641739Vigneswaran HT, Discacciati A, Gann PH, Gronberg H, Eklund M, Abern MR. Ethnic variation in prostate cancer detection: a feasibility study for use of the Stockholm3 test in a multiethnic U.S. cohort. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):120-127. doi: 10.1038/s41391-020-0250-2. Epub 2020 Jul 8.
- Background: PubMed 29313949Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
- Background: PubMed 20564087Potts JM, Lutz M, Walker E, Modlin C, Klein E. Trends in PSA, age and prostate cancer detection among black and white men from 1990-2006 at a tertiary care center. Cancer. 2010 Aug 15;116(16):3910-5. doi: 10.1002/cncr.25124.
- Background: PubMed 22801674Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jul 17;157(2):120-34. doi: 10.7326/0003-4819-157-2-201207170-00459.
- Background: PubMed 25454615Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS, Concepcion R, David RD, Deck KB, Dumbadze I, Gambla M, Grable MS, Henderson RJ, Karsh L, Krisch EB, Langford TD, Lin DW, McGee SM, Munoz JJ, Pieczonka CM, Rieger-Christ K, Saltzstein DR, Scott JW, Shore ND, Sieber PR, Waldmann TM, Wolk FN, Zappala SM. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015 Sep;68(3):464-70. doi: 10.1016/j.eururo.2014.10.021. Epub 2014 Oct 27.
- Background: PubMed 25636659de la Calle C, Patil D, Wei JT, Scherr DS, Sokoll L, Chan DW, Siddiqui J, Mosquera JM, Rubin MA, Sanda MG. Multicenter Evaluation of the Prostate Health Index to Detect Aggressive Prostate Cancer in Biopsy Naive Men. J Urol. 2015 Jul;194(1):65-72. doi: 10.1016/j.juro.2015.01.091. Epub 2015 Jan 28.
- Background: PubMed 28162815Roobol MJ, Verbeek JFM, van der Kwast T, Kummerlin IP, Kweldam CF, van Leenders GJLH. Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth. Eur Urol. 2017 Jul;72(1):45-51. doi: 10.1016/j.eururo.2017.01.033. Epub 2017 Feb 2.
- Background: PubMed 29778349Ankerst DP, Straubinger J, Selig K, Guerrios L, De Hoedt A, Hernandez J, Liss MA, Leach RJ, Freedland SJ, Kattan MW, Nam R, Haese A, Montorsi F, Boorjian SA, Cooperberg MR, Poyet C, Vertosick E, Vickers AJ. A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts. Eur Urol. 2018 Aug;74(2):197-203. doi: 10.1016/j.eururo.2018.05.003. Epub 2018 May 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik Grönberg, MD, PhD principal investigator
Karolinska Institutet
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer (Diagnosis), run by Karolinska Institutet at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gleason Grade Group 2 Prostate Cancer (time frame: On prostate biopsy immediately following PSA). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04583072, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024.