Skip to main content
Grant Details

Grant Number: 1R01CA179115-01A1 Interpret this number
Primary Investigator: Vickers, Andrew
Organization: Sloan-Kettering Inst Can Research
Project Title: Dynamic, Multi-Cohort Prediction Modeling of Prostate Biopsy Outcome
Fiscal Year: 2014


DESCRIPTION (provided by applicant): Prostate specific antigen (PSA) is the only molecular marker routinely used for the early detection of a common cancer, with approximately 75% of men aged 50 years or older having had at least one PSA test. The results of the European Randomized Study of Prostate Cancer, which assessed the value of PSA testing in men who would otherwise not be screened, offered qualified support for PSA testing, showing a modest reduction in prostate cancer mortality. Yet PSA remains an imperfect test. Although PSA is highly specific to the prostate gland, a modestly elevated PSA in blood is not specific to cancer as common benign conditions such as benign prostatic hyperplasia and prostatitis also lead to modest PSA elevations. Accordingly, most men with modestly elevated PSA do not have prostate cancer and it has been estimated that at least 750,000 American men are needlessly subjected to prostate biopsy. Prostate biopsy is not only inconvenient, with 1 in 3 men having to take two or more days from work, but can cause infection, urinary retention or other major complications. To aid the clinical decision as to whether biopsy an individual patient, several investigators have proposed risk prediction models that include information such as PSA level, age, family history and the results of the digital rectal exam (DRE). These models provide a predicted probability of a positive biopsy that can be used to aid patient counseling. However, current prediction models have often been shown to be inaccurate on external validation. One possible reason is that all of the numerous models currently available were developed using a single cohort, a highly problematic approach given important differences between cohorts. In this proposal, we will establish a large, international, multicenter collaboration that will share data on biopsy outcome to allow statistical prediction modeling that incorporates cohort characteristics. The collaboration includes centers in the US, Canada, the Caribbean, Germany and Italy; major academic centers as well as more community-based practices; those seeing predominately Caucasians and those with a racially-diverse group of patients. In total, we will have data on approximately 7000 biopsies per year, over 1000 of which will be in African-Americans or Hispanics. We will establish an informatics infrastructure to allow these centers to send harmonized data on biopsy outcomes to the statistical center. We will then create a prediction model that incorporates both patient-level factors (such as age and PSA) and those at the cohort-level (such as biopsy scheme). The model will be evaluated on an independent validation sample. We will formally test the hypothesis that including multiple cohorts in prediction modeling leads to more accurate models than those generated on single cohorts. As an additional aim, we will update the model as new data become available to evaluate "dynamic" modeling in contrast to traditional static models. We will also evaluate statistical methods for incorporating data on novel markers into existing prediction models.


Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort.
Authors: Clements M.B. , Vertosick E.A. , Guerrios-Rivera L. , De Hoedt A.M. , Hernandez J. , Liss M.A. , Leach R.J. , Freedland S.J. , Haese A. , Montorsi F. , et al. .
Source: European urology, 2022 Aug; 82(2), p. 163-169.
EPub date: 2021-12-31.
PMID: 34980493
Related Citations

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction.
Authors: Neumair M. , Kattan M.W. , Freedland S.J. , Haese A. , Guerrios-Rivera L. , De Hoedt A.M. , Liss M.A. , Leach R.J. , Boorjian S.A. , Cooperberg M.R. , et al. .
Source: BMC medical research methodology, 2022-07-21; 22(1), p. 200.
EPub date: 2022-07-21.
PMID: 35864460
Related Citations

Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials.
Authors: Gelfond J.A. , Hernandez B. , Goros M. , Ibrahim J.G. , Chen M.H. , Sun W. , Leach R.J. , Kattan M.W. , Thompson I.M. , Ankerst D.P. , et al. .
Source: BMC urology, 2022-03-26; 22(1), p. 45.
EPub date: 2022-03-26.
PMID: 35351104
Related Citations

Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools.
Authors: Tolksdorf J. , Kattan M.W. , Boorjian S.A. , Freedland S.J. , Saba K. , Poyet C. , Guerrios L. , De Hoedt A. , Liss M.A. , Leach R.J. , et al. .
Source: BMC medical research methodology, 2019-10-15; 19(1), p. 191.
EPub date: 2019-10-15.
PMID: 31615451
Related Citations

Redesigning Prostate Cancer Screening Strategies to Reduce Overdiagnosis.
Authors: Vickers A.J. .
Source: Clinical chemistry, 2019 Jan; 65(1), p. 39-41.
EPub date: 2018-10-01.
PMID: 30274977
Related Citations

Incorporation of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG into Prostate Cancer Prevention Trial Risk Calculator.
Authors: Ankerst D.P. , Goros M. , Tomlins S.A. , Patil D. , Feng Z. , Wei J.T. , Sanda M.G. , Gelfond J. , Thompson I.M. , Leach R.J. , et al. .
Source: European urology focus, 2019 Jan; 5(1), p. 54-61.
EPub date: 2018-02-13.
PMID: 29422418
Related Citations

Reporting and Interpreting Decision Curve Analysis: A Guide for Investigators.
Authors: Van Calster B. , Wynants L. , Verbeek J.F.M. , Verbakel J.Y. , Christodoulou E. , Vickers A.J. , Roobol M.J. , Steyerberg E.W. .
Source: European urology, 2018 Dec; 74(6), p. 796-804.
EPub date: 2018-09-19.
PMID: 30241973
Related Citations

Value of a Statistical Model Based on Four Kallikrein Markers in Blood, Commercially Available as 4Kscore, in All Reasonable Prostate Biopsy Subgroups.
Authors: Vickers A.J. , Vertosick E.A. , Sjoberg D.D. .
Source: European urology, 2018 Oct; 74(4), p. 535-536.
EPub date: 2018-06-11.
PMID: 29903434
Related Citations

A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts.
Authors: Ankerst D.P. , Straubinger J. , Selig K. , Guerrios L. , De Hoedt A. , Hernandez J. , Liss M.A. , Leach R.J. , Freedland S.J. , Kattan M.W. , et al. .
Source: European urology, 2018 Aug; 74(2), p. 197-203.
EPub date: 2018-05-16.
PMID: 29778349
Related Citations

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model: An Individual Patient Data Meta-Analysis.
Authors: Vickers A. , Vertosick E.A. , Sjoberg D.D. , Hamdy F. , Neal D. , Bjartell A. , Hugosson J. , Donovan J.L. , Villers A. , Zappala S. , et al. .
Source: The Journal of urology, 2018 Jun; 199(6), p. 1470-1474.
EPub date: 2018-01-31.
PMID: 29366640
Related Citations

The effect of 3-month finasteride challenge on biomarkers for predicting cancer outcome on biopsy: Results of a randomized trial.
Authors: Hernandez J. , Gelfond J. , Goros M. , Liss M.A. , Liang Y. , Ankerst D. , Thompson I.M. , Leach R.J. .
Source: PloS one, 2018; 13(10), p. e0204823.
EPub date: 2018-10-09.
PMID: 30300367
Related Citations

Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone: Meta-Analysis of Patients with Positive Digital Rectal Examination or Prostate Specific Antigen 10 ng/ml and Above.
Authors: Vickers A. , Vertosick E.A. , Sjoberg D.D. , Roobol M.J. , Hamdy F. , Neal D. , Bjartell A. , Hugosson J. , Donovan J.L. , Villers A. , et al. .
Source: The Journal of urology, 2017 Mar; 197(3 Pt 1), p. 607-613.
EPub date: 2016-09-28.
PMID: 27693450
Related Citations

Prostate Specific Antigen and Prostate Cancer in Chinese Men Undergoing Initial Prostate Biopsies Compared with Western Cohorts.
Authors: Chen R. , Sjoberg D.D. , Huang Y. , Xie L. , Zhou L. , He D. , Vickers A.J. , Sun Y. , Chinese Prostate Cancer Consortium , Prostate Biopsy Collaborative Group .
Source: The Journal of urology, 2017 Jan; 197(1), p. 90-96.
EPub date: 2016-09-02.
PMID: 27593477
Related Citations

Beyond prostate-specific antigen: utilizing novel strategies to screen men for prostate cancer.
Authors: Loeb S. , Lilja H. , Vickers A. .
Source: Current opinion in urology, 2016 Sep; 26(5), p. 459-65.
PMID: 27262138
Related Citations

Serial Percent Free Prostate Specific Antigen in Combination with Prostate Specific Antigen for Population Based Early Detection of Prostate Cancer.
Authors: Ankerst D.P. , Gelfond J. , Goros M. , Herrera J. , Strobl A. , Thompson I.M. , Hernandez J. , Leach R.J. .
Source: The Journal of urology, 2016 Aug; 196(2), p. 355-60.
EPub date: 2016-03-12.
PMID: 26979652
Related Citations

Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests.
Authors: Vickers A.J. , Van Calster B. , Steyerberg E.W. .
Source: BMJ (Clinical research ed.), 2016-01-25; 352, p. i6.
EPub date: 2016-01-25.
PMID: 26810254
Related Citations

Improving patient prostate cancer risk assessment: Moving from static, globally-applied to dynamic, practice-specific risk calculators.
Authors: Strobl A.N. , Vickers A.J. , Van Calster B. , Steyerberg E. , Leach R.J. , Thompson I.M. , Ankerst D.P. .
Source: Journal of biomedical informatics, 2015 Aug; 56, p. 87-93.
EPub date: 2015-05-16.
PMID: 25989018
Related Citations

The Next Generation of Clinical Decision Making Tools: Development of a Real-Time Prediction Tool for Outcome of Prostate Biopsy in Response to a Continuously Evolving Prostate Cancer Landscape.
Authors: Strobl A.N. , Thompson I.M. , Vickers A.J. , Ankerst D.P. .
Source: The Journal of urology, 2015 Jul; 194(1), p. 58-64.
EPub date: 2015-01-28.
PMID: 25636656
Related Citations

A simple-to-use method incorporating genomic markers into prostate cancer risk prediction tools facilitated future validation.
Authors: Grill S. , Fallah M. , Leach R.J. , Thompson I.M. , Hemminki K. , Ankerst D.P. .
Source: Journal of clinical epidemiology, 2015 May; 68(5), p. 563-73.
EPub date: 2015-01-14.
PMID: 25684153
Related Citations

Nonlinear modeling was applied thoughtfully for risk prediction: the Prostate Biopsy Collaborative Group.
Authors: Nieboer D. , Vergouwe Y. , Roobol M.J. , Ankerst D.P. , Kattan M.W. , Vickers A.J. , Steyerberg E.W. , Prostate Biopsy Collaborative Group .
Source: Journal of clinical epidemiology, 2015 Apr; 68(4), p. 426-34.
EPub date: 2014-11-29.
PMID: 25777297
Related Citations

Back to Top