Approximately one million biopsies for prostate cancer are conducted each year in the US. The majority are unnecessary: the most common reason for a prostate biopsy is an elevated level of prostate-specific antigen (PSA) in the blood, but most men with elevated PSA do not have prostate cancer. In seven separate studies, involving over 7500 men and 2250 cancers, we have shown that a statistical model based on measuring isoforms of PSA, and kallikrein-related peptidase 2 (hK2), is a highly accurate predictor of prostate biopsy outcome in men with elevated PSA. In our primary study, the area-under-the-curve of the model was applied to an independent validation set was 0.76, far higher than PSA alone (0.64). We have also conducted decision analyses demonstrating that use of the statistical model to determine referral for prostate biopsy would reduce the number of unnecessary biopsies by about half, but miss only a small number of cancers, almost all of which would be the sort of low grade and stage cancers typically thought to constitute overdiagnosis. All of our prior studies were retrospectively conducted on European populations using frozen archived samples analyzed in a single research laboratory. In this proposal, we will first seek to evaluate the statistical model when applied retrospectively to a US cohort. We will then test whether independent clinical laboratories can measure the panel of four kallikreins accurately using control samples. We will then go on to prospectively collect research blood from patients before a scheduled biopsy. This sample will be analyzed locally, in real time, although the scheduled biopsy will continue irrespective of marker results, with biopsy outcome compared with the prediction from the statistical model. Finally, we will explore how implementation of the model would affect clinical practice using decision-analytic simulation and a vignette study.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA160816-03
Application #
8676733
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Kagan, Jacob
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
City
New York
State
NY
Country
United States
Zip Code
10065
Vickers, Andrew J; Edwards, Kelly; Cooperberg, Matthew R et al. (2014) A simple schema for informed decision making about prostate cancer screening. Ann Intern Med 161:441-2
Cuzick, Jack; Thorat, Mangesh A; Andriole, Gerald et al. (2014) Prevention and early detection of prostate cancer. Lancet Oncol 15:e484-92
Carlsson, Sigrid; Assel, Melissa; Sjoberg, Daniel et al. (2014) Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study. BMJ 348:g2296
Vickers, Andrew J; Sjoberg, Daniel D; Ulmert, David et al. (2014) Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen. BMC Med 12:26
Nazarian, Arpi; Lawlor, Kevin; Yi, San San et al. (2014) Inhibition of circulating dipeptidyl peptidase 4 activity in patients with metastatic prostate cancer. Mol Cell Proteomics 13:3082-96
Schröder, Fritz H; Hugosson, Jonas; Roobol, Monique J et al. (2014) Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 384:2027-35
Väänänen, Riina-Minna; Lilja, Hans; Kauko, Leni et al. (2014) Cancer-associated changes in the expression of TMPRSS2-ERG, PCA3, and SPINK1 in histologically benign tissue from cancerous vs noncancerous prostatectomy specimens. Urology 83:511.e1-7
Bancroft, Elizabeth K; Page, Elizabeth C; Castro, Elena et al. (2014) Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol 66:489-99
Ahmad-Tajudin, Asilah; Adler, Belinda; Ekstrom, Simon et al. (2014) MALDI-target integrated platform for affinity-captured protein digestion. Anal Chim Acta 807:1-8
Bryant, Richard J; Lilja, Hans (2014) Emerging PSA-based tests to improve screening. Urol Clin North Am 41:267-76

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