We will determine whether kallikrein forms (prostate-specific antigen [PSA] and kallikrein 2 [hK2]) measured in men aged 44 - 50 predict subsequent metastases or death from prostate cancer. No previous study have evaluated whether a biomarker analyzed in a healthy volunteer population predicts metastases or cancer-specific death many years (typically 15-35 years) later. Low incidence of PSA testing in Sweden during enrollment (1974-1986) and long-term follow-up are prerequisites for our unique """"""""natural experiment"""""""". We do not ask """"""""can we detect prostate cancer?"""""""" but """"""""can we predict prostate cancers with important impact on quality of life or reduced life expectancy?"""""""" We wish to predict risk of metastases or death from prostate cancer to risk-stratify screening and chemoprevention strategies, which must be made before these efforts start;i.e. in age 44- 50. We will first determine whether highly optimized measures of PSA and hK2 in blood collected at age =50 predict later development of metastases or death from prostate cancer;go on to determine whether measures in a 2nd sample (collected 6 years later) enhances these predictions. We will build statistical models to predict an individual man's probability of metastases or death from prostate cancer using single, or repeated measures at ages 44 - 55. If these models have sufficient accuracy in the R21 phase, we will go on in the R33 phase to determine their accuracy on an independent cohort of 40,000 men. Many common problems are avoided. These include over-diagnosis: we know that PSA detects prostate cancer at early, curable stages with high sensitivity (but poor specificity), however, many PSA-detected cancers would never cause morbidity or mortality to the patient before he dies of other causes. Studies are also affected by selection bias: men with family history or other risk factors are more likely to attend screening;and lead-time bias, where apparent survival advantage only relates to early time of diagnosis. Regarding the key issue of over-diagnosis, our study endpoint is death, or metastatic disease. There will be little if any selection bias due to low incidence of PSA screening in our study cohorts. Due to the retrospective nature of the study, the participants are never influenced by any PSA-data, and we will not be subject to lead- time bias as we will not compare survival between screened vs. unscreened cohorts. Using blood samples taken in Sweden in the mid-1970s - 1980s, we were able to show that a single blood test at age 44 - 50 can predict prostate cancer up to 25 years later. As many more men are diagnosed with prostate cancer than who die from the disease, the current proposal is to extend our work to determine if we can predict prostate cancer death. If so, a single blood test could be used to identify men at highest risk from prostate cancer and particular efforts could then be made for intensive screening and chemoprevention for these individuals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA127768-03
Application #
8118945
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Divi, Rao L
Project Start
2008-03-14
Project End
2013-07-31
Budget Start
2011-08-18
Budget End
2013-07-31
Support Year
3
Fiscal Year
2011
Total Cost
$340,099
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Carlsson, Sigrid; Assel, Melissa; Ulmert, David et al. (2017) Screening for Prostate Cancer Starting at Age 50-54 Years. A Population-based Cohort Study. Eur Urol 71:46-52
Preston, Mark A; Batista, Julie L; Wilson, Kathryn M et al. (2016) Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer. J Clin Oncol 34:2705-11
Thorek, Daniel L J; Watson, Philip A; Lee, Sang-Gyu et al. (2016) Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis. Sci Transl Med 8:367ra167
Vickers, Andrew J; Eastham, James A; Scardino, Peter T et al. (2016) The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening. Urology 91:12-8
Bratt, Ola; Lilja, Hans (2015) Serum markers in prostate cancer detection. Curr Opin Urol 25:59-64
Grenvall, Carl; Magnusson, Cecilia; Lilja, Hans et al. (2015) Concurrent isolation of lymphocytes and granulocytes using prefocused free flow acoustophoresis. Anal Chem 87:5596-604
Nordström, Tobias; Vickers, Andrew; Assel, Melissa et al. (2015) Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer. Eur Urol 68:139-46
Stattin, Pär; Vickers, Andrew J; Sjoberg, Daniel D et al. (2015) Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study. Eur Urol 68:207-13
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
Ankerst, Donna P; Boeck, Andreas; Freedland, Stephen J et al. (2014) Evaluating the Prostate Cancer Prevention Trial High Grade Prostate Cancer Risk Calculator in 10 international biopsy cohorts: results from the Prostate Biopsy Collaborative Group. World J Urol 32:185-91

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