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2014 ASCO Annual Meeting, 4KSCORE, Four Kallikrein Markers, opko Health

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Improving the specificity of prostate cancer screening for early detection of lethal disease. ( http://meetinglibrary.asco.org/content/133629-144?utm_content=8913138&utm_medium=social&utm_source=twitter )

Meeting:
2014 ASCO Annual Meeting

Category:
Genitourinary (Prostate) Cancer

Subcategory:
Prostate Cancer

Session Type and Session Title:
General Poster Session, Genitourinary (Prostate) Cancer

Abstract Number:
5081

Citation:
J Clin Oncol 32:5s, 2014 (suppl; abstr 5081)

Author(s):
Hans Lilja, Andrew J. Vickers, Daniel Sjoberg, Robert Johansson, Torvald Granfors, Mattias Johansson, Kim Pettersson, Peter T. Scardino, Göran Hallmans, Pär Stattin; Memorial Sloan-Kettering Cancer Center, New York, NY; Umeå University, Umeå, Sweden; Central Hospital, Västerås, Sweden; The International Agency for Research, Lyon, France; University of Turku, Turku, Finland

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures ( http://apps.asco.org/coidisplay/generateAbstractCOI.aspx?abstractId=133629 )

Abstract:

Background: PSA is used to detect prostate cancer, but many men need to be screened, biopsied, and diagnosed to prevent one cancer death. We sought to increase the specificity of screening for lethal prostate cancer. Methods: We conducted a nested case-control study to determine the relationship between four kallikrein markers (kallikrein related peptidase 2, total, free, and intact PSA) and long-term risk of metastasis. Of the 40,379 men providing blood at age 40, 50, and 60 during 1986-2009 for the Västerbotten Intervention Project, 12,561 were followed for over 15 years. Using the Swedish Cancer Registry, 1,423 incident prostate cancer cases and 235 men with evidence of distant metastases were identified. Kallikrein markers were measured in cryopreserved blood from cases and controls. Results: Risk of prostate cancer metastasis at 20 years was higher (16-fold at age 60, 7-fold at age 50, 3-fold at age 40) among men with PSA in top quartile than men with PSA below median. Most metastatic cases occurred in men with PSA in top quartile at age 50 (69%) or 60 (73%). Among men with PSA levels above median, a pre-specified model based on four kallikrein markers improved prediction of distant metastasis documented 10-20 years later compared to PSA alone. Among men with PSA =2 ng/ml at age 50, discrimination increased from 0.77 (PSA alone) to 0.88 (kallikrein panel); for men with PSA =2 ng/ml at age 60, discrimination increased from 0.81 to 0.87. We also conducted a decision analysis evaluating hypothetical outcomes had the panel been used to aid decisions about biopsy in this cohort. Using the biopsy cutoff used in the European randomized prostate cancer screening trial (PSA =3 ng/ml) would have resulted in biopsies performed on 15.5% of men with blood drawn at age 60. This rate would have been reduced by 38% if biopsy were restricted to those with =7.5% risk of high-grade cancer according to the panel. However, 10 to 15-year risk of distant metastases was only 0.18% to 1.16% in this group; a 15-year risk of metastases less than an eighth of that for those with PSA =3 ng/ml and =7.5% risk score. Conclusions: The specificity of PSA screening can be improved by focusing on men with modestly elevated PSA at age 50-60 and by reflex testing of four kallikrein markers.