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Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel

Kim, Eric H.; Andriole, Gerald L.; Crawford, E. David; Sjoberg, Daniel; Assel, Melissa; Vickers, Andrew J and Lilja, Hans LU (2016) In Journal of Urology
Abstract

Purpose: We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Materials and Methods: Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. Results: The detection of high grade prostate cancer in 94 men (10%)... (More)

Purpose: We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Materials and Methods: Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. Results: The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p <0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). Conclusions: In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Biopsy, Kallikreins, Mass screening, Prostate-specific antigen, Prostatic neoplasms
in
Journal of Urology
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85014091135
  • wos:000398050600028
ISSN
0022-5347
DOI
10.1016/j.juro.2016.10.089
language
English
LU publication?
yes
id
5fcf39fb-7046-44a8-aaf8-0677984ff42e
date added to LUP
2017-03-24 15:47:17
date last changed
2017-10-22 05:28:40
@article{5fcf39fb-7046-44a8-aaf8-0677984ff42e,
  abstract     = {<p>Purpose: We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Materials and Methods: Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. Results: The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p &lt;0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). Conclusions: In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC.</p>},
  author       = {Kim, Eric H. and Andriole, Gerald L. and Crawford, E. David and Sjoberg, Daniel and Assel, Melissa and Vickers, Andrew J and Lilja, Hans},
  issn         = {0022-5347},
  keyword      = {Biopsy,Kallikreins,Mass screening,Prostate-specific antigen,Prostatic neoplasms},
  language     = {eng},
  month        = {11},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel},
  url          = {http://dx.doi.org/10.1016/j.juro.2016.10.089},
  year         = {2016},
}