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.
(Less)
- author
- Kim, Eric H.
; Andriole, Gerald L.
; Crawford, E. David
; Sjoberg, Daniel
; Assel, Melissa
; Vickers, Andrew J
and Lilja, Hans
LU
- organization
- publishing date
- 2016-11-01
- 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
- pmid:27810449
- 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
- 2024-06-10 16:12:39
@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 <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}},
keywords = {{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}},
doi = {{10.1016/j.juro.2016.10.089}},
year = {{2016}},
}