Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis
(2018) In Journal of Urology 199(6). p.1470-1474- Abstract
Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional markers add discrimination to the clinical predictors of patient age, digital rectal examination and prior biopsy, and the established molecular markers total and free prostate specific antigen. Materials and Methods: We performed an individual patient data meta-analysis of published studies in which the 4 kallikrein panel was measured in men... (More)
Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional markers add discrimination to the clinical predictors of patient age, digital rectal examination and prior biopsy, and the established molecular markers total and free prostate specific antigen. Materials and Methods: We performed an individual patient data meta-analysis of published studies in which the 4 kallikrein panel was measured in men undergoing prostate biopsy. We assess the improvement in discrimination associated with including intact prostate specific antigen and hK2 along with total and free prostate specific antigen in the statistical model. Results: Included in analysis were 14,510 men from a total of 10 studies. The fixed effects meta-analytical estimate of the discrimination of the model without intact prostate specific antigen and hK2 was 0.742 (95% CI 0.727–0.756) compared to 0.813 (95% CI 0.801–0.825) for the full kallikrein model. The 95% CIs did not overlap and the difference in discrimination was highly statistically significant (0.069, 95% CI 0.057–0.080, p <0.0001). Intact prostate specific antigen (increase in discrimination 0.059, 95% CI 0.050–0.069) and hK2 (increase in discrimination 0.024, 95% CI 0.020–0.029, each p <0.0001) added independently to the model. Conclusions: The clinical value of the panel could not be replicated using data readily available to urologists without measuring intact prostate specific antigen and hK2.
(Less)
- author
- Vickers, Andrew
; Vertosick, Emily A.
; Sjoberg, Daniel D.
; Hamdy, Freddie
; Neal, David
; Bjartell, Anders
LU
; Hugosson, Jonas
; Donovan, Jenny L.
; Villers, Arnauld
; Zappala, Stephen
and Lilja, Hans
LU
(Less) - organization
- publishing date
- 2018-01-31
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- digital rectal examination, early detection of cancer, kallikreins, prostate-specific antigen, prostatic neoplasms
- in
- Journal of Urology
- volume
- 199
- issue
- 6
- pages
- 1470 - 1474
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85045877819
- pmid:29366640
- ISSN
- 0022-5347
- DOI
- 10.1016/j.juro.2018.01.070
- language
- English
- LU publication?
- yes
- id
- 7ddd135a-a5c5-4567-b928-0f893035e0ae
- date added to LUP
- 2018-05-07 07:51:25
- date last changed
- 2024-06-24 14:06:36
@article{7ddd135a-a5c5-4567-b928-0f893035e0ae,
abstract = {{<p>Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional markers add discrimination to the clinical predictors of patient age, digital rectal examination and prior biopsy, and the established molecular markers total and free prostate specific antigen. Materials and Methods: We performed an individual patient data meta-analysis of published studies in which the 4 kallikrein panel was measured in men undergoing prostate biopsy. We assess the improvement in discrimination associated with including intact prostate specific antigen and hK2 along with total and free prostate specific antigen in the statistical model. Results: Included in analysis were 14,510 men from a total of 10 studies. The fixed effects meta-analytical estimate of the discrimination of the model without intact prostate specific antigen and hK2 was 0.742 (95% CI 0.727–0.756) compared to 0.813 (95% CI 0.801–0.825) for the full kallikrein model. The 95% CIs did not overlap and the difference in discrimination was highly statistically significant (0.069, 95% CI 0.057–0.080, p <0.0001). Intact prostate specific antigen (increase in discrimination 0.059, 95% CI 0.050–0.069) and hK2 (increase in discrimination 0.024, 95% CI 0.020–0.029, each p <0.0001) added independently to the model. Conclusions: The clinical value of the panel could not be replicated using data readily available to urologists without measuring intact prostate specific antigen and hK2.</p>}},
author = {{Vickers, Andrew and Vertosick, Emily A. and Sjoberg, Daniel D. and Hamdy, Freddie and Neal, David and Bjartell, Anders and Hugosson, Jonas and Donovan, Jenny L. and Villers, Arnauld and Zappala, Stephen and Lilja, Hans}},
issn = {{0022-5347}},
keywords = {{digital rectal examination; early detection of cancer; kallikreins; prostate-specific antigen; prostatic neoplasms}},
language = {{eng}},
month = {{01}},
number = {{6}},
pages = {{1470--1474}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Journal of Urology}},
title = {{Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis}},
url = {{http://dx.doi.org/10.1016/j.juro.2018.01.070}},
doi = {{10.1016/j.juro.2018.01.070}},
volume = {{199}},
year = {{2018}},
}