Predictive value of AZGP1 following radical prostatectomy for prostate cancer: A cohort study and meta-analysis

Gitte Kristensen; Kasper Drimer Berg; Birgitte Grønkær Toft; Hein Vincent Stroomberg; Rosalie Nolley; James D. Brooks; Klaus Brasso; Martin Andreas Roder

doi:10.1136/jclinpath-2019-205940

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: A cohort study and meta-analysis

Gitte Kristensen^*, Kasper Drimer Berg, Birgitte Grønkær Toft, Hein Vincent Stroomberg, Rosalie Nolley, James D. Brooks, Klaus Brasso, Martin Andreas Roder

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

1 Citationer (Scopus)

Abstract

Aims Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). Methods The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. Results Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). Conclusions Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Pathology
Vol/bind	72
Udgave nummer	10
Sider (fra-til)	696-704
ISSN	0021-9746
DOI	https://doi.org/10.1136/jclinpath-2019-205940
Status	Udgivet - 2019

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@article{7c4e1fcee10649f2b583c4d9d52eda96,

title = "Predictive value of AZGP1 following radical prostatectomy for prostate cancer: A cohort study and meta-analysis",

abstract = "Aims Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). Methods The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. Results Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). Conclusions Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.",

keywords = "cancer, immunohistochemistry, prostate",

author = "Gitte Kristensen and Berg, {Kasper Drimer} and Toft, {Birgitte Gr{\o}nk{\ae}r} and Stroomberg, {Hein Vincent} and Rosalie Nolley and Brooks, {James D.} and Klaus Brasso and Roder, {Martin Andreas}",

year = "2019",

doi = "10.1136/jclinpath-2019-205940",

language = "English",

volume = "72",

pages = "696--704",

journal = "Journal of Clinical Pathology",

issn = "0021-9746",

publisher = "B M J Group",

number = "10",

}

TY - JOUR

T1 - Predictive value of AZGP1 following radical prostatectomy for prostate cancer

T2 - A cohort study and meta-analysis

AU - Kristensen, Gitte

AU - Berg, Kasper Drimer

AU - Toft, Birgitte Grønkær

AU - Stroomberg, Hein Vincent

AU - Nolley, Rosalie

AU - Brooks, James D.

AU - Brasso, Klaus

AU - Roder, Martin Andreas

PY - 2019

Y1 - 2019

N2 - Aims Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). Methods The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. Results Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). Conclusions Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

AB - Aims Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). Methods The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. Results Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). Conclusions Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

KW - cancer

KW - immunohistochemistry

KW - prostate

U2 - 10.1136/jclinpath-2019-205940

DO - 10.1136/jclinpath-2019-205940

M3 - Journal article

C2 - 31331953

AN - SCOPUS:85072509746

SN - 0021-9746

VL - 72

SP - 696

EP - 704

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

IS - 10

ER -

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: A cohort study and meta-analysis

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