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

Abstract

AimsZinc-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).MethodsThe 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.ResultsMedian 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).ConclusionsLow AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

AZGP1 Protein Expression in Hormone-Naïve Advanced Prostate Cancer Treated with Primary Androgen Deprivation Therapy

“…To the best of our knowledge, the present study is the first to analyze the predictive value of AZGP1 expression in patients with locally advanced or metastatic PCa commencing ADT. We found that patients with a low AZGP1 expression had a significantly higher rate of GS 9–10 and a higher cT-category than patients with a high AZGP1 expression, which is in accordance with previously published studies [ 8 , 9 , 10 ]. We found that the AZGP1 expression in tumor tissue is predictive of the time to CRPC.…”

“…Several studies have demonstrated that a low AZGP1 expression is an independent predictor of a shorter time to biochemical failure and initiating ADT, a shorter time to CRPC, and a greater risk of PCa-specific mortality for men undergoing radical prostatectomy [ 8 , 9 , 10 ]. A meta-analysis including 11,384 patients from eight different studies demonstrated that a low AZGP1 expression was associated with biochemical failure with a HR of 1.7 following radical prostatectomy [ 8 ].…”

“…Several studies have demonstrated that a low AZGP1 expression is an independent predictor of a shorter time to biochemical failure and initiating ADT, a shorter time to CRPC, and a greater risk of PCa-specific mortality for men undergoing radical prostatectomy [ 8 , 9 , 10 ]. A meta-analysis including 11,384 patients from eight different studies demonstrated that a low AZGP1 expression was associated with biochemical failure with a HR of 1.7 following radical prostatectomy [ 8 ]. Furthermore, previous research showed that adding AZGP1 expression levels resulted in a significant increase in the AUC from 78 to 83 and c-index from 0.618 to 0.662 in models predicting CRPC following radical prostatectomy [ 8 , 10 ].…”

“…The presence of intracellular AZGP1 immunoreactivity in biopsies was evaluated by one observer (M.D.W.). Each biopsy core was given a score from 0 to 3 based on the fraction of positive tumor cells and the intensity of cytoplasmic staining ( Figure 1 ) [ 15 ] using a previously described and standardized approach [ 8 , 16 ]. The immunohistochemical assessment was performed blinded to all clinical endpoints.…”

“…Zinc-alpha 2 glycoprotein (AZGP1) is an androgen-regulated biomarker in PCa with a potential prognostic impact. A meta-analysis has demonstrated that low AZGP1 expression in tumor tissue is an independent predictor of the time to biochemical failure following radical prostatectomy [ 8 ]. Furthermore, it was shown that AZGP1 is an independent predictor of time to CRPC and PCa-specific mortality following radical prostatectomy [ 8 , 9 , 10 ].…”