AZGP1 in Localized Prostate Cancer Associated With Relapse Outcomes

Article

A prospective phase III validation study found that AZGP1 has significant prognostic utility as a biomarker in localized prostate cancer.

A prospective phase III validation study found that AZGP1 has significant prognostic utility as a biomarker in localized prostate cancer. Low or absent expression of the marker is associated with poorer biochemical relapse-free survival (BRFS), metastasis-free survival, and prostate cancer–specific survival (PCSS).

“Molecular biomarkers offer the potential for better risk assessment in prostate cancer,” wrote study authors led by Lisa G. Horvath, MBBS, PhD, of Chris O’Brien Lifehouse in Camperdown, Australia. “Although many putative biomarkers have been proposed in the literature, few have undergone validation and translation into clinical practice.”

The new study prospectively enrolled a phase III cohort with localized prostate cancer to test the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker. They included 347 samples from radical prostatectomy specimens, assayed by immunohistochemistry. The researchers also report final outcomes of a prior phase II study on this biomarker, published with the phase III results online ahead of print in Annals of Oncology.

The phase II cohort included 284 patients, 80 of whom (28%) had absent/low expression of AZGP1. After a median follow-up of 15.8 years, men with absent/low expression had a median BRFS of 25 months compared with 40 months for men with higher expression (P = .01). It was also associated with poor metastasis-free survival, with a multivariate analysis showing a hazard ratio (HR) for metastatic relapse of 2.8 (95% CI, 1.2–6.6; P = .02), and was a predictor of PCSS, with an HR of 3.8 (95% CI, 1.5–9.5; P = .005).

These results were confirmed in the larger phase III cohort. After a median follow-up of 6.4 years, the median BRFS was 56 months with absent/weak AZGP1 expression, compared with 70 months in others. A multivariate analysis showed a HR for biochemical relapse of 1.9 (95% CI, 1.1–3.3; P = .02).

For metastatic relapse, the HR with absent/low AZGP1 expression was 2 (95% CI, 1.1–3.4; P = .02). There were only five prostate cancer deaths so far in this cohort; on a univariate analysis, absent/low expression of the biomarker was associated with poorer PCSS, with an HR of 10 (95% CI, 1.1–89.7; P = .03); a multivariate analysis was not performed due to the low number of events.

The researchers found that incorporating AZGP1 expression into existing risk models improved the C-indexes for those models, meaning their prognostic ability is better when the biomarker is included.

“Our study demonstrates that AZGP1 is a reproducible predictor of biochemical and metastatic relapse in patients with localized prostate cancer with radical prostatectomy,” the authors concluded. “Data from our prospective phase III cohort suggests that AZGP1 should now become part of clinical pathology practice.”

Recent Videos
A phase 1 trial assessed the use of PSCA-directed CAR T cells in patients with metastatic castration-resistant prostate cancer.
Findings from a phase 1 study may inform future trial designs intended to yield longer responses with PSCA-targeted CAR T cells.
A phase 1 trial assessed the use of PSCA-directed CAR T cells in patients with metastatic castration-resistant prostate cancer.
Ongoing research may clarify the potential benefit of avelumab when administered in combination with other agents in advanced urothelial carcinoma.
Spatial analyses may help determine factors that influence responses to sacituzumab govitecan-containing regimens in urothelial carcinoma.
Attending educational sessions may help with understanding how to manage toxicities associated with enfortumab vedotin in rare genitourinary cancers.
Two women in genitourinary oncology discuss their experiences with figuring out when to begin a family and how to prioritize both work and children.
Over the past few decades, the prostate cancer space has evolved with increased funding for clinical trial creation and enrollment.