Poster Presentation 29th Lorne Cancer Conference 2017

A prospective multi-center Phase III validation study of AZGP1 as a biomarker in localised prostate cancer (#297)

Alison Y Zhang 1 2 , Judith Grogan 1 , Kate Mahon 1 3 , Krishan Rasiah 4 , Paul Sved 5 , David Eisinger 4 , John Boulas 4 , Arthur Vasilaris 4 , Susan Henshall 6 , Philip Stricker 1 7 , James Kench 1 8 , Lisa Horvath 1 2 3
  1. Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. University of Sydney, Darlington, NSW, Australia
  3. Chris O'Brien Lifehouse, Camperdown, NSW, Australia
  4. Department of Urology, North Shore Private Hospital, St Leonards, NSW, Australia
  5. Department of Urology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  6. Three Stories Consulting - Global Health Advocacy, New York, USA
  7. Department of Urology, St Vincent's Clinic, Darlinghurst, NSW, Australia
  8. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia

Background:

Prostate cancers with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of prostate cancer (PC) still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent Phase III cohort to evaluate the clinical utility of AZGP1 as a prognostic biomarker in localised PC.

 

Patients and methods:

In our multi-centre, prospective, Phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was dichotomized and assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous Phase II study. The primary endpoint was biochemical-relapse free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and prostate cancer specific survival (PCSS).  

 

Results:

In the Phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1 to 2.0; P = 0.02), MFS (HR, 3.2; 95% CI, 1.6 to 6.5; P = 0.001) and PCSS (HR, 4.1; 95% CI, 1.7 to 10.3; P = 0.002). These results were validated in our prospective Phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.8; 95% CI, 1.1 to 3.3; P =0.03), with shorter MFS (HR, 3.4; 95% CI, 1.3 to 9.2; P = 0.01).  

 

Conclusion:

Our study provides prospective Phase III validation that absent/low AZGP1 expression provides independent prognostic value in prostate cancer. This study provides robust evidence for the incorporation of this biomarker into clinical practice.