An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy

Alison Y. Zhang, Karen Chiam, Ygal Haupt, Stephen Fox, Simone Birch, Wayne Tilley, Lisa M. Butler, Karen Knudsen, Clay Comstock, Krishan Rasiah, Judith Grogan, Kate L. Mahon, Tina Bianco-Miotto, Carmela Ricciardelli, Maret Böhm, Susan Henshall, Warick Delprado, Phillip Stricker, Lisa G. Horvath, James G. Kench

Research output: Contribution to journalArticle

Abstract

A plethora of individual candidate biomarkers for predicting biochemical relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with biochemical relapse. In the current study, these biomarkers were re-analyzed for biochemical relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n = 324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with biochemical relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95% CI, 1.6–32; p = 0.01) and multivariable analysis (HR 5.4, 95% CI, 1.2–25; p = 0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p < 0.001). Our findings indicate that biochemical relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.

LanguageEnglish
Pages1151-1159
Number of pages9
JournalInternational Journal of Cancer
Volume144
Issue number5
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • AZGP1
  • Ki67
  • biomarkers
  • prognosis
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, Alison Y. ; Chiam, Karen ; Haupt, Ygal ; Fox, Stephen ; Birch, Simone ; Tilley, Wayne ; Butler, Lisa M. ; Knudsen, Karen ; Comstock, Clay ; Rasiah, Krishan ; Grogan, Judith ; Mahon, Kate L. ; Bianco-Miotto, Tina ; Ricciardelli, Carmela ; Böhm, Maret ; Henshall, Susan ; Delprado, Warick ; Stricker, Phillip ; Horvath, Lisa G. ; Kench, James G. / An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy. In: International Journal of Cancer. 2019 ; Vol. 144, No. 5. pp. 1151-1159.
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abstract = "A plethora of individual candidate biomarkers for predicting biochemical relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with biochemical relapse. In the current study, these biomarkers were re-analyzed for biochemical relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n = 324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with biochemical relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95{\%} CI, 1.6–32; p = 0.01) and multivariable analysis (HR 5.4, 95{\%} CI, 1.2–25; p = 0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p < 0.001). Our findings indicate that biochemical relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.",
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Zhang, AY, Chiam, K, Haupt, Y, Fox, S, Birch, S, Tilley, W, Butler, LM, Knudsen, K, Comstock, C, Rasiah, K, Grogan, J, Mahon, KL, Bianco-Miotto, T, Ricciardelli, C, Böhm, M, Henshall, S, Delprado, W, Stricker, P, Horvath, LG & Kench, JG 2019, 'An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy', International Journal of Cancer, vol. 144, no. 5, pp. 1151-1159. https://doi.org/10.1002/ijc.31906

An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy. / Zhang, Alison Y.; Chiam, Karen; Haupt, Ygal; Fox, Stephen; Birch, Simone; Tilley, Wayne; Butler, Lisa M.; Knudsen, Karen; Comstock, Clay; Rasiah, Krishan; Grogan, Judith; Mahon, Kate L.; Bianco-Miotto, Tina; Ricciardelli, Carmela; Böhm, Maret; Henshall, Susan; Delprado, Warick; Stricker, Phillip; Horvath, Lisa G.; Kench, James G.

In: International Journal of Cancer, Vol. 144, No. 5, 01.03.2019, p. 1151-1159.

Research output: Contribution to journalArticle

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T1 - An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy

AU - Zhang, Alison Y.

AU - Chiam, Karen

AU - Haupt, Ygal

AU - Fox, Stephen

AU - Birch, Simone

AU - Tilley, Wayne

AU - Butler, Lisa M.

AU - Knudsen, Karen

AU - Comstock, Clay

AU - Rasiah, Krishan

AU - Grogan, Judith

AU - Mahon, Kate L.

AU - Bianco-Miotto, Tina

AU - Ricciardelli, Carmela

AU - Böhm, Maret

AU - Henshall, Susan

AU - Delprado, Warick

AU - Stricker, Phillip

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AU - Kench, James G.

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