PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate.

Abstract

BACKGROUND:

Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.

OBJECTIVE:

To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.

DESIGN, SETTING, AND PARTICIPANTS:

We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.

RESULTS AND LIMITATIONS:

A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.

CONCLUSIONS:

Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.

PATIENT SUMMARY:

PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

• Authors: Roberta Ferraldeschi, Daniel Nava Rodrigues, Ruth Riisnaes, Susana Miranda, Ines Figueiredo, Pasquale Rescigno, Praful Ravi, Carmel Pezaro, Aurelius Omlin, David Lorente, Zafeiris Zafeiriou, Joaquin Mateo, Amelia Altavilla, Spyridon Sideris, Diletta Bianchini, Emily Grist, Khin Thway, Raquel Perez Lopez, Nina Tunariu, Chris Parker, David Dearnaley, Alison Reid, Gerhardt Attard, Johann de Bono
• Journal: European urology (Eur Urol) Vol. 67 Issue 4 Pg. 795-802 (Apr 2015) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 25454616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Androgen Antagonists
• Antineoplastic Agents
• PTEN Phosphohydrolase
• PTEN protein, human
• Abiraterone Acetate

Topics

• Abiraterone Acetate (therapeutic use)
• Aged
• Androgen Antagonists (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Disease-Free Survival
• Humans
• Male
• Middle Aged
• PTEN Phosphohydrolase (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, metabolism)
• Retrospective Studies
• Risk Factors
• Time Factors
• Treatment Outcome