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Primary Prostate Cancer p53 Status Predicts CRPC Treatment Response

Deleterious TP53 mutations in primary prostate cancer are linked to the survival of patients undergoing abiraterone or enzalutamide therapy for castration-resistant disease
08 Jan 2018
Anticancer Agents;  Prostate Cancer;  Translational Research;  Basic Principles in the Management and Treatment (of cancer);  Therapy;  Biological Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: Research shows that assessing for deleterious mutations in primary prostate cancer tissue can predict overall survival (OS) and progression-free survival (PFS) of patients undergoing treatment for castration-resistant prostate cancer (CRPC).

“It is notable that outcomes of treatment with abiraterone/enzalutamide could be predicted as early as from the time of initial biopsy”, say Benjamin Maughan, from Johns Hopkins University School of Medicine in Baltimore, Maryland, USA, and co-workers.

They screened tissue from 101 patients for TP53 missense mutations and PTEN deletions using immunohistochemistry assays testing for nuclear accumulation of p53 protein and PTEN protein loss, respectively.

As reported in Prostate Cancer and Prostatic Diseases, 47.5% of patients showed PTEN loss in their primary tumour sample but this biomarker was not significantly associated with OS or PFS.

A total of 26.7% of patients tested positive for p53 nuclear accumulation; these individuals had a median OS of 16.7 months, a significantly shorter duration than the 31.2 months for those without the biomarker, giving a hazard ratio (HR) of 2.32. Median PFS was also significantly shorter with p53 accumulation, at 5.5 versus 10.9 months and a HR of 2.14.

In addition, 19.8% of patients had both p53 nuclear accumulation and PTEN loss. These patients had a median OS of 15.9 months, significantly shorter than the 30.4 months achieved by the 43 patients with neither alteration (HR=2.12). The corresponding PFS values were 3.8 and 10.8 months, giving a significant HR of 2.15.

Multivariate analysis, adjusting for factors such as visceral disease, bone pain, Gleason score and ECOG performance status, gave a significant HR for PFS of 2.15 for p53 nuclear accumulation, alongside haemoglobin level (HR=0.67) and albumin (HR=4.81). p53 nuclear accumulation was also associated with poorer OS, but the HR of 2.19 did not reach significance.

“p53 alterations (but not PTEN status) as determined by [immunohistochemistry] may represent an effective tissue-based biomarker of abiraterone/enzalutamide sensitivity in men with CRPC, and may be interrogated reliably from primary tumor tissue negating the need for metastatic biopsies to identify this information”, Benjamin Maughan and team conclude.

But they add: “These findings require independent external validation before being incorporated into clinical practice.”

Reference

Maughan BL, Guedes LB, Boucher K, et al. p53 status in the primary tumor predicts efficacy of subsequent abiraterone and enzalutamide in castration-resistant prostate cancer. Prostate Cancer Prostatic Dis; Advance online publication 4 January 2018. Doi: 10.1038/s41391-017-0027-4

Last update: 08 Jan 2018

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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