logo

Rate this article:

Article of the week: Androgen receptor (AR) splice variant 7 and full‐length AR expression is associated with clinical outcome: a translational study in patients with castrate‐resistant prostate cancer




695 views

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Androgen receptor (AR) splice variant 7 and full‐length AR expression is associated with clinical outcome: a translational study in patients with castrate‐resistant prostate cancer

Marzia Del Re*, Stefania Crucitta*, Andrea Sbrana, Eleonora Rofi*, Federico Paolieri, Giulia Gianfilippo*, Luca Galli, Alfredo Falcone, Riccardo Morganti, Camillo Porta§¶, Eleni Efstathiou**, Ron van Schaik††, Guido Jenster‡‡ and Romano Danesi*

*Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, Section of Statistics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, §Department of Internal Medicine, University of Pavia, Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy, **Division of Cancer Medicine, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Centre, Houston, TX, USA, ††Department of Clinical Chemistry, and ‡‡Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands

Read the full article

Abstract

Objectives

To investigate if full‐length androgen receptor (AR‐FL) is associated with resistance to androgen receptor (AR)‐directed therapy independently and/or combined with AR splice variant 7 (AR‐V7).

Patients and Methods

Plasma samples were prospectively collected from 73 patients with castrate‐resistant prostate cancer before first‐ or second‐line AR‐directed therapy. mRNA was isolated from exosomes and AR‐FL and AR‐V7 were analysed by droplet digital PCR.

Fig. 6. Proposed flow‐chart of clinical decision making based on androgen receptor (AR) analysis. The AR‐V7‐negative patients for whom the knowledge of full‐length AR (AR‐FL) expression levels allows a better definition of therapeutic approach are highlighted in red. Abi, abiraterone; CRPC, castrate‐resistant prostate cancer; Enza, enzalutamide.

Results

AR‐FL was detected in all patients and 22% of them were AR‐V7‐positive at baseline. AR‐FL expression was significantly higher in AR‐V7‐positive vs AR‐V7‐negative patients (P < 0.0001). After stratifying patients by tertile for AR‐FL expression, progression‐free survival (PFS) was 22 vs 18 vs 4 months for lower vs intermediate vs higher tertile, respectively (P = 0.0003). The median PFS and overall survival were significantly longer in AR‐V7‐negative vs AR‐V7‐positive patients (20 vs 4 months, P < 0.0001; not reached vs 9 months, P < 0.0001, respectively).

Conclusions

Resistance to AR‐directed therapy was associated with the presence of AR‐V7; however, AR‐FL expression may help better refine response and survival of patients to AR‐directed therapy. Both biomarkers, if validated in prospective trials, could be used to select the best treatment strategy.

Read more Articles of the week

Join the Discussion

*

Please note that all submitted comments will be reviewed by the BJUI Web Team before they are considered for publishing on the site. Comments may take up to 48 hours to go live. If you have made a comment which has not appeared live after this time and you wish to discuss this matter further, please contact us.