SIUrO press 03/07/14 – Al via la prima grande indagine epidemiologica sul tumore della prostata

http://www.siuro.it/en/siuro-press

03/07/14 – Al via la prima grande indagine epidemiologica sul tumore della prostata  

Intervista al dott. Giario Conti, Direttore Unita operativa di urologia, Ospedale S. Anna di Como, presidente della Società Italiana di Urologia Oncologica (SIUrO).

Scattare una fotografia del cancro della prostata in Italia: quanti sono  i malati, quali le cure e i centri dove si può ricevere assistenza.  E’ questo l’obiettivo di un progetto denominato PROS-IT appena presentato a Bologna in occasione del 24° congresso nazionale della Società italiana di urologia oncologica (SIUrO).

Unica nel suo genere in Italia, l’iniziativa è resa possibile da un educational grant di Takeda farmaceutici ed è coordinata dalla Sezione invecchiamento dell’Istituto di neuroscienze (In-Cnr).

Ne abbiamo parlato con il dott. Conti che abbiamo incontrato a Bologna:  G. Conti Pros-IT

AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer

N Engl J Med. 2014 Sep 11;371(11):1028-38. doi: 10.1056/NEJMoa1315815. Epub 2014 Sep 3.

AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.

Abstract

BACKGROUND:

The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone.

METHODS:

We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospectively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status (positive vs. negative) and prostate-specific antigen (PSA) response rates (the primary end point), freedom from PSA progression (PSA progression-free survival), clinical or radiographic progression-free survival, and overall survival.

RESULTS:

A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of whom 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells. Among men receiving enzalutamide, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 53%, P=0.004) and shorter PSA progression-free survival (median, 1.4 months vs. 6.0 months; P<0.001), clinical or radiographic progression-free survival (median, 2.1 months vs. 6.1 months; P<0.001), and overall survival (median, 5.5 months vs. not reached; P=0.002). Similarly, among men receiving abiraterone, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 68%, P=0.004) and shorter PSA progression-free survival (median, 1.3 months vs. not reached; P<0.001), clinical or radiographic progression-free survival (median, 2.3 months vs. not reached; P<0.001), and overall survival (median, 10.6 months vs. not reached, P=0.006). The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length androgen receptor messenger RNA.

CONCLUSIONS:

Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone. These findings require large-scale prospective validation. (Funded by the Prostate Cancer Foundation and others.).