L’articolo contenente la descrizione dei dati all’arruolamento dello studio Pros-IT CNR è stato accettato per la pubblicazione dalla rivista “Health and Quality of Life Outcomes”
Su “Le Scienze” del 30 giugno 2016 è stato pubblicato l’articolo “CNR – Tumore alla prostata: i primi dati dello studio Pros-IT”.
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AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
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.
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.
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.
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.).
The objective of this paper is to review the current recommendations for active surveillance in prostate cancer from the present prospective studies. Worldwide, there are increasing numbers of men with prostate cancer. It is now accepted as standard care that a number of men with favorable-risk disease can be followed with active surveillance. In 1995, the first prospective studies were initiated to assess the feasibility of active surveillance, in which the decision to intervene was determined by prostate-specific antigen and/or histological progression. The strategy was to provide therapy individualized to the biological behavior of the cancer. Clinical trials assessing active surveillance have usually included patients younger than 70 years of age, although the guidelines have changed over time for Gleason score and prostate-specific antigen, eg, doubling time, thereby changing the indication for active treatment. The present review focuses on patient selection, prospective studies reported in the literature, and future directions.
Recent advances need to be highlighted in the management of both localized and metastatic prostate cancer. New early detection and molecular characterization tools are being developed to improve differentiation of their progression profiles and reduce “overdetection” and “overtreatment” of clinically “insignificant” cancers. In addition, the development of multi-parametric MR has improved the characterization of localized cancer and introduced the new concept of focal treatment. Finally, several treatments for metastatic cancer which is resistant to castration have recently increased the therapeutic armamentarium.