Androgen receptor gene amplification at primary progression predicts response to combined androgen blockade as second line therapy for advanced prostate cancer

Purpose: Amplification of the androgen receptor gene has been found in a th ird of hormone refractory prostate carcinomas. It is possible that amplific ation facilitates cell growth ability in low concentrations of androgens re maining in the serum after androgen deprivation therapy. We evaluate whethe r androgen receptor gene amplification at primary progression is associated with response to second line combined androgen blockade for prostate cance r. Materials and Methods: A total of 77 patients with prostate cancer were tre ated initially with androgen deprivation monotherapy followed by combined a ndrogen blockade after the first progression. After initiation of second li ne combined androgen blockade patients were followed every 3 months to eval uate treatment responses. Biopsies were taken from the prostate at the firs t progression under endocrine monotherapy. Androgen receptor gene copy numb er was determined by fluorescence in situ hybridization. Results: Androgen receptor gene amplification was found in 10 of the 77 cas es (13%) at the primary disease progression, and was associated with a favo rable response to second line combined androgen blockade. Only 1 of 34 (3%) patients classified as nonresponders had androgen receptor gene amplificat ion, whereas 9 of 41 (21%) classified as having either stable disease or re sponse had amplification (p = 0.016). Patients with androgen receptor gene amplification also had a decrease in prostate specific antigen more often a fter combined androgen blockade than those with no amplification (p = 0.079 ). However, androgen receptor gene amplification was not associated with pa tient survival after the first progression. Conclusions: Androgen receptor gene amplification detected in tumors progre ssing during androgen deprivation monotherapy is associated with favorable treatment response to second line combined androgen blockade. This finding suggests that at least some androgen receptor amplified tumors retain a hig h degree of dependency on residual androgens remaining in serum after monot herapy.