Androgen receptor gene amplification at primary progression predicts response to combined androgen blockade as second line therapy for advanced prostate cancer.
OBJECTIVE
Amplification of the androgen receptor gene has been found in a third of hormone refractory prostate carcinomas. It is possible that amplification facilitates cell growth ability in low concentrations of androgens remaining in the serum after androgen deprivation therapy. We evaluate whether androgen receptor gene amplification at primary progression is associated with response to second line combined androgen blockade for prostate cancer.


METHODS
A total of 77 patients with prostate cancer were treated initially with androgen deprivation monotherapy followed by combined androgen blockade after the first progression. After initiation of second line combined androgen blockade patients were followed every 3 months to evaluate treatment responses. Biopsies were taken from the prostate at the first progression under endocrine monotherapy. Androgen receptor gene copy number was determined by fluorescence in situ hybridization.


RESULTS
Androgen receptor gene amplification was found in 10 of the 77 cases (13%) at the primary disease progression, and was associated with a favorable response to second line combined androgen blockade. Only 1 of 34 (3%) patients classified as nonresponders had androgen receptor gene amplification, whereas 9 of 41 (21%) classified as having either stable disease or response had amplification (p = 0.016). Patients with androgen receptor gene amplification also had a decrease in prostate specific antigen more often after combined androgen blockade than those with no amplification (p = 0.079). However, androgen receptor gene amplification was not associated with patient survival after the first progression.


CONCLUSIONS
Androgen receptor gene amplification detected in tumors progressing 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 high degree of dependency on residual androgens remaining in serum after monotherapy.
Palmberg
C
C
Division of Urology, Tampere University Hospital, Finland.
Koivisto
P
P
Kakkola
L
L
Tammela
T L
TL
Kallioniemi
O P
OP
Visakorpi
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001706:Biopsy; D003131:Combined Modality Therapy; D018450:Disease Progression; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009919:Orchiectomy; D010865:Pilot Projects; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011944:Receptors, Androgen / Q000235:genetics*; D017211:Treatment Failure
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen