Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.
OBJECTIVE
The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19).


METHODS
Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied.


RESULTS
Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG > or =19 that received H + RT (P = 0.028).


CONCLUSIONS
Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.
Abdel-Wahab
May
M
Department of Radiation Oncology, University of Miami School of Medicine, Miami, FL 33136, USA. mwahab@med.miami.edu
Berkey
Brian A
BA
Krishan
Awtar
A
O'Brien
Tom
T
Hammond
Elizabeth
E
Roach
Mack
M
Lawton
Colleen
C
Pilepich
Milijenko
M
Markoe
Arnold
A
Pollack
Alan
A
D000726:Androgen Antagonists / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy*; D011944:Receptors, Androgen / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome; D018911:Trinucleotide Repeats
D000726:Androgen Antagonists; D011944:Receptors, Androgen; D017273:Goserelin