Surgical and biologic outcomes after neoadjuvant bicalutamide treatment in prostate cancer.
OBJECTIVE
To perform a randomized, prospective, controlled, intention-to-treat study to determine the usefulness of bicalutamide as a neoadjuvant hormonal therapy regimen to surgery in reducing positive surgical margins and modulating epidermal growth factor receptor (EGFR) member's in men with prostate cancer.


METHODS
From April 2002 to December 2003, 430 men were diagnosed with prostate cancer. Of these men, 119 with clinical Stage T2-T3a were enrolled. Of the 119 men, 61 were assigned to receive 150 mg/day bicalutamide for 120 days before radical prostatectomy (bicalutamide plus surgery group) and 58 to radical prostatectomy alone (surgery group). Logistic regression analysis was performed to determine the relationship between bicalutamide and EGFR/Her2/neu levels. P <0.05 was considered to indicate significance.


RESULTS
Patients treated with bicalutamide had a 3.5-fold increase in negative surgical margins (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.4 to 8.74; P = 0.011). In particular, in Stage pT3a tumors, bicalutamide treatment was associated with a fivefold increase in negative surgical margins (OR 5.4; 95% CI 1.9 to 15.5; P = 0.002). In those with Stage pT2, no difference for this surgical outcome was noted. Immunohistochemical analysis revealed that bicalutamide increased EGFR levels 2.8-fold (OR 2.8; 95% CI 1.3 to 6.2; P = 0.014) and of 2.7-fold Her2/neu (OR 2.7; 95% CI 1.2 to 5.8; P = 0.022). When EGFR and Her2/neu were overexpressed, they were also active. In this regard, bicalutamide increased p-EGFR levels 3.3-fold (OR 3.3; 95% CI 1.3 to 8.2; P = 0.0016) and increased p-Her2/neu 2.8-fold (OR 2.8; 95% CI 1.2 to 6.3; P = 0.025).


CONCLUSIONS
Bicalutamide appears to reduce the prevalence of positive surgical margins. The upregulation of Her2/neu and EGFR and their phosphorylated forms was an early event after bicalutamide treatment. We hypothesized that the benefits of neoadjuvant hormonal therapy might be overwhelmed by the capacity of the residual tumor to acquire compensatory survival pathways and to grow and progress.
Gravina
Giovanni Luca
GL
Department of Urology, University of L'Aquila, Italy. giovanniluca.gravina@poste.it
Festuccia
Claudio
C
Galatioto
Giuseppe Paradiso
GP
Muzi
Paola
P
Angelucci
Adriano
A
Ronchi
Piero
P
Costa
Alessia Mariagrazia
AM
Bologna
Mauro
M
Vicentini
Carlo
C
D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000627:therapeutic use*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014105:Tosyl Compounds / Q000627:therapeutic use*; D015854:Up-Regulation
D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014105:Tosyl Compounds; C053541:bicalutamide