title: Prolonged neoadjuvant combined androgen blockade leads to a further reduction of prostatic tumor volume: three versus six months of endocrine therapy.
abstract: OBJECTIVE
  In most clinical trials that have investigated the potential beneficial effects of neoadjuvant combined androgen blockade (CAB) in clinically localized prostate cancer, CAB has been given for 3 months, but no data are available on the influence of a longer duration of neoadjuvant CAB on the pathologic features of prostate cancer.
  
  
  METHODS
  Prostatectomy specimens of 40 patients, randomized to 3 (n = 18) or 6 (n = 22) months of neoadjuvant CAB, were blindly evaluated with regard to tumor volume, pathologic stage, and surgical margins. The morphologically most vital tumor areas were investigated for nucleolar size and MIB-1 defined proliferative activity.
  
  
  RESULTS
  The patients treated for 6 months had a median tumor volume 60% lower than the 3-month treatment group (P = 0.005). In the 6-month treatment group, no residual tumor could be found in 2 cases, but the proportion of prostatectomy specimens with seminal vesical invasion and positive surgical margins was not statistically different from that after 3 months. Compared with untreated controls, tumor proliferative activity assessed by MIB-1 immunoreactivity was significantly lower at 3 and 6 months of neoadjuvant CAB (P = 0.01). However, in 2 of 1 7 examined tumors that had been treated for 6 months, high MIB-1 scores suggested a development toward therapy-resistant cancer.
  
  
  CONCLUSIONS
  Prolonged neoadjuvant CAB for 6 months leads to a further decrease in prostatic tumor volume compared with the findings after 3 months. In a few instances, residual tumor areas with substantial MIB-1 defined proliferative activity persist at 6 months, thus indicating that in at least some cases, despite the overall decrease in tumor size, cancer cells can continue the cell cycle under CAB.
authors: Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
authors: T H
authors: TH
authors: van der Kwast
authors: B
authors: B
authors: Têtu
authors: B
authors: B
authors: Candas
authors: J L
authors: JL
authors: Gomez
authors: L
authors: L
authors: Cusan
authors: F
authors: F
authors: Labrie
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000726:Androgen Antagonists; D017329:Triptorelin Pamoate; C019176:Tryptal; D016729:Leuprolide