Histologic basis and optimal duration for neoadjuvant androgen deprivationtherapy

Patients with one or more positive margins at radical prostatectomy have an increased incidence of disease recurrence. The US Group T2b Study demonstr ated a reduction of resection-margin involvement from 48% to 18% after 3 mo nths of neoadjuvant hormone-deprivation therapy (NHT). However, at 36 month s' followup, there was no significant difference in the biochemical (prosta te specific antigen; PSA) recurrence rate. A subgroup analysis from this st udy indicated that patients whose tumors had high Gleason scores (8-10) had a lower biochemical relapse rate if they received 3 months of NHT before s urgery, 39% v 65%. Therefore, if inductive NHT is beneficial, selection of patients likely to have positive margins might be a more efficient way to u tilize neoadjuvant therapy. Eight months of neoadjuvant therapy has been re ported by others to reduce the positive-margin incidence to 6%. Patients me re selected on the basis of PSA >10 ng/mL; Gleason score greater than or eq ual to 7, and involvement of four or more core biopsies as more likely to h ave tumor extension beyond the prostate capsule and more likely to benefit from NHT. Those 27 patients received combined LHRH agonist and antiandrogen for 4 to 14 months (average 5.7 months) prior to radical prostatectomy. Ra dical prostatectomies showed the maximum histologic androgen-deprivation ef fect after 6 months of NHT, with greater tumor apoptosis and necrosis, muci n lakes, collagen nodules, inflammation, and periprostatic fibrosis. In 55% of the patients with >6 months of NHT, the tumor volume was <5% of the cut surface. Only 18% of patients had one or more positive margins, but 18% ha d seminal vesicle involvement, and one had lymph node metastasis. No advers e clone selection was observed with immunostaining for the Ki-67 proliferat ive cell marker. Only an 18% rate of positive margins was observed in patie nts preselected as unlikely to have organ-confined disease. With a mean fol low-up of 18 (range 8-72) months, there was a 26% biochemical recurrence ra te. Two patients received postoperative radiation, and five have remained o n hormonal therapy. All patients are alive.