Biochemical and Pathological Effects of 8 Months of Neoadjuvant Androgen Withdrawal Therapy Before Radical Prostatectomy in Patients with Clinically Confined Prostate Cancer
Accepted 14 July 1995.
Abstract
Purpose
A prospective, nonrandomized trial was initiated to determine the duration of neo-adjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram/l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining.
Materials and Methods
We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly.
Results
Serum PSA decreased by 84 percent after 1 month and by a further 52 percent between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram/l.) or reached its nadir in 22 percent of the cases after 3 months, 42 percent after 5 months and 84 percent after 8 months. Overall, the positive margin rate was 4 percent. Of the cases 68 percent were organ-confined and 24 percent were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy.
Conclusions
Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.
Departments of Surgery and Pathology, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, Canada.
Supported in part by Grant 6-73535 from the National Cancer Institute of Canada and Lotte and John Hecht Memorial Fund.
ABSTRACT