THE INDICATIONS, RATIONALE, AND RESULTS OF NEOADJUVANT ANDROGEN DEPRIVATION IN THE TREATMENT OF PROSTATIC-CANCER - MEMORIAL-SLOAN-KETTERING-CANCER-CENTER RESULTS

Objectives. The use of neoadjuvant chemotherapy prior to definitive su rgery has been firmly established in other areas of oncology, most not ably in the treatment of testis and Wilm's tumors. The use of neoadjuv ant androgen deprivation therapy (ADT) in conjunction with radical pro statectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperati ve ADT (goserelin and flutamide) on the pathologic staging and postsur gery prostate-specific antigen (PSA) relapse rate. We also reviewed th e data confirming the understaging of clinically localized prostatic c ancer and the experimental data providing the conceptual support for A DT. Methods. We report the results of 141 patients, Stage TO-TO, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone. Results. The 69 patients who receiv ed 3 months of goserelin and flutamide followed by radical prostatecto my had a pathologic organ-confined cancer rate of 74%, versus 48% in t he control group who received no ADT prior to surgery. The margin-posi tive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-c onfined and margin-positive rates were 73% and 17% in the ADT group ve rsus 56% and 36% in the control arm, respectively. The PSA disease-fre e rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) w as 89% in the ADT-treated patients (N = 98) and 84% in the control pat ients (N = 96). There was no statistical difference demonstrated betwe en the arms with respect to biochemical failure. Conclusions. While th e pathologic staging of tumors following ADT treatment was improved co mpared with surgical controls, to date the PSA disease-free survival r ates are similar. Patients with residual extracapsular (P3) disease af ter ADT manifest an increased PSA failure rate compared with those wit h P3 tumors treated by surgery alone. This suggests that ADT may ident ify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occu rs. (C) 1997 by Elsevier Science Inc.