High Gleason score predicts poor pathologic outcome after neoadjuvant androgen deprivation for locally advanced prostate cancer

Patients with locally advanced prostate cancer are at high risk for having extraprostatic disease and adverse outcome after radical prostatectomy, whi ch makes neoadjuvant androgen deprivation (NAD) an attractive option, In th e present study, we tried to identify predictors of favorable pathologic ou tcome that will optimize patient selection for this therapeutic approach. S ixty-one patients with locally advanced prostate cancer were enrolled in a Phase II protocol involving 4 months of NAD followed by radical prostatecto my, Flutamide (250 mg orally three times per day for 20 days) and a luteini zing hormone-releasing (LHRH) analog (goserelin 3.6 mg or triptorelin 3.75 mg parenterally monthly) were given to the patients, and 59 of them complet ed the protocol, The main reason for recruitment was Stage T-3 disease (39 cases), serum prostate specific antigen (PSA) >30 ng/mL (12 cases), poorly differentiated tumors (2 cases), and 100% positive biopsy cores (6 cases). Favorable pathologic outcome was defined as a specimen-confined tumor (nega tive margins, absence of seminal vesicle/iliac lymph nodes involvement). In itial or pretreatment serum PSA, post-treatment serum PSA, initial clinical stage, and the percentage of positive biopsy cores could not predict the p athologic outcome after NAD, On the other hand, 66% of low-grade tumors (Gl eason score less than or equal to 6) and only 8% of high-grade tumors (Glea son score greater than or equal to 7 or any grade 4 component) showed a fav orable pathologic outcome. This difference was statistically significant (P = 0.0003), Patients with locally advanced prostate cancer and poorly diffe rentiated tumors only rarely show a favorable pathologic outcome after NAD, For this subset of patients, NAD prior to radical prostatectomy should not be offered with the aim of improving disease outcome.