Long-term neoadjuvant hormone therapy prior to radical prostatectomy: Analysis of outcome by preoperative risk factors

A prospective Phase II trial was initiated to assess the effects of 8 month s of neoadjuvant hormone therapy on pathologic stage and biochemical recurr ence rates. A total of 158 men with clinically localized prostate cancer we re treated with neoadjuvant combined androgen withdrawal for 8 months prior to radical prostatectomy. Preoperative clinical stage, Gleason score, and serum prostate specific antigen (PSA) were examined for influence on treatm ent outcome (pathologic stage and PSA recurrence). At diagnosis, PSA was <1 0 mu g/L in 64%, 10 to 20 mu g/L in 21%, and >20 mu g/L in 15% (mean 11.5 m u g/L). The clinical stage was T-1c in 17%, T-2a in 24%, T-2b in 52%, and T -3a in 7%. The gleason score was less than or equal to 4 in 31%, 5 or 6 in 47%, and greater than or equal to 7 in 22%. The pathologic stage was T-0 in 11%, T-2 (organ confined) in 68%, T-3 (specimen-confined) in 13%, T-3 (mar gin positive) in 5%, and TxN+ in 2%. High-risk factors (Stage T-3a, Gleason greater than or equal to 7, or PSA greater than or equal to 10 mu g/L) wer e present in 49% of patients. The risk of positive-margin disease increased with Stage T-3a v organ-confined disease (25% v 4%), with pretreatment Gle ason scores greater than or equal to 7 v <7 (11% v 4%), and with pretreatme nt PSA greater than or equal to 10 mu g/L v <10 mu g/L (15% v 0). The overa ll recurrence rate detected by PSA was 10% after a mean postoperative follo w-up of 33 months. The risk of PSA recurrence increased with clinical stage (18% T-3 v 10[% organ-confined), pretreatment PSA (5% when PSA was <10 mu g/L v 17% when PSA was greater than or equal to 10 mu g/L), Gleason score ( 8% when less than or equal to 6 v 16% when greater than or equal to 7), and pathologic stage (3% of pT(2), 25% of pT(3) margin negative and 50% of pT( 3) margin positive). Recurrences identified by PSA occurred in 5% of patien ts with no adverse preoperative risk factors, 16% of those with any one of the high-risk factors, and 23% of those with any two of the high-risk facto rs. Eight months of neoadjuvant therapy results in low positive-margin rate s and a low overall risk of biochemical recurrence. The risk of PSA recurre nce remains proportional to the number of adverse preoperative risk factors . Randomized studies are required to determine whether a longer duration of neoadjuvant therapy will reduce the biochemical recurrence rate.