Multicenter phase II study of combined neoadjuvant docetaxel and androgen ablation (ADT) prior to radical prostatectomy (RP) for patients (pts) with high risk localized prostate cancer (LCaP): Pathologic outcomes and 3-year follow-up analyses
5002 Background: Pts with high risk LCaP (cT3, Gleason score > 7 &/or PSA > 20) have an increased risk of relapse with a biochemical failure rate of >50% at 3 years after RP. Docetaxel is active in hormone refractory prostate cancer & potentially beneficial if combined with ADT for treatment naïve disease. The objectives of this trial were to assess the pathologic outcomes & feasibility of docetaxel + ADT in men with LCaP prior to RP. Methods: A phase II multi-center study of newly diagnosed previously untreated pts with clinically LCaP with high-risk features. All pts received ADT (buserelin acetate 6.3 mg q8 weeks x 3 and anti-androgen for 4 weeks) plus docetaxel (35 mg/m2 weekly for 6 out of 8 weeks for 3 cycles) prior to RP. Results: 72 men with a median age of 59 years (range 46–78) were enrolled at 6 sites. Baseline characteristics included: clinical stage T1C, T2 & T3 in 14%, 47% & 39%; and Gleason score <7, 7 & >7 in 10%, 30% & 60% of pts; respectively. Median baseline PSA was 10.8 μg/L (range 1.6–65.6) with PSA < 10 in 47%, 10–20 in 24% & >20 in 29% of pts. Eight pts did not complete protocol therapy because of toxicity (n=4), withdrawal of consent (n=1), or other reasons (n=3). 1 pt had myocardial infarction day 1 post-operatively & 1 pt had DVT 1.5 months after RP. No other major post-operative complications were reported. Of the 64 pts completing protocol therapy, 2 had a complete pathologic response and pathologic stage was T2 in 34 (53%) and T3 in 28 (44%) pts. Four pts had N1 disease & positive surgical margins were identified in 17 (27%). On multivariate Cox regression analysis only baseline Gleason score (=7 vs. >7) was associated with PSA recurrence-free survival (hazard ratio 4.58, 95% CI 1.32–15.93). At a median follow-up of 42.7 months (range 25.6–65.6), 19 (30%) pts have relapsed. Three pts have died at 32.0, 40.0 & 40.3 months, with all deaths attributed to prostate cancer. Conclusions: Combined ADT and docetaxel prior to RP was feasible and resulted in encouraging pathologic outcomes and PSA- recurrence free survival. These data further support the rationale for randomized trials determining the efficacy of chemo-hormonal therapy in pts with clinically LCaP. [Table: see text]