Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer

Background: Patients with locally advanced and high-risk prostate cancer (LAPC) are prone to experience biochemical recurrence despite radical prostatectomy (RP). We evaluated feasibility, safety and activity of a neoadjuvant chemohormonal therapy (NCHT) with 3-weekly full dose docetaxel and complete androgen blockade (CAB) in locally advanced and high-risk prostate cancer patients (LAPC) undergoing RP. Methods. Patients (n = 30) were selected by Kattans' preoperative score and received trimestral buserelin 9,45 mg, bicalutamide 50 mg/day and 3 cycles docetaxel (75 mg/m²) followed by RP. Primary endpoints were biochemical (PSA) and local downstaging. Secondary endpoints included toxicity and operability assessments, pathological complete response (pCR), time to PSA progression, 5-year biochemical recurrence free survival (bRFS) and overall survival (OS). Results: Median baseline PSA was 25.8 ng/ml (2.1-293), and the predicted probability of 5-year bRFS was 10% (0-55). NCHT induced PSA-reduction was 97.3% (81.3-99.9%; p < 0.001) and post-RP 96.7% of patients were therapy responders, with undetectable PSA-values. Post- vs. pretreatment MRI indicated a median tumor volume reduction of 46.4% (-31.3-82.8; p < 0.001). A pathological downstaging was observed in 48.3%. Severe hematologic toxicities (≥CTC3) were frequent with 53.8% leucopenia, 90% neutropenia and 13.3% febrile neutropenia. RP was performed in all patients. While resectability was hindered in 26.7%, continence was achieved in 96.7%. Pathologic analyses revealed no pCR. Lymph node- and extracapsular involvement was observed in 36.7% and 56.7% with 33.3% positive surgical margins. After a median of 48.6 (19.9-87.8) months, 55.2% of therapy responders experienced PSA-recurrence. The estimated median time to PSA-progression was 38.6 months (95%CI 30.9-46.4) and 85.3 months (95%CI 39.3-131.3) for OS. The 5-year bRFS was improved to 40%, but limiting for interpretation adjuvant treatment was individualized. Conclusions: NCHT is feasible despite high hematotoxicity, with excellent functional results. Significant downstaging was observed without pCR. NCHT seems to improve the cohort adjusted 5-year bRFS, but clinical value needs further investigation in randomized trials.