title: Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer.
abstract: 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.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str, 22, Munich 81675, Germany. mark.thalgott@lrz.tum.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Thalgott
authors.forename: Thomas
authors.initials: T
authors.lastname: Horn
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Heck
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.forename: Matthias
authors.initials: M
authors.lastname: Eiber
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Michael
authors.initials: M
authors.lastname: Autenrieth
authors.forename: Kathleen
authors.initials: K
authors.lastname: Herkommer
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Krause
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Gschwend
authors.forename: Uwe
authors.initials: U
authors.lastname: Treiber
authors.forename: Hubert R
authors.initials: HR
authors.lastname: Kübler
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D043823:Taxoids; D000077143:Docetaxel