title: Long-term follow-up of a neoadjuvant chemohormonal taxane-based phase II trial before radical prostatectomy in patients with non-metastatic high-risk prostate cancer.
abstract: OBJECTIVE
  To assess the feasibility and activity of a neoadjuvant treatment combining a luteinizing hormone-releasing hormone (LHRH)-analogue, estramustine and docetaxel before radical retropubic prostatectomy (RRP) in patients with high-risk prostate cancer.
  
  
  METHODS
  High-risk patients were defined as clinical stage > or =T3 and/or a prostate-specific antigen (PSA) level of > or =15 ng/mL, and/or biopsy a Gleason sum of > or =8. Patients received LHRH analogue treatment until the PSA nadir (a stable PSA level for two consecutive determinations) and then, continuing hormone therapy, a combined regimen of estramustine and docetaxel. Patients had RRP within a month of completing the neoadjuvant regimen. All patients were assessed for toxicity and surgical complications. A clinical response was defined as complete (CR, the disappearance of all palpable and radiological abnormalities and a decline in PSA level of > or =90%) or partial (PR, a decline in PSA level of half or more with stable or improved palpable and/or radiological abnormalities). A pathological response was defined as 'complete' (undetectable cancer), 'substantial' (residual cancer in < or =10% of the surgical specimen) or 'minimal' (residual cancer in >10% of the surgical specimen). The biomarkers p53, bcl-2, MIB1, erbB2 and factor VIII were also evaluated.
  
  
  RESULTS
  Of 22 patients enrolled between March 1999 and January 2002, 21 (mean age 63 years; mean PSA level 61 ng/mL; median biopsy Gleason sum 8) completed the neoadjuvant therapy. The clinical stage was organ-confined in three patients (15%); five (25%) had pelvic lymphadenopathy on computed tomography. The neoadjuvant treatment was well tolerated, with only one grade 2 toxicity (Eastern Cooperative Oncology Group grading). All PSA values decreased by >90% from baseline after hormonal therapy only, and the mean reduction from before to after chemotherapy was statistically significant (P = 0.001). Three patients (15%) had a CR, 16 (80%) had a PR and one (5%), with sarcomatoid tumour, had progression; 19 had non-nerve-sparing RRP and there were no major complications during or after RRP. The pathological assessment showed that one patient (5%) had no tumour (pT0) and six (32%) had a 'substantial' response. The overall rate of organ-confined disease was 58%, vs a mean 8% predicted likelihood from the Kattan nomogram. Five patients (26%) had positive surgical margins and four (21%) had positive lymph nodes. At a median follow-up of 53 months, eight patients (42%) were disease-free. Organ-confined disease (P = 0.022), residual cancer at pathology in < or =10% of the surgical specimen (P = 0.007) and no seminal vesicle invasion (P = 0.001) correlated with disease-free survival.
  
  
  CONCLUSIONS
  A neoadjuvant chemohormonal regimen before RRP is feasible and active in patients with high-risk prostate cancer. The rate of pathological organ-confined disease was higher than expected and responding patients had an 85% disease-free survival rate at 5 years.
authors.affiliation: Urological Clinic, Azienda Ospedale, Università di Padova, Padova, Italy.
authors.forename: Tomaso
authors.initials: T
authors.lastname: Prayer-Galetti
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacco
authors.forename: Francesco
authors.initials: F
authors.lastname: Pagano
authors.forename: Marina
authors.initials: M
authors.lastname: Gardiman
authors.forename: Antonio
authors.initials: A
authors.lastname: Cisternino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Betto
authors.forename: Paola
authors.initials: P
authors.lastname: Sperandio
authors.forename: Paolo
authors.initials: P
authors.lastname: Sperandio
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D012307:Risk Factors; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D017329:Triptorelin Pamoate / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D017329:Triptorelin Pamoate; D000077143:Docetaxel; D004961:Estramustine; D017430:Prostate-Specific Antigen