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

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. PATIENTS AND METHODS High‐risk patients were defined as clinical stage ≥T3 and/or a prostate‐specific antigen (PSA) level of ≥15 ng/mL, and/or biopsy a Gleason sum of ≥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 ≥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 ≤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 patient