Objectives: To perform a pilot hypothesis generating study of neoadjuvant docetaxel, estramustine, and
androgen deprivation therapy for high-risk patients prior to radical prostatectomy.
Patients and Methods: Twenty-eight patients received 4 cycles of docetaxel and estramustine administered on an every
three week schedule in combination with androgen deprivation therapy (LHRH analog and bicalutamide) prior to radical
prostatectomy. Following the prostatectomy, androgen deprivation therapy was continued for 8 months. End-points were
pathological complete response (pCR), time-to-relapse (TTR), feasibility and tolerability, and biochemical or clinical
correlates of relapse.
Results: With a median of 80 months (6.6 years) of follow-up, 18/28 patients have relapsed and one patient died from
unrelated causes while in remission, with median TTR of 44 months (3.6 years). Tumor downstaging, perhaps as a result
of neoadjuvant therapy, was associated with a decreased risk of relapse (P=0.0002). Consistent with this result, positive
margin status was associated with an increased risk of relapse, which was not affected by adjuvant radiation therapy.
Increased expression of a possible tumor stem cell marker, (Sry-related high mobility group box-9) Sox-9, both at the time
of prostatectomy (P=0.005) and in the pre-treatment tumor biopsy cores was associated with an increased risk of relapse
Conclusions: The neoadjuvant chemohormonal regimen may have benefited some patients, especially those who
exhibited pathologic downstaging. Sox-9 expression in prostate cancer specimens warrants prospective validation in both
pre-prostatectomy tissue as well as patients undergoing an ongoing randomized trial using a similar neoadjuvant regimen.