Possible Risk Factors Associated with Relapse in Patients Treated with Neoadjuvant Chemohormonal Therapy for High Risk Prostate Cancer

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 (P=0.03). 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.