Background: Patients with high-risk prostate cancer (PCa) according to D’Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether RP should be done for high risk PC patients. Methods: 87 high-risk PCa patients prospectively underwent ‘extended’ RP following neoadjuvant chemohormonal therapy (NAC); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D’Amico risk categories Results: More than 1 year had elapsed after surgery in 69 of the 87 patients with the median follow-up period of 36.2 months. Among those 69 patients, 18 (26.1%) experienced PSA failure. Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with higher positive biopsy core ratio, lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure. These 18 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 34.6 months after PSA progression). Conclusions: NAC concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa.