Oncological outcome of neoadjuvant low-dose estramustine plus LHRH agonist/antagonist followed by extended radical prostatectomy for Japanese patients with high-risk localized prostate cancer: a prospective single-arm study.

BACKGROUND: Patients with advanced high-risk prostate cancer (PCa) are prone to have worse pathological diagnoses of positive surgical margins and/or lymph node invasion, resulting in early biochemical recurrence (BCR) despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether patients with high-risk PCa should undergo RP. The purpose of this study was to evaluate the efficacy of neoadjuvant chemohormonal therapy (NAC) followed by "extended" RP. METHODS: A total of 87 patients with high-risk PCa prospectively underwent extended RP after NAC; most of the patients underwent 6 months of estramustine phosphate (EMP) 140 mg twice daily, along with a luteinizing hormone-releasing hormone agonist/antagonist. We developed our surgical technique to reduce the rate of positive surgical margins. We aimed 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 was exposed. RESULTS: More than 1 year had elapsed after surgery in all 86 patients, with a median follow-up period of 37.7 months. The 3-year BCR-free survival was 74.9%. Multivariate Cox-regression analysis revealed that a positive core ratio of 50% or greater and pathological stage of pT3 or greater were independent predictors for BCR. About 17 of 23 cases received salvage androgen deprivation therapy and concurrent external beam radiotherapy, and showed no progression after the salvage therapies. CONCLUSIONS: NAC concordant with extended RP is feasible and might provide good cancer control for patients with high-risk PCa.

Radical Prostatectomy With and Without Neoadjuvant Chemohormonal Pretreatment for High-Risk Localized Prostate Cancer: A Comparative Propensity Score Matched Analysis.

BACKGROUND: To investigate the clinical outcomes in patients with high-risk prostate cancer (PCa) treated with neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP). PATIENTS AND METHODS: Our NCHT protocol involved complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) plus estramustine phosphate (560 mg). NCHT was provided to 60 patients with PCa before RP, and we compared the clinical and pathologic outcomes with those of 349 patients with high-risk PCa who underwent RP alone using propensity score matching. The data for those who underwent RP alone were obtained from the Michinoku Japan Urological Cancer Study Group database. RESULTS: In the NCHT group, 10.0% experienced pathologic complete response, 3.3% had positive surgical margins, and 13.3% developed severe complications (Clavien-Dindo grade III or higher) after RP. The median follow-up duration was 42.5 months, and the 5-year biochemical recurrence (BCR)-free survival was 60.1%. In multivariate analysis, pN+ was an independent prognostic factor for BCR (hazard ratio = 5.251, 95%CI 1.300-21.201; P = .020). In propensity score matching, the BCR rate in the NCHT group was significantly lower than that in the RP alone group (P = .021). In subgroup analyses, the BCR rate in patients with a single high-risk factor was significantly lower in the NCHT group than in the RP-alone group (P = .027). CONCLUSION: NCHT before RP can reduce the risk of BCR in patients with high-risk PCa, particularly if a single high-risk factor is present. However, the potential for perioperative complications should be considered.

Overall survival of high-risk prostate cancer patients who received neoadjuvant chemohormonal therapy followed by radical prostatectomy at a single institution.

BACKGROUND: The optimal treatment for high-risk prostate cancer (PCa) remains to be established. We previously reported favorable, biochemical recurrence-free survival in high-risk PCa patients treated with a neoadjuvant gonadotropin-releasing hormone agonist or antagonist and estramustine phosphate (EMP) (chemohormonal therapy; CHT) followed by radical prostatectomy (RP). We conducted a retrospective study to elucidate the clinical benefit of neoadjuvant CHT for high-risk PCa patients. METHODS: We reviewed the clinical and pathological records of 1254 PCa patients who underwent RP and bilateral pelvic lymphadenectomy between July 1996 and April 2016 at Hirosaki University. According to the D'Amico risk classification, we focused on 613 patients in the high-risk group. The high-risk PCa patients were further divided into two groups based on whether the patients received neoadjuvant CHT before RP (EMP group) or not (non-EMP group). The endpoint was overall survival (OS) after surgery. RESULTS: The 5- and 10-year OS rates were 98.5 and 92.6%, respectively. The 10-year OS rate in the EMP group was significantly higher compared to the non-EMP group (P = 0.021). In multivariate analysis, administration of neoadjuvant CHT, lymph node involvement, and castration-resistant PCa status were significantly associated with OS. CONCLUSIONS: RP with neoadjuvant CHT using EMP for high-risk PCa patients provided excellent long-term OS.

Efficacy of a neoadjuvant gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate in high-risk prostate cancer: a single-center study.

PURPOSE: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH + EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH + EMP) in patients with high-risk Pca. METHODS: Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant GnRH + EMP (GnRH group) and 270 received LHRH + EMP (LHRH group) before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The endpoint was the rate of pathological T0 status. RESULTS: The rates of pathological T0 status were 11.0 and 8.9% in the GnRH group and LHRH group, respectively (P = 0.490). The 2-year BRFS rates were 97.8% in the GnRH group and 87.8% in the LHRH group (P = 0.027). CONCLUSION: Our findings suggest that neoadjuvant GnRH antagonist + EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted.

Marked leukocytosis in response to estramustine phosphate in a hormone-refractory prostate cancer patient.

A 67-year-old man was refered to our institution with a complaint of elevated serum prostate-specific antigen (PSA) level (54 ng/mL). Diagnosis was adenocarcinoma of the prostate with a Gleason score of 9, with bone metastasis (stageD2). He was treated with maximal androgen blockade followed by estramustine phosphate (EMP) because of the progression to hormone-refractory prostate cancer (HRPC). Leukocytosis over 20000/µL was repeatedly observed at each administration of EMP. This is the first case report of leukocytosis in response to EMP in an HRPC patient. The present case suggests that EMP could modulate leukocyte differentiation in HRPC patients.

Combined use of oral estramustine phosphate and oral etoposide in patients with hormone refractory prostate carcinoma / 中华泌尿外科杂志

50% for more than 1 month as effective,and the efficacy for soft tissue metastases were classified as complete,partial remission,stabilization and progression.Results All patients were followed up for 6-24 months(mean,12 months) with the evaluation of efficacy and toxicity.PSA levels decreased by at least 50% in 6 of 12 cases(50%);it decreased from(63.9?47.3)ng/ml before treatment to(14.4?8.8)ng/ml after treatment,with a mean duration of response being 7.5 months(range,5-12 months).Partial remission of soft tissue metastases was obtained in 2 cases;the metastatic lesions were reduced from 4.0 cm?5.0 cm,(3.0cm?)(3.5) cm to 2.0 cm?2.0 cm,1.0 cm?1.5 cm,respectively,by the treatment,with response duration being 3 and 8 months,respectively.Toxicities were minimal with leukopenia at grade Ⅰ in 1 case,anemia at grade Ⅰ in 1,baldness at grade Ⅰ in 1,nausea at grade Ⅰ in 2 and impaired liver function at grade Ⅱ in 1.Conclusions The combination of oral estramustine phosphate and oral etoposide may be an effective and well-tolerated regimen in patients with HRPC.