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Purpose: To determine whether neoadjuvant androgen deprivation therapy (NADT) improves clinical outcomes in patients with prostate cancer treated with definitive radiotherapy. Materials and Methods: We retrospectively reviewed medical records of 201 patients with prostate cancer treated with radiotherapy between January 1991 and December 2008. Of these, 156 patients with more than 3 years of follow-up were the subjects of this study. The median duration of follow-up was 91.2 months. NADT was given in 103 patients (66%) with median duration of 3.3 months (range, 1.0 to 7.7 months). Radiation dose was escalated gradually from 64 Gy to 81 Gy using intensity-modulated radiotherapy technique. Results: Biochemical relapse-free survival (BCRFS) and overall survival (OS) of all patients were 72.6% and 90.7% at 5 years, respectively. BCRFS and OS of NADT group were 79.5% and 89.8% at 5 years and those of radiotherapy alone group were 58.8% and 92.3% at 5 years, respectively. Risk group (p = 0.010) and radiation dose ≥70 Gy (p = 0.017) affected BCRFS independently. NADT was a significant prognostic factor in univariate analysis, but not in multivariate analysis (p = 0.073). Radiation dose ≥70 Gy was only an independent factor for OS (p = 0.007; hazard ratio, 0.261; 95% confidence interval, 0.071-0.963). Conclusion: NADT prior to definitive radiotherapy did not result in significant benefit in terms of BCRFS and OS. NADT should not be performed routinely in the era of dose-escalated radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: For locally advanced prostate cancer, the results of radiotherapy are improved by combination with androgen deprivation therapy. Volume reduction achieved with neoadjuvant hormonal treatment can facilitate dose escalation without increasing the toxicity. The optimal duration of hormonal treatment, however, is unknown. The endpoint of this study is the optimal duration of androgen deprivation for prostate volume reduction in a cohort of patients scheduled for external beam radiotherapy. Patients and methods: Twenty patients scheduled for external beam radiotherapy with cT2-3No/xMo prostate cancer were treated with a luteinizing hormone releasing hormone agonist (busereline) and nonsteroidal anti-androgen (nilutamide) for 9 months consecutively. Repeated CT scan examination was performed 3-monthly to measure prostate volumes until the start of radiation therapy. The analysis of volume reduction was performed with the Wilcoxon signed ranks test. Results: The baseline median prostate volume for the cohort of patients was 82 cc (95% CI: 61–104 cc) with a median volume reduction of 31% (95% CI: 26%–35%) (P < 0.0001) after 3 months of androgen deprivation. Between 3 and 6 months, a median volume reduction of 9% (95% CI: 4%–14%) (P < 0.0001) was observed. The effect was more pronounced in large prostates (>60 cc) than in small prostates (≤60 cc). In the total cohort of patients no significant volume reduction occurred between 6 and 9 months of maximal androgen blockade (MAB). Conclusions: In this study, we have shown that the most significant prostate volume reduction is achieved after 3 months of MAB with a maximum reduction after 6 months. Therefore, the optimal duration of neoadjuvant androgen deprivation to reduce prostate volume before prostate cancer radiotherapy is 6 months. In small prostates 3 months of hormonal treatment may be enough for maximal volume reduction. [ABSTRACT FROM AUTHOR]

Purpose: The shrinking effect of 3-month neoadjuvant androgen deprivation (NAD) on preradiotherapy prostate gland volume is well documented. However, recently, it has been shown that the cancerous prostate gland keeps shrinking up to 12 months after NAD start. Thus, if such a reduction is not taken into account, a larger than planned portion of the surrounding normal tissues might shift in the high-dose region during conformal radiotherapy (3DCRT) course. The present study was undertaken to quantify this issue.Materials and Methods: Prostate gland volume reduction between planning CT (plCT) and the last week of 3DCRT (tmtCT) was prospectively assessed in 33 consecutive patients with localized prostate carcinoma. The median time interval between plCT and tmtCT was 2.5 months (2.1–2.7 months). A single observer was asked to draw on each slice prostate gland volume as appropriate. The observer was ‘blind’ to the timing of CT (plCT vs. tmtCT). In order to estimate intra-observer variability, prostate gland delineation was repeated twice for each data set. Mean prostate gland change, plCT and tmtCT cumulative dose volume histogram (DVH) calculations for the rectum were analyzed for each patient. Results were correlated to AD status and its duration before plCT. Means were compared by non-parametric rank tests.Results: Based on an internal protocol, 14 patients (42%) did not receive AD, while 19 patients (58%) had undergone neoadjuvant and concomitant AD. The median duration of AD before plCT ranged from 0.2 to 6 months (median: 2.9 months). Although individual data were highly variable, compared to plCT volume, mean prostate gland volume change at the end of 3DCRT was similar for patients receiving (−7.3%) or not (−7%) androgen deprivation (P=0.77). However, within the group of patients treated with hormones, patients starting AD within 3 months from plCT had a significantly larger reduction in prostate volume (−14.2%) than patients with longer NAD duration (−1.1%, P=0.03). At tmtCT, on average, patients undergoing 3DCRT within 3 months from AD start showed an increase of the amount of rectum receiving 40–75 Gy compared to plCT values. At 40 Gy (V40) the mean difference between tmtCT and plCT was +7.5%. In the other two groups, average variations of V40–70 were within ±2% of plCT values. However, these differences are not significant.Conclusion: For patients who undergo plCT and 3DCRT shortly after AD start, prostate gland shrinkage may be substantial. In some of these patients, this might lead to an unexpected increase of the percentage of rectal wall exposed to intermediate doses. [Copyright &y& Elsevier]

Radical prostatovesiculectomy, radiation therapy, and complete androgen deprivation are acknowledged therapeutic concepts in the treatment of organ-confined prostate cancer. With cryoablation of the prostate, minimal invasive therapy has become available since 1991. Improvements in cryotechnique and progress in transrectal high-resolution ultrasound permit thermo-induced damage to the whole gland to be curative. Downstaging of prostate cancer by hormone ablative therapy remains a controversial issue at this time, but the use of androgen ablation decreases the size of the prostate gland which facilitates cryosurgery and improves the results. The freezing equipment has a limited capacity, and in certain instances large gland volumes prevent adequate freezing of the prostate. Since percutaneous prostate cryosurgery leaves dead tissue in situ to be resorbed over time, downsizing reduces the amount of necrotic tissue to be resorbed, reducing the potential for complications, particularly abscesses. The use of androgen ablation also increases the deposition of fat in the area of the Denonvillier’s fascia, making freezing of the rectum less likely during the procedure. In our study androgen ablative therapy was completed before performing cryosurgery in 26 of 43 patients (58%). The 17 patients not given androgen ablation therapy had gland volumes <40 ml, tumor volumes <3 ml, and no evidence of extracapsular tumor. The neoadjuvant therapy consisted of a 3- to 10-month course of leuprolide acetate combined with an antiandrogen. [ABSTRACT FROM AUTHOR]

Objective To measure the area distribution of epithelial and mesenchymal components in the prostate of patients with localized prostate cancer after temporary androgen deprivation. Patients and methods Surgical specimens from 38 patients treated with the gonadotrophin-releasing hormone agonist triptorelin for 3 months before radical prostatectomy were examined (group 1). Specimens from a second group of 54 patients who underwent the same surgical procedure with no prior therapy were used as controls (group 2). The specimens were serially step-sectioned and whole-mount tissue sections prepared. The epithelial, smooth muscle and connective tissue components were stained separately with immunohistochemical and histochemical techniques, respectively. Using colour-based image analyses, the tissue components were classified into three categories, displayed in different colours. The percentage of tumour areas occupied by cancer epithelial cells, connective tissue and smooth muscle was determined. Results In specimens from group 1, the cancer epithelium was sparse and scattered throughout the tumour area. A mean (sd) of 21 (11)% of the area was occupied by cancer cells, compared with 40 (11)% in the corresponding material from group 2 ( P<0.001). The connective tissue/smooth muscle ratio in stroma (about 1:1) was similar in both groups. Conclusions Neoadjuvant hormone treatment of patients with localized prostate cancer was associated with a marked reduction in tumour density and thus in the total amount of cancer epithelium. [ABSTRACT FROM AUTHOR]

Objective To examine the effect of pre-operative androgen deprivation on the progression rate of malignancy in patients operated on for localized prostate cancer. Patients and methods A total of 53 patients received no hormone therapy (group 1) and a further 38 patients (group 2) received the generic releasing-hormone agonist triptorelin during the 3 months before surgery. The patients in group 1 had T1b-T2 tumours, whereas 12 of those in group 2 had clinical stage T3 tumours. Despite this, the surgical specimens from the patients in group 2 showed a rate of cancer invasion of the surgical margins 20% lower than those from the patients in group 1. After prostatectomy, the patients were followed for 3 years by repeated analyses of prostate-specific antigen (PSA) in serum. Results During the follow-up, the PSA level exceeded the upper threshold (0.6 ng/mL) in 16 % of the patients in group 1 and in 43 % of those in group 2 ( P<0.05). This difference was mainly related to the pre-treatment stage of the tumour. Some of the patients in group 1 received post-operative radiotherapy but this was not reflected in their PSA levels. Of the patients in group 1 and 2, 4% and 14% respectively ( P>0.05), developed symptoms from skeletal metastases. Conclusion There was no evidence that pre-operative hormone therapy slowed the progression of prostate cancer. [ABSTRACT FROM AUTHOR]