High-intensity focused ultrasound in prostate cancer: today's outcomes and tomorrow's perspectives.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.

INTRODUCTION: The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. PATIENTS AND METHODS: One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. RESULTS: Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded. CONCLUSIONS: In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control.

Hormono-radiotherapy in prostatic carcinoma: prognostic factors and implications for combined modality treatment.

The aim of this study was to evaluate the prognostic role of several clinical variables in a patient population undergoing neoadjuvant hormonotherapy (NHT) with external beam radiotherapy (ERT) to identify subsets of patients with an unfavorable prognosis who require intensified therapy. Eighty-four patients (mean age, 68.2 +/- 6.1 years; range, 52-81 years) underwent ERT (45 Gy to pelvic volume; 65 Gy mean dose to prostate volume) and NHT (oral flutamide: 250 mg three times daily for 30 days; LH-RH analogue: one vial every 28 days starting two months before radiotherapy and for its entire duration). The distribution according to clinical stage was T2: 46.4%, T3: 50.0%, T4: 3.6%. The distribution according to the Gleason score was grade 2-4: 17.9%; grade 5-7: 53.6%; grade 8-10: 28.5%. The distribution according to pretreatment PSA levels (in ng/mL) was 0-4: 5.9%; 4-10: 26.2%; 10-20:16.7%; > or = 20: 51.2%. With a median follow-up of 36 months, 3.6% of patients died; hematogenous metastases and local disease progression were found in 16.7% and 6% of patients, respectively. Overall, the incidence of disease progression was 17.9%. 32.9% of patients showed biochemical failure during followup. Overall, metastasis-free, local progression-free and biochemical failure-free actuarial survival at five years was 89.2%, 66.5%, 85.0% and 41.9%, respectively. At univariate analysis (log-rank) clinical stage (cT) was shown to be significantly correlated with the incidence of metastasis (P = 0.0004), local progression (P < 0.0001) and disease-free survival (P = 0.0005). At multivariate analysis (Cox) the correlations between clinical stage and metastasis (P = 0.0175), local progression (P = 0.0200) and disease-free survival (P = 0.0175) were confirmed. Gleason score and pretreatment PSA levels did not show any significant correlation with these endpoints. These results confirm the indications of the recent literature, which, in prostate carcinoma at higher clinical stages, suggest the use of prolonged hormonal therapy after radiotherapy.