Treatment of localized prostate cancer using high-intensity focused ultrasound

OBJECTIVE: To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. PATIENTS AND METHODS: In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively. RESULTS: The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01-20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21-1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. CONCLUSION: HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.     

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.     

First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer

OBJECTIVE: To evaluate the long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for patients with localised prostate cancer. MATERIAL AND METHODS: Patients included in this multicentre analysis had T1-T2 NxM0 prostate cancer, a PSA<15 ng/ml, and a Gleason score (GS) < or = 7, and were treated with prototypes or first-generation Ablatherm HIFU devices between October 1997 and August 2001. The Phoenix definition of biochemical failure was used (PSA nadir+2). Treatment failure was defined as: biochemical failure or positive biopsy. RESULTS: A total of 140 patients with a mean (SD) age 69.1 yr (6.6) were included. Mean (SD) follow-up was 6.4 yr (1.1). Control prostate biopsies were negative in 86.4% of patients. Median PSA nadir of 0.16 ng/ml (range, 0.0-9.1) was achieved at a mean (SD) of 4.9 mo (5.2). A PSA nadir < or = 0.5 ng/ml was recorded in 68.4% of patients. The actuarial biochemical failure-free survival rates (SR) at 5 and 7 yr were 77% and 69%, respectively. The actuarial disease-free SR at 5 and 7 yr were 66% and 59%, respectively. CONCLUSIONS: This study demonstrates the effective long-term cancer control achieved with HIFU in patients with low- or intermediate-risk localised prostate cancer.     

Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer

BACKGROUND AND PURPOSE: Criteria for determining the durability of the response to transrectal high-intensity focused ultrasound (HIFU) ablation of prostate cancer have been established by calculating progression-free probability. PATIENTS AND METHODS: A series of 82 patients (mean age 71 +/- 5.7 years) with biopsy-proven localized (stage T1-T2) cancer who were not suitable candidates for radical surgery underwent transfectal HIFU ablation with the Ablatherm machine. The mean follow-up was 17.6 months (range 3-68 months). The mean serum prostate specific antigen (PSA) value and mean prostate volume were 8.11 +/- 4.64 ng/mL and 34.9 +/- 17.4 cm3, respectively. Progression was rigidly defined as any positive biopsy result, regardless of PSA concentration, or three successive PSA increases for patients with a negative biopsy (PSA velocity > or = 0.75). Times to specific events (positive biopsy and PSA elevation) were analyzed with the Kaplan-Meier survival method. RESULTS: Overall, 62% of the patients exhibited no evidence of disease progression 60 months after transrectal HIFU ablation. In particular, the disease-free rate was 68% for the moderate-risk group of 50 patients (PSA < 15.0 ng/mL, Gleason sum < 8, prostate volume < 40 cm3, and number of positive biopsies < 5). For the low-risk group of 32 patients (PSA < 10 ng/mL and Gleason sum < 7), the disease-free survival rate was 83%. CONCLUSION: Transrectal HIFU prostate ablation is an effective therapeutic alternative for patients with localized prostatic adenocarcinoma.     

High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology

We discuss the efficacy and safety of high-intensity focused ultrasound (HIFU) in patients with prostate cancer, to define the best indications for HIFU in daily clinical practice as primary therapy. We searched Medline and Embase for clinical studies evaluating the efficacy and safety of HIFU in prostate cancer (July 2007), and abstracts presented at the 2005-2007 annual meetings of the European Association of Urology and American Urological Association were screened. In all, 37 articles/abstracts were selected. As the data on HIFU as salvage therapy were limited, we focused on HIFU as primary therapy. Studies consisted of case series only. Included patients were approximately 70 years old with T1-T2 N0M0 disease, Gleason Score or=70 years) with T1-T2 N0M0 disease, a Gleason score of <7, a PSA level of <15 ng/mL and a prostate volume of <40 mL. In these patients HIFU achieves short-term cancer control, as shown by a high percentage of negative biopsies and significantly reduced PSA levels. The median-term survival data also seem promising, but long-term follow-up studies are needed to further evaluate cancer-specific and overall survival rates before the indications for primary therapy can be expanded.     

Control of prostate cancer by transrectal HIFU in 227 patients

PURPOSE: To evaluate the results of high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer with reference to disease-related prognostic factors. MATERIALS AND METHODS: Patients with T1-2 localized prostate cancers, prostate specific antigen (PSA) 1 ng/ml with three consecutive rises. RESULTS: The study included 227 patients. Mean follow-up was 27+/-20 months (12-121 months). Eighty-six percent had negative control biopsies. Median nadir PSA was 0.10 ng/ml. The actuarial 5-year disease-free survival rate (DFSR), combining pathologic and biochemical outcomes, was 66%. DFSR showed a significant decrease when stratified according to initial PSA level: 90% with PSA 相似文献   

Conformal proton therapy for early-stage prostate cancer

OBJECTIVES: To assess the effect of proton radiation on clinical and biochemical outcomes for early prostate cancer. METHODS: Three hundred nineteen patients with T1-T2b prostate cancer and initial prostate-specific antigen (PSA) levels 15.0 ng/mL or less received conformal radiation doses of 74 to 75 cobalt gray equivalent with protons alone or combined with photons. No patient had pre- or post-treatment hormonal therapy until disease progression was documented. Patients were evaluated for biochemical disease-free survival, PSA nadir, and toxicity; the mean and median follow-up period was 43 months. RESULTS: Overall 5-year clinical and biochemical disease-free survival rates were 97% and 88%, respectively. Initial PSA level, stage, and post-treatment PSA nadir were independent prognostic variables for biochemical disease-free survival: a PSA nadir 0.5 ng/mL or less was associated with a 5-year biochemical disease-free survival rate of 98%, versus 88% and 42% for nadirs 0.51 to 1.0 and greater than 1.0 ng/mL, respectively. No severe treatment-related morbidity was seen. CONCLUSIONS: It appears that patients treated with conformal protons have 5-year biochemical disease-free survival rates comparable to those who undergo radical prostatectomy, and display no significant toxicity. A Phase III randomized dose-escalation trial is underway to define the optimum radiation dose for early-stage prostate cancer.     

Transrectal high-intensity focused ultrasound for treatment for patients with biochemical failure after radical prostatectomy

Four patients with biochemical prostate-specific antigen (PSA) failure with suspected local recurrence at the vesico-urethral anastomotic site after radical prostatectomy were treated using a high-intensity focused ultrasound (HIFU) device (Sonablate 500) under caudal or spinal anesthesia. The pretreatment PSA levels ranged from 0.318 to 0.898 ng/mL and their Gleason scores ranged between 5 and 7. HIFU treatment was carried out six times in four patients. The median time of operation and follow-up period were 30 min (range, 15-37) and 13 months (range, 7-18), respectively. In all patients, the median PSA levels decreased from 0.555 ng/mL (range, 0.318-0.898) to 0.137 ng/mL (range, 0.102-0.290). The median PSA nadir after each HIFU was 0.054 ng/mL (range, 0.008-0.097). No major complications were noted. HIFU may be useful for the therapy of vesicourethral anastomostic lesion in patients with PSA failure after prostatectomy.     

Transrectal high‐intensity focused ultrasound for treatment of localized prostate cancer

Objectives: To assess the long‐term outcomes of transrectal high‐intensity focused ultrasound (HIFU) for patients with localized prostate cancer. Methods: From May 2003 to present, 137 consecutive patients with T1‐2 prostate cancer were treated using the Sonablate 500 and then followed for more than 12 months after their last HIFU treatment. A prostate biopsy was routinely carried out at 6 months and serum prostate‐specific antigen (PSA) was measured every 3 months after HIFU. Oncological outcomes as well as treatment‐related complications were assessed. Disease‐free survival (DFS) was judged using the Phoenix definition (PSA nadir + 2 ng/mL), negative histological findings and no local or distant metastasis. Results: The median follow up after HIFU was 36 months (range 12–84 months). No patients received adjuvant therapy during this period. The PSA nadir occurred at 2 months after HIFU and the median level was 0.07 ng/mL (0.01–2.01 ng/mL). Of the 133 patients who underwent prostate biopsy or transurethral resection of the prostate at 6 months or later after HIFU, six were positive for cancer cells (4.5%). There were no major postoperative complications, but urge incontinence (16 cases) and dysuria (33 cases) occurred after removal of the urethral catheter. The 5‐year DFS rate was 78% based on these criteria, and 91%, 81% and 62% in the low‐, intermediate‐ and high‐risk group, respectively. Conclusions: HIFU represents an effective, repeatable and minimally invasive treatment. It is particularly effective for low‐ and intermediate‐risk patients, and it should be considered as an option for localized prostate cancer.     

PSA nadir is a significant predictor of treatment failure after high-intensity focussed ultrasound (HIFU) treatment of localised prostate cancer

OBJECTIVES: To assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. METHODS: One hundred three patients after HIFU treatment (Ablatherm, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA >or=2 ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, 1 ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. RESULTS: The median follow-up was 4.9 (3-8.6) yr. Mean time to PSA nadir was 6.4+/-5.1 mo. A PSA nadir of 1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). CONCLUSIONS: The PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of 相似文献   

经直肠高强度聚焦超声系统治疗前列腺癌57例疗效分析

目的:探讨经直肠高强度聚焦超声系统(HIFU)治疗PCa的疗效。方法:使用Sonablate500型经直肠HIFU治疗系统,对57例PCa患者进行HIFU治疗,其中局限性PCa27例,晚期PCa30例。在确定生化复发之前,对局限性PCa仅行经直肠HIFU治疗;对于晚期PCa,在行经直肠HIFU治疗的同时,联合应用内分泌治疗。结果:HIFU治疗平均手术操作时间为111(86～153)min,平均术后住院时间为3.2(2～18)d。平均随访时间18(6～30)个月。局限性PCaHIFU治疗后,生化检查阴性率(PSA(4.0μg/L)在治疗后的1、2、3年分别为86%、81%和79%。30例晚期PCa治疗平均8个月(3～24个月)后,26例血清PSA<4.0μg/L(其中20例血清PSA<0.5μg/L)、21例患者前列腺体积缩小>50%。治疗后6个月时与治疗前相比,前列腺体积缩小、PSA水平降低、Qmax增加及IPSS改善差异均有显著性(P<0.05)。HIFU治疗后无严重尿道直肠瘘、尿失禁等并发症发生。结论:经直肠HIFU治疗PCa,安全、有效,并发症少,近期疗效较好,是一种可选择的PCa微创治疗方法。     

Single-session primary high-intensity focused ultrasonography treatment for localized prostate cancer: biochemical outcomes using third generation-based technology

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The experience with HIFU as a minimally invasive treatment for localized prostate cancer is relatively new and most reports are from European centres. Our study is unique in five regards: 1. Data was collected prospectively. 2. All patients were treated with contemporary technology. 3. Outcomes are reported after a single HIFU session using two definitions of biochemical failure that have the ability to predict longer‐term clinical failure after primary ablative therapies for prostate cancer (Stuttgart definition for HIFU and Horwitz definition for radiation). 4. All patients were treated in a single centre. 5. No patients underwent peri‐HIFU TURP. The present study represents the largest North American prospective cohort of primary HIFU for prostate cancer with mid‐term oncological outcome data.

OBJECTIVE

• ? To assess 4‐year biochemical failure (BCF) rates in patients after high‐intensity focused ultrasonography (HIFU) treatment using the Horwitz and Stuttgart definitions.

PATIENTS AND METHODS

• ? A total of 447 consecutive patients were treated with a single session of HIFU between May 2005 and December 2010.
• ? Follow‐up included prostate‐specific antigen (PSA) measurement every 3 months during the first year and every 6 months thereafter.
• ? Patients who had previously received radiation, androgen deprivation or HIFU therapy, and patients with <2 consecutive PSA measurements were excluded.
• ? BCF was reported using the Stuttgart (PSA nadir + 1.2 ng/mL rising) and the Horwitz (two consecutive increases of at least 0.5 ng/mL) definitions.

RESULTS

• ? In all, 402 patients met the inclusion criteria and the median (range) follow‐up was 24 (6–48) months.
• ? Of these patients, 183 (45.5%) had low and 219 (54.5%) had intermediate D'Amico's risk stratification disease.
• ? Mean and median absolute PSA nadir levels were 0.36 ± 0.69 and 0.1 ng/mL (Q₁:0, Q₃:0.37), respectively and these were achieved in median time of 3 months.
• ? Overall 4‐year mean (range) BCF‐free rates were 68 (61–75)% and 72 (68–77)% according to the Stuttgart and Horwitz definitions at 4 years, respectively.
• ? Mean (range) BCF‐free rates were significantly higher for a PSA nadir ≤0.5 ng/mL and prostate volume ≤30 mL for both definitions at 4‐year follow‐up [Stuttgart: 79 (72–86)% vs. 25 (13–38)%; Horwitz: 82 (77–87)% vs. 33 (21–44)%] and [Stuttgart: 72 (64–79)% vs. 56 (42–69)%; Horwitz: 75 (69–80)% vs. 63 (53–74)%], respectively.
• ? Pre‐treatment PSA and PSA nadir of >0.5 ng/mL were the predictors of BCF using both definitions.

CONCLUSIONS

• ? Primary HIFU appears to result in promising 4‐year BCF‐free rates in individuals with low‐ and intermediate‐risk prostate cancer who achieve PSA nadir <0.5 ng/mL.
• ? A prostate volume <30 mL is associated with PSA nadir levels of <0.5 ng/mL suggesting a potential role for pretreatment volume reduction (medically or surgically) in larger prostates.

     

Short-term outcome after high-intensity focused ultrasound in the treatment of patients with high-risk prostate cancer

OBJECTIVE: To assess the short-term outcome in patients with high-risk prostate cancer treated by transrectal high-intensity focused ultrasound (HIFU). PATIENTS AND METHODS: From April 2003 to November 2004, 30 patients with high-risk prostate cancer were enrolled in this prospective study; all had transurethral resection of the prostate before transrectal HIFU treatment, using the Ablatherm device (EDAP, Lyon, France) during the same session, associated with hormonal therapy with luteinizing hormone-releasing hormone analogues. After the procedure, all the patients were evaluated every 3 months by physical examination, prostate-specific antigen (PSA) assay and a continence questionnaire. The follow-up schedule also included a transperineal prostate biopsy 6 months after the treatment. All the patients had a minimum follow-up of 12 months. RESULTS: The HIFU treatment took a median (interquartile range, IQR) of 140 (100-160) min. No complications were reported during treatment. The mean (IQR) hospitalization was 2.2 (1-4) days, and the suprapubic drainage tube was removed after 12 (7-18) days. The complications after treatment were: urinary tract infections in five patients (16%), stenosis of the intraprostatic and membranous urethra in three (10%), and secondary infravesical obstruction in four (13%). At 12 months after the procedure, 28 patients (93%) were continent. Seven of the 30 men (23%) had a positive prostate biopsy. At the 1-year follow-up only three of the 30 patients with high-risk prostate cancer had a PSA level of >0.3 ng/mL. CONCLUSIONS: HIFU is a modern, minimally invasive therapy for prostate cancer, often used in selected patients with localized disease. The present results show that HIFU was also feasible in patients with high-risk prostate cancer. The low complication rates and favourable functional outcome support the planning of further larger studies in such patients. The oncological efficacy of HIFU should be assessed in further studies with a longer follow-up.     

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.     

Six years' experience with high-intensity focused ultrasonography for prostate cancer: oncological outcomes using the new 'Stuttgart' definition for biochemical failure

Study Type – Therapy (outcomes research) Level of Evidence 2b

OBJECTIVE

? To determine oncological outcomes after high‐intensity focused ultrasonography (HIFU) treatment in patients with localized prostate cancer using a new, more accurate, definition (‘Stuttgart’ definition) of biochemical failure.

PATIENTS AND METHODS

? We performed a retrospective review of all patients in our centre who received first‐line treatment with a second‐generation Ablatherm^TM device (EDAP‐TMS, Lyon, France). ? Oncological failure was given either by biochemical failure (prostate‐specific antigen, PSA, nadir plus 1.2 g/mL) (Stuttgart definition) or the start of salvage therapy because of a persistently positive biopsy after the HIFU procedure. ? The 5‐year biochemical‐free survival rate and 5‐year disease‐free survival rate were calculated.

RESULTS

? In total, 53 patients were included (mean age, 72.5 ± 4.5 years, range 60–79 years; 28 low risk and 25 intermediate risk). None had undergone previous hormonal therapy. Mean ±sd follow‐up was 45.4 ± 15.5 months (range 16–71 years). Mean (range) pre‐treatment PSA was 8.5 ± 4 (0.29–18) ng/mL. The median (range) PSA nadir value was 1 (0.01–14) ng/mL and occurred after a mean (range) of 5.09 (3–24) months. ? Overall, 36 patients (67.9%) experienced oncological failure. ? These included 33 cases (62.2%) of biochemical failure. A PSA nadir of ≤0.2, 0.21–1.0 and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively. ? The 5‐year biochemical‐free survival rate and disease‐free survival rate were 21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL was significantly associated with a risk of biochemical and oncological failure (P= 0.002 and P < 0.001). ? Oncological failure was not associated with any risk group. ? No patient died from prostate cancer.

CONCLUSIONS

? In our experience, Ablatherm^TM treatment for clinically localized prostate cancer was associated with a high rate of biochemical failure as determined by the ‘Stuttgart’ definition, and did not achieve effective cancer control. ? The PSA nadir value after HIFU treatment was a significant predictor of treatment failure.     

To what extent does the prostate‐specific antigen nadir predict subsequent treatment failure after transrectal high‐intensity focused ultrasound therapy for presumed localized adenocarcinoma of the prostate?

OBJECTIVE: To explore the association between the prostate-specific antigen (PSA) nadir after transrectal high-intensity focused ultrasound (HIFU) therapy for organ-confined prostate cancer and subsequent treatment failure, as defined by the presence of residual disease at biopsy 6 months after treatment. PATIENTS AND METHODS: Between January 1999 and January 2005, 115 patients in a Japanese hospital were treated using a transrectal HIFU system (Sonablate, Focus Surgery, IN, USA) for presumed localized adenocarcinoma of the prostate. All treatments were primary and none of the patients had received hormone therapy. The PSA level was measured at 2-monthly intervals and all patients had a transrectal prostate biopsy taken at 6 months. Multiple logistic regression was used to examine the relationship between PSA nadir and treatment failure, as defined by the presence of disease at biopsy. RESULTS: The PSA nadir was strongly associated with treatment failure (P < 0.001). Patients with a PSA nadir of 0.0-0.2 ng/mL had a treatment failure rate of only 11% (four of 36), compared to 46% (17 of 37) in patients with a PSA nadir of 0.21-1.00 ng/mL and 48% (20 of 42) with a PSA nadir of >1.0 ng/mL. In addition, the PSA nadir was strongly associated with both preoperative PSA level and residual prostate volume. CONCLUSION: There is a clear and intuitive association between the PSA nadir and the risk of treatment failure after HIFU. These data can be used to predict the risk of residual disease in patients with prostate cancer undergoing HIFU therapy. They can also be used to inform where the target PSA nadir should be set for this novel therapy.     

Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: Eight-year experience

Objective:   To report on the long-term results of high-intensity focused ultrasound in the treatment of localized prostate cancer.
Methods:   A total of 517 men with stage T1c–T3N0M0 prostate cancer treated with Sonablate devices (Focus Surgery, Indianapolis, IN, USA) between January 1999 and December 2007 were included in the study. Biochemical failure was defined according to the Phoenix definition (prostate-specific antigen nadir + 2 ng/mL).
Results:   The median follow-up period for all patients was 24.0 months (range, 2 to 88). The biochemical disease-free rate (BDFR) in all patients at 5 years was 72%. The BDFR in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%, 72%, 24% and 33%, respectively ( P  < 0.0001). BDFR in patients in the low, intermediate and high-risk groups at 5 years were 84%, 64% and 45%, respectively ( P  < 0.0001). The BDFR in patients treated with or without neoadjuvant hormonal therapy at 7 years were 73% and 53% ( P  < 0.0001), respectively. In multivariate analysis, pretreatment prostate-specific antigen levels (hazard ratio 1.060; P  < 0.0001; 95% confidence interval 1.040–1.080), neoadjuvant hormonal therapy (hazard ratio 2.252; P  < 0.0001; 95% confidence interval 1.530–3.315) and stage ( P  = 0.0189) were demonstrated to be statistically significant variables. Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients who were preoperatively potent.
Conclusions:   High-intensity focused ultrasound therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer, particularly those with low- and intermediate-risk cancer.     

The feasibility and safety of high-intensity focused ultrasound as salvage therapy for recurrent prostate cancer following external beam radiotherapy

OBJECTIVES

To investigate the use of minimally invasive high‐intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT).

PATIENTS AND METHODS

A review of 31 cases treated using the Sonablate® 500 HIFU device, between 1 February 2005 and 15 May 2007, was carried out. All men had presumed organ‐confined, histologically confirmed recurrent prostate adenocarcinoma following EBRT.

RESULTS

The mean (range) age was 65 (57–80) years with a mean preoperative PSA level of 7.73 (0.20–20) ng/mL. The patients were followed for a mean (range) of 7.4 (3–24) months. Side‐effects included stricture or intervention for necrotic tissue in 11 of the 31 patients (36%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in two (7%). Recto‐urethral fistula occurred in two men, although one was due to patient movement due to inadequate anaesthesia, so the ‘true’ rate is 3%. Half of the patients had PSA levels of <0.2 ng/mL at the last follow‐up. Three patients had metastatic disease whilst another two had only local, histologically confirmed, failure. A further four patients had evidence of biochemical failure only. Overall, 71% had no evidence of disease following salvage HIFU.

CONCLUSIONS

Salvage HIFU is a minimally invasive daycase procedure that can achieve low PSA nadirs and good cancer control in the short term, with comparable morbidity to other forms of salvage treatment. The issue of accurate staging at the time of recurrence is still problematic, as a proportion of these men will harbour microscopic metastases undetected by conventional staging investigations.     

High‐intensity focused ultrasound for localized prostate cancer: initial experience with a 2‐year follow‐up

OBJECTIVE

To report on the short‐term functional and oncological results, from one institution, of high‐intensity focused ultrasound (HIFU) for treating localized prostate cancer.

PATIENTS AND METHODS

Over a 3‐year period, 43 patients with localized prostate cancer were scheduled for HIFU in the primary (31) and salvage (12) settings using a second‐generation Ablatherm^TM device (EDAP, Lyon, France). Oncological failure was defined by several criteria, including biochemical failure (assessed using both the Phoenix definition of the nadir + 2 ng/mL) and the current Food and Drug Administration (FDA) trial endpoint of a prostate‐specific antigen (PSA) level of ≥0.5 ng/mL, or starting salvage therapy, or the presence of cancer on biopsy after treatment.

RESULTS

Three patients had their procedures abandoned due to technical limitations/rectal wall thickness. The mean PSA levels in the primary and salvage groups were 9.2 and 5.1 ng/mL, respectively. The mean HIFU treatment time in the primary and salvage groups was 71.1 and 63.3 min, respectively. Using the Phoenix definition of biochemical failure, HIFU treatment failed in 13 patients in the primary group (46%) and five in the salvage group. Using the FDA trial endpoint, HIFU failed in 21 patients in the primary group (75%) and eight in the salvage group. One man died from metastatic prostate cancer 18 months after salvage HIFU. There were two urethral strictures in the primary (7%) and one in the salvage treatment group. There were two prostato‐rectal fistulae in the salvage HIFU group.

CONCLUSIONS

HIFU is proposed to be a minimally invasive low‐morbidity ablative treatment for localized prostate cancer, and with good efficacy. The present limited series is unable to support these claims. There were significant rates of complications and oncological failure in both the primary and salvage setting. As a result we have suspended our programme pending further evidence of its safety and efficacy.     

Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 Patients

Background

High-intensity focused ultrasound (HIFU) is an emerging treatment for select patients with localized prostate cancer (PCa).

Objectives

To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter database.

Design, setting, and participants

Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study. Previously irradiated patients were excluded from this analysis. In case of any residual or recurrent PCa, patients were systematically offered a second session. Kaplan-Meier analysis was performed to determine disease-free survival rates (DFSR).

Measurements

Prostate-specific antigen (PSA), clinical stage, and pathologic results were measured pre- and post-HIFU.

Results and limitations

A total of 803 patients from six urologic departments met the inclusion criteria. Stratification according to d’Amico's risk group was low, intermediate, and high in 40.2%, 46.3%, and 13.5% of patients, respectively. Mean follow-up was 42 ± 33 mo. Mean PSA nadir was 1.0 ± 2.8 ng/ml with 54.3% reaching a nadir of ≤0.3 ng/ml. Control biopsies were negative in 85% of cases. The overall and cancer-specific survival rates at 8 yr were 89% and 99%, respectively. The metastasis-free survival rate at 8 yr was 97%. Initial PSA value and Gleason score value significantly influence the DFSR. The 5- and 7-yr biochemical-free survival rates (Phoenix criteria) were 83–75%, 72–63%, and 68–62% (p = 0.03) and the additional treatment-free survival rates were 84–79%, 68–61%, and 52–54% (p < 0.001) for low-, intermediate-, and high-risk patients, respectively. PSA nadir was a major predictive factor for HIFU success: negative biopsies, stable PSA, and no additional therapy.

Conclusions

Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy (EBRT). The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT.