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

The literature concerning the efficacy and safety of transrectal high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer still comprises a relatively small number of articles. The main studies have been published by four teams using an apparatus available in Europe for several years. The recently presented results of the European Multicentre Study and the study by Gelet and associates based on 242 patients with a follow-up of more than 1 year show that HIFU is a valid alternative for the management of welldifferentiated and moderately differentiated localized prostate cancer with an initial PSA 10 years. In two studies, the combination of transurethral resection of the prostate and HIFU limited the risk of postoperative urinary retention without inducing a higher complication rate. In a series of patients presenting recurrence after external-beam radiotherapy, HIFU was found to be a useful therapy, with >80% negative biopsies. The best indications for HIFU are men over the age of 65, those who are not candidates for radical prostatectomy, obese patients, or patients with comorbidities likely to make surgery more difficult. The learning curve for this technique is relatively short, between 10 and 15 patients, for urologists experienced in transrectal ultrasonography. One of the advantages of HIFU is that it can be repeated in the case of recurrence or to re-treat a prostatic site, it involves no radiation, and patients do not suffer from long-term irritative urinary symptoms.     

Principles and results of high-intensity focused ultrasound for localized prostate cancer

Focused ultrasound holds promise in a large number of therapeutic applications. It has long been known that high-intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible, with the development of high-power ultrasound arrays and noninvasive monitoring methods. In the last decade, HIFU have been adapted and used to treat localized prostate cancer and it is now commercially available in Europe. In this article, preclinical studies and clinical development of prostate HIFU as well as early clinical results from our center and international studies are reviewed. Early results demonstrated that prostate HIFU is efficient to obtain local control for low- and intermediate-risk localized prostate cancer; however, long-term follow-up is still needed to estimate the efficacy of prostate HIFU in terms of specific cancer mortality. This makes HIFU a viable alternative in patients not candidate for radical therapy.     

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.     

Morbidity associated with repeated transrectal high-intensity focused ultrasound treatment of localized prostate cancer

The aim of this cross-sectional study was to compare single with repeated high-intensity focused ultrasound (HIFU) treatment in patients with localized prostate cancer, regarding treatment-related morbidity. A number of 223 consecutive patients with localized prostate cancer were treated with HIFU. Among them, 174 (78%) patients had one treatment, while 49 (22%) needed a second treatment. The patients’ status and treatment-related side effects were followed up. The complications rates after one HIFU in 223 patients were: urinary tract infection 0.4%, chronic pelvic pain 0.9%, infravesical obstruction 19.7%, stressincontinence 7.6%, impotence 49.8%. Among the 49 patients who received a second HIFU therapy, the cumulative incontinence rate (12.2%; P = 0.024) and cumulative impotence rate (55%; P < 0.001) were significantly increased. Although there is an increase in morbidity if transrectal HIFU is repeated, the risk of side effects related to additional HIFU sessions in the case of primary treatment failure is still low.     

High-intensive focused ultrasound in localized prostate cancer

BACKGROUND AND PURPOSE: The results of the standard treatment for prostate cancer-radical prostatectomy-are not entirely satisfactory. A new local therapy, transrectal high-intensive focused ultrasound (HIFU), has been developed. We reviewed our experience with HIFU for palliation of localized prostate cancer. PATIENTS AND METHODS: Our series included 65 men with confirmed prostate cancer without detectable metastases who were not suitable candidates for radical prostatectomy. After prophylactic suprapubic cystostomy, the patients were treated using the Ablatherm version 2.32 under spinal anesthesia. The effects were monitored by serum prostate specific antigen assays, digital rectal examination, and biopsy. The mean follow-up is 10 months (range 1-18 months). RESULTS: There were no intraoperative or postoperative deaths, and there have been no deaths from prostate cancer. Residual cancer was detected in 35% of the patients in whom only biopsy-positive portions of the prostate were treated and 17% of those in whom the entire gland was treated. Retreatment was performed 1 month after the first session in these patients. The prostate volume increased an average of 30% after treatment, but by 3 months, the gland was 10% to 20% smaller than its original size. Three patients suffered complications secondary to overheating of the rectal wall or treatment too close to the external urethral sphincter. CONCLUSION: The low morbidity, minimal invasiveness, avoidance of systemic side effects, and potentially curative effect make HIFU a potentially useful option for the treatment of localized prostate cancer.     

Location of residual cancer after transrectal high-intensity focused ultrasound ablation for clinically localized prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? Transrectal High‐Intensity Focused Ultrasound (HIFU) ablation has been used as a minimally invasive treatment for localized prostate cancer for 15 years. Five‐year disease‐free survival rates of 66–78% have been reported, challenging the results of external‐beam radiation therapy. Usually, a 6‐mm safety margin is used in the apex to preserve the urinary sphincter and potency. The influence of this 6‐mm margin on the results of the treatment has never been assessed. This retrospective study of a cohort of 99 patients who underwent systematic biopsy 3–6 months after HIFU ablation for prostate cancer (with a 6‐mm safety margin in the apex) shows that post‐HIFU residual cancer is found more frequently in the apex. Therefore, new strategies improving the prostate destruction at the apex while preserving the urinary continence need to be found.

OBJECTIVE

? To evaluate whether the location (apex/midgland/base) of prostate cancer influences the risk of incomplete transrectal high‐intensity focused ultrasonography (HIFU) ablation.

PATIENTS AND METHODS

? We retrospectively studied 99 patients who underwent prostate cancer HIFU ablation (Ablatherm; EDAP, Vaulx‐en‐Velin, France) with a 6‐mm safety margin at the apex, and had systematic biopsies 3–6 months after treatment. ? Locations of positive pre‐ and post‐HIFU sextants were compared. ? The present study included two analyses. First, sextants negative before and positive after treatment were recoded as positive/positive, hypothesizing that cancer had been missed at pretreatment biopsy. Second, patients with such sextants were excluded.

RESULTS

? Pre‐HIFU biopsies found cancer in all patients and in 215/594 sextants (36.2%); 55 (25.6%) positive sextants were in the apex, 86 (40%) in the midgland and 74 (34.4%) in the base. ? After treatment, residual cancer was found in 36 patients (36.4%) and 50 sextants (8.4%); 30 (60%) positive sextants were in the apex, 12 (24%) in the midgland and eight (16%) in the base. ? Both statistical analyses found that the locations of the positive sextants before and after HIFU ablation were significantly different (P < 0.001), with a higher proportion of positive apical sextants after treatment. ? At the first analysis, the mean (95% confidence interval) probability for a sextant to remain positive after HIFU ablation was 8.8% (3.5–20.3%) in the base, 12.7% (5.8–25.9%) in the midgland and 41.7% (27.2–57.89%) in the apex. ? At the second analysis, these same probabilities were 5.9% (1.9–17%), 9.9% (3.9–23.2%) and 27.3% (13.7–47%), respectively.

CONCLUSION

? When a 6‐mm apical safety margin is used, residual cancer after HIFU ablation is found significantly more frequently in the apex.     

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.     

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.     

超声造影评价高强度聚焦超声治疗局限性前列腺癌早期疗效的临床研究

目的 探讨超声造影对高强度聚焦超声（HIFU）治疗局限性前列腺癌早期疗效评价的应用价值.方法 采用HIFU-2001型高强度聚焦超声肿瘤治疗系统,对17例局限性前列腺癌进行治疗.治疗前及治疗后1个月分别行超声造影检查,观察瘤体内部及周边组织血流灌注信号特点,据此判定疗效.同时根据直肠指检、经直肠前列腺B超检查前列腺肿块大小、血清PSA等结果进行客观疗效判定.将两疗效判定结果进行对比分析.结果 HIFU治疗前,所有前列腺低回声结节均呈快速高增强.HIFU治疗后,超声造影显示治疗有效15例,其中无增强12例、少量低增强3例;无效2例,仍表现为快速高增强.客观疗效判定有效15例,血清PSA下降幅度均≥50%,其中2例前列腺结节体积缩小≥50%;无效2例,血清PSA、前列腺低回声结节大小体积均与治疗前水平相当.客观疗效判定结果与超声造影结果相符.结论 超声造影能准确显示HIFU治疗局限性前列腺癌的消融范围及程度,是评价早期治疗效果的可靠方法.     

Salvage radiotherapy after high-intensity focused ultrasound treatment for localized prostate cancer: feasibility, tolerance and efficacy

Background:

The objective of this study is to evaluate the feasibility, tolerance and efficacy of salvage external beam radiotherapy (EBRT) in persistent or recurrent prostate cancer after failed high intensity focused ultrasound (HIFU) therapy.

Methods:

We reviewed data on tolerance and oncologic outcomes for all patients with biopsy-proven locally recurrent or persistent prostate cancer who underwent salvage EBRT in our department between April 2004 and June 2008. Minimum follow-up for inclusion was 2 years. Failure with EBRT was defined as biochemical relapse (Phoenix definition) or introduction of androgen deprivation therapy (ADT). Gastrointestinal and urinary toxicity and urinary stress incontinence were scored at 12 and 24 months (Radiation Therapy Oncology Group and Ingelman Sundberg rating, respectively).

Results:

The mean age of the patients was 68.8 years (range: 60–79). Mean prostate-specific antigen (PSA) before EBRT was 5.57 ng/mL (range: 2.5–14.8). Median follow-up was 36.5 ± 10.9 months (range: 24–54). No patient received adjunctive ADT. The EBRT course was well-tolerated and completed by all patients. The mean PSA nadir was 0.62 ng/mL (range: 0.03–2.4) and occurred after a median of 22 months (range: 12–36). One patient experienced biochemical failure and was prescribed ADT 30 months after EBRT. The disease-free survival rate was 83.3% at 36.5 months. There was no major EBRT-related toxicity at 12 or 24 months.

Conclusions:

Our early clinical results confirm the feasibility and good tolerance of salvage radiotherapy after HIFU failure. Oncological outcomes were promising. A prospective study with longer follow-up is needed to identify factors predictive of success for salvage EBRT therapy after HIFU failure.     

High-intensity focused ultrasound therapy for clinically localized prostate cancer

The efficacy of high-intensity focused ultrasound (HIFU) used for the treatment of localized prostate cancers has been demonstrated over the past decade. We present our early results after HIFU used as a single session in patients with clinically localized prostate cancer. A total of 58 patients were treated using the Ablatherm HIFU device with or without transurethral resection of the prostate (TURP). HIFU failure was defined as the presence of a cancer remnant on repeated biopsies or three consecutive increases in the prostate-specific antigen (PSA) >/=1.0 ng/ml. The mean follow-up was 14 months (range, 6-21 months). After HIFU treatment, 78% of patients had a decreased PSA level to <0.5 ng/ml within 3 months. The median value of the last PSA was 0.6 ng/ml and the median nadir PSA was 0.2 ng/ml. The success rates of HIFU were 85, 77 and 47% in low-, intermediate- and high-risk groups, respectively. The HIFU failure rate was closely associated with clinical stage, presence of cancer on TURP chips and nadir PSA on univariate analysis. However, the only significant predictor for HIFU failure was the nadir PSA value by multivariate Cox regression analysis. The operation-related complications were minimal. Although both the period and number of patients were limited to evaluate the clinical efficacy, HIFU appears to be a safe and effective treatment option in selected patients with prostate cancer.     

Energy-based ablative therapy of prostate cancer: high-intensity focused ultrasound and cryoablation

PURPOSE OF REVIEW: This review is an update on the role of the two minimally invasive techniques in primary therapy of organ-confined prostate cancer: as a salvage option after standard-therapy failure and for focal ablation of index tumors. RECENT FINDINGS: Energy-based ablative techniques are of growing interest for today's heterogeneous spectrum of prostate cancer. At present, primary high-intensity focused ultrasound appears to be a valid alternative to active surveillance protocols in low-risk cancers and, in older patients, to standard therapy. Morbidity is low, although postoperative impotence occurs frequently. Cryoablation has higher morbidity, even with third-generation conformal technology. With radiorecurrent cancer the potential radiation damage of the rectal wall renders transrectal high-intensity focused ultrasound more hazardous. Third-generation cryoablation seems to give better cancer control with lower morbidity in this situation. Unfortunately, long-term outcome data from controlled trials are not available. SUMMARY: These minimally invasive techniques are not magic bullets, and patients must be informed accordingly. Focal ablation of the prostate segment with the index cancer would minimize morbidity and therefore appears highly appealing. Its success depends on correct localization of the lesion. Until this is achieved with sufficient reliability by appropriate biopsy or imaging techniques it remains strictly experimental.     

经直肠高强度聚焦超声联合内分泌疗法治疗前列腺癌

目的探讨经直肠高强度聚焦超声联合内分泌疗法与单纯内分泌疗法治疗前列腺癌的疗效。方法将40例前列腺癌患者分为A、B两组，其中A组采用HIFU联合内分泌治疗，B组采用单纯内分泌治疗。HIFU治疗采用Sonablate 500型经直肠HIFU治疗系统，内分泌治疗采用去势加用抗雄激素药物治疗。随访时间8—24个月，平均16个月。结果A、B两组患者在治疗后，均出现了前列腺体积缩小，血清PSA均有不同程度下降，IPSS评分降低，Qmax明显提高，治疗前后差异有统计学意义（P〈0．05）。其中A组较B组改变更为明显，两者之间差异有统计学意义（P〈0．05）。结论高强度聚焦超声联合内分泌疗法及单纯内分泌疗法对前列腺癌的近期疗效均较好，前者疗效更为明显。     

Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, 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 pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.