Ultrasound Treatment for Prostate Cancer: Finding the Middle Ground
Ultrasound Treatment for Prostate Cancer: Finding the Middle Ground
Abstract & Commentary
By William B. Ershler, MD
Synopsis: The experience of two referral centers in London, UK, on the short-term outcomes of high-intensity-focused ultrasound (HIFU) for prostate cancer ablation, revealed the approach to be effective in short-term control but not without toxicity. The latter included the occurrence of either urethral stricture or retained necrotic material in the prostate, requiring intervention in almost one-third of patients. Although long-term results are needed, HIFU appears to be an alternative to radical prostatectomy, radiation therapy, or active surveillance, with intermediate efficacy and safety outcomes.
Source: Ahmed HU, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: The first UK series. Br J Cancer. 2009;101:18-26.
Primary treatment for prostate cancer includes either radical surgical resection or radiation therapy, both of which have proved effective in achieving long-term survival, but at the risk of significant morbidity including incontinence and impotence.1,2 In contrast, surveillance alone has spared, or delayed, these adverse consequences for some, but at the risk of allowing progressive tumor growth and spread that might reduce the chance for long-term survival for others.3 Furthermore, the psychological burden of non-treatment may be unacceptable for some prostate cancer patients. Thus, there remains a perceived need for an intermediate form of therapy and, in this regard, high-intensity-focused ultrasound has been promoted as one of several minimally invasive "ablative" techniques, with emerging evidence regarding both safety and efficacy. Other techniques in the same category include cryosurgery, radiofrequency ablation, and photo-dynamic therapy.
HIFU relies on the physical properties of ultrasound, which allow it to be brought into a tight focus either using an acoustic lens, bowl-shaped transducer, or electronic-phased array. When the energy density at the focus is sufficiently high, tissue damage occurs through coagulative necrosis. The treatment planning, execution, and monitoring are controlled using an interface that allows the surgeon to target the area of treatment, adjust the focal length of the transducer, and alter the power delivered to each focal zone.4
In the current report, Ahmed et al present their experience with HIFU treatment for primary breast cancer. They performed an analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between February 1, 2005 and May 15, 2007, who presented at either of two referral centers.
A total of 172 men were treated under general anesthetic as day-case procedures, with 78% discharged a mean five hours after treatment. At the time of the analysis, the mean follow-up was 346 days (range 135-759 days). Either a transurethral or suprapubic catheter was required for a mean of 13.9 days (± 8.3 days), and 30.2% required intervention for either a stricture or retained necrotic material within the prostate. Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs. 40.4%, p < 0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection, and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172), with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae.
Regarding toxicity, two questionnaires were employed: the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-15 (IIEF-15). The IPSS score significantly deteriorated at three and six months but returned to baseline at nine and 12 months after treatment. Of those that completed the IEFF-15 questionnaire (n = 94), there was also a significant drop in score at three months compared with baseline but no significant difference at other times compared with baseline.
In all, 78.3% achieved a PSA nadir < 0.5 mg/ml at 12 months, with 57.8% achieving < 0.2 mg/mL. Of the 172 patients, there was no evidence for active disease (defined as a PSA < 0.5 ng/mL or negative biopsy in 159 (92.4%). Of the 13 with persistent disease, eight were retreated with HIFU, one had salvage external beam radiotherapy, and four chose active surveillance.
Commentary
Thus, HIFU is an ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Nonetheless, proponents of the approach should reconsider the notion of touting it as "minimally invasive," at least in the context of toxicity. Nearly one-third of patients required intervention because of stricture or retained necrotic material and the three- and six-month evaluations revealed significant drops in IPSS scores. In this regard, HIFU clearly provides "middle-ground" between the more aggressive surgical or radiation approaches and that of watchful waiting (active surveillance).
This was a short-term analysis and, clearly, the impressive cancer control outcomes need to be examined over a longer period. Experience from other trials, albeit utilizing other approaches, would suggest that a nadir of < 0.5 ng/mL may not be sufficiently stringent to predict long-term survival.5 Thus, Ahmed et al's conclusions, consistent with those of the National Institute of Clinical Excellence (UK),6 are that this procedure be offered to selected patients on a contingency that outcome data are assimilated onto one of the several national or international registries designed to demonstrate the long-term consequences of this approach. It's hard to argue with this conclusion. Certainly, if these preliminary findings, or those from other "ablative" approaches, are confirmed in long-term analysis, clinicians and patients will have the benefit of an alternative, intermediate approach to localized prostate cancer.
References
1. Bill-Axelson A, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005;352:1977-1984.
2. Holmberg L, et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002;347:781-789.
3. Carter HB, et al. Expectant management of prostate cancer with curative intent: an update of the Johns Hopkins experience. J Urol. 2007;178:2359-2364.
4. Illing RO, et al. Visually directed high-intensity focused ultrasound for organ-confined prostate cancer: A proposed standard for the conduct of therapy. BJU Int. 2006;98:1187-1192.
5. Ganzer R, et al. PSA nadir is a significant predictor of treatment failure after high-intensity focused ultrasound (HIFU) treatment of localised prostate cancer. Eur Urol. 2008;53:547-553.
6. Graham J, et al. Diagnosis and treatment of prostate cancer: summary of NICE guidance. BMJ. 2008;336: 610-612.
The experience of two referral centers in London, UK, on the short-term outcomes of high-intensity-focused ultrasound (HIFU) for prostate cancer ablation, revealed the approach to be effective in short-term control but not without toxicity.Subscribe Now for Access
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