Approximately a third of patients diagnosed with localized prostate cancer undergo external-beam radiotherapy (EBRT) as a primary curative treatment option [1]. Unfortunately, 5-year biochemical failure rates following EBRT are as high as 50% and these result in the majority of prostate cancer-specific deaths [2–4]. Prostate-specific antigen (PSA) testing allows the early detection of recurrent or residual tumor, following EBRT, and the identification of patients who require further treatment either with hormone manipulation (with the intention of disease control) or definitive salvage therapy (with the intention of cure) [5]. The mainstay of the latter has been salvage radical prostatectomy, with large series reporting 43% 10-year progression-free survival rates [6]. However, radiation effects make this a technically challenging procedure with extremely high complication rates that exceed primary surgery [6]. Furthermore, many patients who undergo EBRT as a primary treatment do so as they are unwilling or unsuitable for surgery in the first instance and, therefore, are not suitable for salvage operation.

Cryoablation and interstitial brachytherapy have been investigated as minimally invasive salvage treatment alternatives with varying results and definitions of success [7–9]. More recently, high-intensity focused ultrasound (HIFU) has been applied to the treatment of prostate cancer [10,11]. The aim of this minimally invasive technology is to deliver lethal doses of heat to the prostate in a targeted manner, thus ablating cancer cells and sparing the periprostatic tissues that are essential for maintaining function and quality of life [12]. A transrectal probe focuses ultrasound energy across intact mucosa to a focal point within the target tissue; from this focus, a defined ellipsoid ‘lesion’ propagates out, causing coagulative necrosis and ultimate ablation of the tumor cells within. A succession of adjacent lesions is created in order to treat the gland in its entirety. Attractions of HIFU for localized prostate cancer treatment include a short hospitalization time, minimal invasiveness, a biochemical response within 3 months and the ability to repeat the treatment if indicated. Prior transurethral surgery is not a contraindication and has actually become a routine part of the procedure in some centers [13]. Nevertheless, patients must be able to tolerate an anesthetic (either general or spinal) and a period of postoperative catheterization. Although yet to gain US FDA approval in the USA, equipment is becoming widely available in Asia, Europe and Canada with a short operator learning curve of ten cases for those already experienced in transrectal ultrasound [11]. Recent 5-year results of HIFU as a primary treatment have demonstrated 78% biochemical disease-free survival [10].

Gelet’s group in Lyon, France, has the most extensive experience with HIFU as a salvage therapy for radiotherapy failures [14]. They report a series of 71 men with biochemical and biopsy-proven EBRT failure, and established negative nodal and metastatic status, who underwent salvage HIFU treatments. Two thirds of these had presalvage moderately or poorly differentiated disease. Patients were assessed with 3-monthly PSA tests and control biopsies at 3 months, with further biopsies in the event of a rising PSA; the mean follow-up was 15 months (range: 6–86 months). Overall, 80% of patients had negative biopsies (73% actuarial at 30 months) and a median PSA nadir of 0.2 was achieved. The predicted 30-month actuarial disease-free rate, defined as negative biopsies and absence of biochemical failure, was 38%. Complications included four cases of rectourethral fistulae, 12 bladder neck stenosis treated with urethrotomy and 25 cases of incontinence, four of which were treated with artificial sphincters. During the observed period, further safety parameters were introduced to the treatment protocol and the authors assert that no fistulae have occurred since [15].

The data have recently been updated and reported on 118 men with a mean follow-up of 16.4 months [15]. Survival rates without the requirement for salvage androgen deprivation correlated with the initial pre-HIFU gleason score groups of 6 or less, 7 and 8 or more, and were 58, 44 and 14%, respectively [15].

The data concerning HIFU for the treatment of localized prostate cancer, whether as a primary or salvage treatment are, to date, too immature to allow an accurate assessment of efficacy in terms of definitive cure. However, initial results suggest that HIFU offers a minimally invasive salvage treatment option for patients who are either unsuitable for, or unwilling to undergo, surgery. The developments of treatment protocols and safety features have led to reduced side effects, making HIFU an attractive proposition for the significant proportion of men who desire cure following radiotherapy failure without surgery.