The clinical applications of high intensity focused ultrasound in the prostate

Abstract

Purpose: To review the current status of high intensity focused ultrasound (HIFU) therapy in the prostate, in particular the treatment of prostate cancer.

Materials and methods: Two trans-rectal devices are currently in clinical use; the SonablateR500 and AblathermR. These devices are compared and similarities and differences highlighted.

Results: Outcomes from the primary treatment of prostate cancer, and HIFU as a salvage therapy are discussed. The rate of adverse events are described after each of these, and the role and safety of other therapies after primary HIFU failure are outlined. Factors which may influence outcome such as use of neo-adjuvant androgen suppression are discussed.

Conclusions: Trans-rectal HIFU for prostate cancer is a promising technique with medium-term oncological results broadly comparable to standard therapies. It is the only form of therapy which is non-invasive and does not utilise ionising radiation. This is an exiciting field undergoing rapid developments, both in the technology and the way in which prostate cancer as a disease is managed.

• HIFU
• prostate
• ablation
• focused ultrasound
• cancer

Introduction

Prostate cancer is the most common cancer in men and the second leading cause of death from malignancy [1], [2]. The mainstays of treatment are still radical surgery or radiation therapy; however, there are several minimally invasive treatments now under evaluation which may prove to be of equivalent oncological effectiveness in the long-term [3].

The most common radical therapy–surgical excision of the prostate–has been shown to have a modest impact on disease-specific survival in men with cancer confined to the prostate [4]. Over a 10-year period surgery offered a 5% increase in survival over observation alone (decreasing the disease-specific mortality from 14% to 9%). The side effects of the most common radical treatments (surgery and external beam radiotherapy–EBRT) are high–they include amongst others deterioration in urinary, sexual and bowel functio [5], [6]. The profile and probability of these harmful outcomes depend to a large extent on the type of radical treatment, but all occur as a consequence of damaging tissue or structures that exist outside the prostate gland–the external sphincter, the neurovascular bundles and the rectal mucosa, respectively. Refinements in the traditional radical therapies (conformal or intensity modulated radiation therapy on the one hand vs. laparoscopic or robotic radical prostatectomy on the other) have had little impact on the key treatment related morbidities [7], [8].

The desirable attributes for a new technology in this field have been outlined previously [9] (see box 1). What is required is a truly conformal, non-invasive means of performing radical treatment for prostate cancer; reducing the side effect profile while maintaining oncological efficacy. Trans-rectal high intensity focused ultrasound (HIFU) has the potential to do this [10]. Hight intensity focused ultrasound has been used on an experimental and clinical basis as non-invasive therapy for clinically localised prostate cancer since the 1990s [10]. It has also been used experimentally for the treatment of benign prostatic conditions, but has fallen out of favour on the basis of poor long-term clinical outcome data [11].

Box 1 Desireable attributes of a new tissue ablation technology for prostate cancer (from Gillett et al. [9]).

• Administered with the patient under local anaesthesia

• Real time monitoring of treatment

• Excellent oncological efficacy (destruction of all prostate cancer)

• Minimal inflammatory response

• No adverse effect on pre-treatment erectile function

• No adverse effect on pre-treatment urinary continence

• No injury to adjacent structures (rectum, bladder)

• Repeatable

• Low cost

• Outpatient treatment

Devices in widespread clinical use

There are currently two trans-rectal HIFU devices licensed in Europe for the treatment of prostate cancer, the Ablatherm® (EDAP-TMS, Lyon, France) and the Sonablate®500 (Focus Surgery, Indianapolis, IN, USA), see Figures 1 and 2, respectivley. These devices have both similarities and differences which are outlined in Table I. The Ablatherm® has been used for the longest period of time for the treatment of prostate cancer, having now been used to treat over 10 000 patients worldwide (GR, ter Haar, Personal Communication, 2006). These treatments have predominantly been in Europe, and as a result of the more widespread use of this device, it has the longest follow-up data associated with it. The Sonablate has been used most in the Far East, and is now becoming more common in Europe (particularly the UK); the total number of patients treated with this device is now approaching over 1000 (P. Mikus, Personal Communication, 2006). Both systems may be used as a primary therapy or to treat recurrent disease following external beam radiation, brachytherapy or previous HIFU.

Figure 1. The Ablatherm® therapy platform demonstrating the probe integrated into treatment bed (console not shown) (Courtesy of EDAP-TMS).

Figure 2. The Sonablate®500 mobile console, articulated Probe Arm, Probe, and Sonachill™ cooling unit (Courtesy of Focus Surgery, Inc.).

Table I.  Similarities and differences between the Sonablate®500 and Ablatherm® systems.

	Differences
Similarities	Sonablate®	Ablatherm®
Units consist of user interface, ultrasound generator, imaging system, chiller and trans-rectal probe	User may vary input power manually depending upon the visual changes seen during treatment	Pre-defined power levels depending upon primary, salvage or repeat HIFU treatments
Trans-rectal probe enclosed in a sheath	Lithotomy treatment position on standard operating table	Right lateral decubitus treatment position on integrated table
May be administered under spinal/epidural or general anaesthetic	Recommended use without prior procedure to the prostate	Recommended use immediately following ‘mini’ trans-urethral resection of the prostate/Bladder neck Incision
Real time prostate imaging	Multiple transducers of different focal lengths housed within single probe tip. Each transducer driven at 4 MHz and used for planning and therapy	Single, multifrequency probe tip. 7.5 MHz transducer for planning set confocally within a 3 MHz treatment transducer
User input to delineate the prostate boundaries	Smaller volume treated in each acoustic exposure, necessitating treatment in three ‘blocks’ being planned–anterior, middle and posterior	Larger volume treated in each acoustic exposure, antero-posterior dimension of the prostate covered in single exposure
Fluid circulated around probe tip to cool both rectal wall and transducer
Mechanism of prostate ablation both thermal and mechanical
Procedure time around 3 hours in total
Real-time rectal wall distance monitoring
CE approved in Europe
FDA trials underway in the USA

Defining outcome

A problem facing all new technologies used to treat organ-confined prostate cancer is the length of time required to generate outcome data. True figures regarding the disease-specific mortality following radical prostatectomy have only recently become available. These show only a modest improvement in survival at 10 years after treatment vs. watchful waiting [4] in men with well to moderately differentiated prostate cancer. Because of this, proxy measures of outcome must be used, with biopsy negativity and ASTRO (American Society for Therapeutic Radiology and Oncology) criteria [12] the most common. A recent article has shown that a low prostate specific antigen (PSA) nadir following treatment is strongly correlated with good outcome on subsequent post-treatment biopsy [13], and evidence of persistent enhancement on post-treatment contrast-enhanced magnetic resonance (CI-MR) imaging also strongly predicts both failure on biopsy and subsequent PSA nadir as criteria [14].

Primary treatment

The largest case series of patients treated with the SB-500 comes from Dr Uchida's group in Japan. They report the results from a cohort of 63 patients with localised prostate cancer who had not undergone prior hormone manipulation. Patients had a mean baseline PSA of 11.2 ng/ml, and a mean Gleason score of 6. The mean follow-up period was 23.3 months, ranging from 3 months to 63 months. They achieved a negative biopsy rate of 87% 6 months after treatment [15], with a PSA nadir of <1 ng/ml in 72% of patients treated. At a mean of 5-Years follow-up [16] they showed a freedom from biochemical recurrence (FBR) (based on ASTRO criteria) of 78% – in particular, patients with a pre-treatment PSA of 10 ng/ml or less showed 94 and 77% biochemical disease free survival at 4 and 5 years follow-up, respectively (181 patients). It is important to note that this group used pre-determined power levels defined from in vitro and in vivo experimentation [16] rather than visual feedback to influence power levels administered during HIFU in their series.

‘Visually directed’ HIFU is a novel technique in which real-time, hyper-echoic changes seen on B-mode ultrasound imaging during treatment are used to influence the input power given by the user [17]. The operator aims to generate grey scale changes throughout the target tissue; during treatment power levels (energy exposure) are under constant adjustment by the operator in order to achieve discrete or confluent grey-scale changes within the defined treatment zone (termed Uchida Grade I or Grade II, respectively). By obtaining these changes the operator is able to control energy in the target zone that is either on or just below the visual cavitation threshold. This grey scale feedback is also used to provide a ceiling threshold. Uchida Grade III changes occur when uncontrolled hyper-echoic changes occur in the near field. This undesirable deposition of energy is corrected by reducing energy exposure. Visually directed HIFU therefore takes into account both inter- and intra-prostatic differences in acoustic and thermal properties, and allows the user to respond in real time to the therapy.

It has been suggested that lower PSA nadirs may be achieved using direct visual feedback to tailor treatment to the individual. In a small cohort of patients with organ confined prostate cancer who had not undergone prior androgen deprivation a PSA nadir of ≤0.2 ng/ml in 84% of patients treated, and an unrecordable PSA in over 30% was achieved using this method of visual direction. Visually directed HIFU, while being a logical approach to treatment and certainly giving the operator a sense of control over the treatment process, has not yet been shown to improve outcome in the medium term over algorithm based treatments which are arguably more reproducible. Time will show whether this technique is both reproducible between centres and translates to improved biopsy negativity and freedom from disease in the longer-term.

Blana et al. [18] reported results from a study of 146 patients with localised prostate cancer using the Ablatherm® device. Patients had a baseline PSA ≤15 ng/ml, and a Gleason score ≤7. The mean follow-up period was 22.5 months, ranging from 4 months to 62 months. After HIFU treatment, 93.4% of the patients had negative control biopsies. The median (rather than the mean) PSA nadir was 0.07 ng/ml, and the PSA level was maintained at 0.15 ng/ml after a mean follow-up of 22 months. A confounding influence in this study was the use of neo-adjuvant androgen suppression (AS) in 63 patients (43%). This may have had an influence on the PSA nadirs achieved after treatment by influencing the PSA kinetics. Thuroff et al. [19] reported the 5-year results from the European multicentre trial of the Ablatherm®, treating 402 patients at six centres presenting with localised disease. Of the 288 patients who were analysable, the negative biopsy rate at 6 months after treatment was 87.2%, after a mean 1.4 treatment sessions. The re-treatment rate of 27.9% was not interpretable however, as the treatment protocol changed during the study from two, partial gland ablations to a single, whole gland ablation.

These series compare very favourably to a recent study by Potters et al. [20] that compared 7-year outcome data between cohorts undergoing radical prostatectomy (RP) (746 patients), external beam radiotherapy (EBRT) to a minimum 70Gy (340 patients) and low dose rate seed brachytherapy (LDR BT) (733 patients). The oncological outcome was defined as FBR based on ASTRO criteria for EBRT and LDR-BT, and PSA <0.2 for RP. FBR was similar in all three groups; 74, 77 and 79% at 7 years for LDR-BT, EBRT and RP, respectively.

Adverse events after primary HIFU therapy

The adverse event rates for this procedure have been described for both clinical devices. Having treated 181 patients, Uchida et al. (using the Sonablate®) found a pre-sphincteric stricture rate of 22%, epidiymitis occurring in 6%, a rectourethral fistula in 0.5%, erectile dysfunction in previously potent men 20% and no stress incontinence lasting more than 1 month. In the cases of pre-sphincteric strictures all were managed with periodic urethral dilatation. The experience of UK clinicians using ‘visually directed’ HIFU is similar–at a recent meeting of European users of the SB-500, a cohort of 81 patients treated in London was described in which the stricture rate was 15%, infection rate 6% and erectile dysfunction in previously potent men of 25%. In this group grade 1 stress incontinence persisted more than 3 months in 4% of those treated [21].

Blana et al. [18] describe the complications experienced treating 223 patients using the Ablatherm®. They report an infection rate of 0.4%, grade I stress incontinence in 7.2% and an infravesical obstruction rate of 19.7%. The decision to perform TURP routinely before Ablatherm® HIFU was partly as a result of a feasibility study by Vallancien et al. [22] on 30 patients, which showed improved urinary function with no associated increased morbidity with a combined procedure. Also, in a cohort study of 271 patients treated for localised prostate cancer by Chaussy and Thuroff; 96 received HIFU alone and 175 combined therapy under a single anaesthetic [23]. There was no influence on biopsy negativity or PSA nadir, however in the combined group the time to catheter removal was significantly reduced (from 40 to 7 days).

Overall these figures are very acceptable compared to other radical therapies such as radical prostatectomy, which even in the hands of high volume surgeons may have a long-term incontinence rate in the primary treatment setting (requiring surgical intervention) of almost 7% [24].

Salvage HIFU following failure of external beam radiotherapy

Approximately one third of patients with localised prostate cancer are treated with radical EBRT. Recurrence rates have been shown to be between 30% and 40% [25] in these patients and for those with localised radio-recurrent prostate cancer, limited curative treatment options are available [26]. Salvage prostatectomy is a technically difficult procedure with unsatisfactory cure rates and very high complication rates, far exceeding those from primary surgery [27]. Salvage surgery is normally only considered in patients with a >10-year life expectancy and is often not an attractive option for these patients who are likely to have been deemed unsuitable for, or declined radical surgery as their first line treatment prior to radical radiotherapy. Salvage cryotherapy is an alternative minimally invasive technique that appears to be a valid option [28], however there is limited data available at present. Salvage brachytherapy has also been used as a potentially curative option, in a cohort of 49 patients, Grado et al. [29] achieved a biochemical disease-free survival rate of 34% at 5 years, however further experience with this technique will need to be gained before it can be used more widely.

Salvage HIFU using both the Ablatherm® and Sonablate® devices have been reported following recurrence of prostate cancer after initial EBRT. Gelet et al. [30] reported on 71 patients treated with the Ablatherm® who had biopsy-proven recurrence and no evidence of metastasis on bone scan, abdominal computer tomography +/− pelvic magnetic resonance imaging. A third of these had also received neo-adjuvant androgen suppression. Mean follow-up was 14.9 months (range 6 to 86 months). Following treatment, 80% of patients had negative control biopsies, however 40 patients (56%) required adjuvant therapy during the follow-up period due to either residual tumour (19.7%) or a rising PSA from another site of metastasis (36.6%). Four men died due to metastatic disease. This reflects the high-risk nature of patients undergoing treatment for recurrent disease, and the high likelihood of extra-prostatic spread in the face of a complete local ablation.

More recently, Murat et al. [31] reported a follow-up of the group described earlier by Gelet. This cohort now stood at 118 patients, with the mean interval from EBRT to HIFU 4.1 years, and the mean follow-up after salvage HIFU 16.4 months. Negative follow-up biopsies were obtained in 84%, and overall 52% of patients required no salvage hormone deprivation as they were free from disease on the basis of biopsy and stable PSA. The actuarial progression free survival rate was dependent on initial risk (D’Amico Risk Classification [32]) and was 78% for low-risk patients, 49.5% for intermediate-risk patients and 14% for high risk patients.

A small cohort of patients treated with salvage Sonablate® HIFU after radiation therapy failure has been presented [33]. Eighteen patients with biopsy proven, locally recurrent disease were treated in two centres. All had a single session of HIFU under general anaesthetic and were treated using the ‘visually directed’ technique [17]. Of the 18 patients, 14 had received prior androgen deprivation, however all had detectable PSAs. At the time of presentation 11 had more than 3 months follow-up, and six of these had a PSA nadir of <0.2 ng/ml. Of the four who had not achieved a low or stable nadir, two subsequently were confirmed to have metastatic disease.

The difficulties in treating EBRT failures include the both the interpretation of the biopsies after radiotherapy and ensuring that patients have no extra-prostatic spread. It is likely, that in those patients with high-risk disease, some may have micro-metastases not detected by standard radiological investigations at the time of their salvage HIFU. De Jong et al. [34] showed that the site of recurrence was correctly identified in 78% of patients who had a biochemical relapse after EBRT using choline-labelled positron emission tomography (PET) and this may offer a useful tool in the selection of patients with high-risk disease. There is no clear consensus as to when biopsies should be performed after suspected radical radiotherapy failure as biopsy samples in the months following radiotherapy should be interpreted with caution. When considering offering salvage HIFU experts suggest [35] that a positive biopsy should be considered to be pathological when associated with evidence of biochemical failure.

Adverse events after salvage HIFU therapy

The complication rates for salvage HIFU are higher than those for primary HIFU, as would be expected. Using the Ablatherm® device, the rectal fistula rate was initially 6% overall [30]. These parameters (used form primary therapy) were subsequently modified in order to account for the reduced vascularity and the fibrosis that occurs in irradiated tissue, and using these there have been no further fistulae reported in the last 65 patients treated [35]. Murat et al. [31] reported an incontinence rate of 43%, with 23% experiencing severe (grade II or III) incontinence and 20% mild stress incontinence (grade I). The incidence of these other complications has also significantly reduced with the modified treatment parameters, the incidence of grade III incontinence has fallen from 16% to 5% and pre-spincteric stenosis reduced from 35% to 6% since 2002. The effect of salvage HIFU on erectile function is yet to be reported but is currently under evaluation.

Of the small cohort treated with the Sonablate® device, 17 patients are evaluable for adverse event reporting [33]. Illing and Emberton describe three urinary tract infections, one pre-sphincteric stricture and one grade I incontinence persisting beyond 3 months of treatment.

Treatment options following failed primary HIFU therapy

Trans-rectal HIFU is considered by some to have an ‘expected’ re-treatment rate. Most of the larger cohort studies using either Ablatherm® or Sonablate® cite the ‘average’ number of HIFU sessions to be between 1.2 and 1. [36], [37]. Blana et al. [38] reviewed the complications following primary or repeat Ablatherm® HIFU and found a statistically significant increase in the cumulative incontinence and impotence rates. The rate of impotence increased from 26.5% before HIFU, to 65.3% after one session and 81.6% after two sessions; the rate of stress incontinence increased from 4.1% before treatment, to 8.2% after one session and 16.3% after two HIFU sessions. Although this analysis has not been performed on the Sonablate® treated patients it is probable that a similar pattern would be found.

Salvage radical prostatectomy has been performed, although largely in the setting of Phase I/ II trials during the development of prostate HIFU to ensure the completeness of ablation [39]. Most clinical series of patients undergoing HIFU do not wish to have, or are unable to undergo surgery at the time of primary diagnosis, and are therefore unlikely to receive surgery in the setting of primary treatment failure. Beelage et al. [40] describe 14 patients who underwent partial prostatic ablation prior to surgical resection; they reported no problems during the operation nor any change to the postoperative course compared to patients not treated with HIFU. Not only were the treatments partial, these patients also underwent resection 12 days after HIFU therapy, thus not giving the gland time to slough or fibrose. To the authors knowledge there have been no formal series of salvage radical prostatectomy with intent to cure following failed primary HIFU reported.

Pasticier et al. have presented the results from a cohort of patients undergoing salvage radiotherapy due to persistent localised disease after treatment with HIFU [41]. Forty-five patients were treated with external beam radiotherapy (EBRT) alone or EBRT with combined hormonal deprivation. They received an average of 71Gy radiation dose and at a mean follow-up of 26 months, incontinence rates were not significantly increased 1 year post-EBRT compared to the rates prior to EBRT. At 5 years the actuarial survival free of salvage androgen deprivation was 42% and overall there did not appear to be a significant increase in morbidity associated with salvage EBRT after HIFU. This suggests that EBRT is a feasible and safe salvage treatment for patients choosing HIFU as their primary treatment for prostate cancer.

The effect of androgen suppression

A major confounding factor in many of the reported case series for both the Sonablate® and Ablatherm® is the use of hormone therapy. It is customary to undertake HIFU in men with presumed localised prostate cancer without the use of AS. However there are times when AS is used. Most commonly it is used to shrink the gland in order to make treatment possible. It has been used in this way by radiation oncologists for many years [42]. Another reason for the use of AS relates to its use to reduce the risk of progression to a minimum when a prolonged interval is anticipated between staging and treatment. The last, and most contentious may be related to a belief that there may be a synergistic effect between AS and HIFU. This is analogous to the belief that AS prior to and during radiotherapy to the prostate results in a sensitisation of the cells to this form of therapy. If this assertion were true for HIFU as opposed to radiation therapies, the hypothesis would be that the hormonally cytoreduced prostate would be in some way more susceptible to ischemic and or thermal injury. Uchida et al. [43] explored the effect of neo-adjuvant AS on cancer-related outcomes following HIFU. They compared a cohort of 154 men who had received AS with 96 who had not; the primary outcome measure being treatment failure as defined by the presence of prostate cancer at a control biopsy 6 months after treatment. There was no statistically significant difference in biopsy negativity between the groups. This is reassuring for those men who undergo AS as primary therapy and for whatever reason seek to change treatment. It also means that neo-adjuvant cytoreduction can be used to render large glands treatable without obviously prejudicing the outcome. A reasonable conclusion from this analysis relates to restricting the use of AS before HIFU. AS therapy is not without harm to the patient [44] and also disrupts PSA kinetics; if a large benefit is unlikely to be associated with its use, then it should probably be restricted to specific roles, i.e. size reduction and temporising.

Discussion

The trend in all surgical disciplines is for less invasive treatments. Open surgery has given way to laparoscopic procedures in many areas, and needle-ablative therapies (such as cryotherapy and radiofrequency ablation) are gaining ground [45], [46]. The next conceptual change is the ability to treat entirely non-invasively–and in HIFU this is realised.

High intensity focused ultrasound has many of the desirable attributes of a new ablative technology (Box 1). It may be administered under local/regional anaesthesia, however the trend, certainly in the UK, is to use general anaesthesia. Real time monitoring of the treatment may be performed using either the Ablatherm®, or Sonablate® and in the latter, the information gained from the monitoring may be used by the clinician to guide therapy in a ‘visually directed’ manner. So far the oncological data looks promising–although long-term results are not available, 5-year data is now emerging which appears comparable to all of the current mainstream modalities for the treatment of organ confined prostate cancer. The side effect profile, too, appears very promising–reported incontinence, erectile dysfunction and infection rates all appear better than current modalities. The urethral stricture rate is high and currently under evaluatio [21], [38]. Further attractions of HIFU are that it is repeatable, of relatively low running cost and does not provide a therapeutic impasse–surgery and radiotherapy, as well as further HIFU sessions, are possible following initial treatment failure [16]. It is important to acknowledge however, that patient selection bias and different reporting criteria complicate any comparison between series, either when considering different devices or modalities. A limitation when considering the efficacy and side effect profile of trans-rectal HIFU, as of many new techniques, is that randomised control trials are difficult to perform [47].

There is a great deal of research work underway in the field of focused ultrasound, both clinically and in the laboratory. In 2006, investigation into aspects of HIFU have generated over one million pounds in UK Government research grants from the Engineering and Physical Sciences Research Council (EPSRC) alone [48]. Considerable work has already taken place into the development of phased array transducer technology [49]. Most clinical devices in use have either single element therapeutic transducers or multi-element arrays which act as a single element. Transducers with annular arrays, allowing the focal point to be electronically moved towards and away from the transducer face and 2D arrays which allow horizontal, lateral and vertical translation of the focal point without moving the transducer itself, have already been constructed for experimental purposes. Coupled with this, speckle tracking technology is in development which may allow software to follow the movement of a target over time–such as through the respiratory cycle, or if the target organ changes shape during the procedure due to oedema [50]. This paves the way for a system which not only does not have to physically move during the treatment, but also may account for any intra-operative changes automatically.

Visual changes are not the only method of real-time feedback. Tissue elastography [51] and ultrasound thermometry [52] are in development but remain experimental; magnetic resonance imaging [53] may accurately detect temperature changes however MR devices are costly, do not provide feedback as instantaneously as B-mode ultrasound and have not been used clinically in the setting of trans-rectal prostate HIFU.

Novel methods enhancing the effect of focused ultrasound are in development. Injected microbubbles have not only been used as a contrast agent, but also to enhance ablation [54] and also to aid the delivery of genes and chemotherapy [55]. Added to this are the potential synergistic effects of combining focused ultrasound with ionising radiation, which have yet to be explored, but which may have a role in the treatment of high-risk or locally advanced disease.

Work is also being carried out to develop a transurethral (rather than trans-rectal) high intensity ultrasound device using planar (rather than focused) ultrasound. This may enable a significant reduction in treatment time, as defocusing the beam allows a greater volume of ablation during a single exposure [56]. The potential difficulty of this method is ensuring the completeness of ablation at the periphery of the gland, where the tumours are most likely to be.

Lastly, interest is growing in the effect of ablative technologies on immune up-regulation [57], potentially provoking the body into producing an innate anti-tumour response following treatment.

Over the next decade the field of prostate cancer therapy may alter radically. Not only will new drugs and devices emerge (possibly based on those areas outlined) but there may also be a paradigm shift in the way that early disease is viewed. Whatever the modality, the current treatment for organ confined disease is ‘radical’ – the whole gland is treated, as well as the prostate cancer within it. The reasons for this are straightforward; prostate cancer may be multi-focal in nature, detection of small foci of disease has been difficult and the tools to perform such precise treatment were missing. Already this picture has changed–a range of new modalities for targeted treatment have emerged, of which HIFU is arguably the most promising [58], and improvements in imaging and biopsy technique allow greater levels of confidence that all significant foci of disease have been accounted for [59]. There is no doubt that prostate cancer can be multi-focal, but if the targeting and treatment methods are sufficiently accurate there is the potential for a ‘male lumpectomy’, much in the same way as radical mastectomy has been superseded by lumpectomy for early stage breast cancer in women [60]. This has the potential to greatly reduce the associated side effects of radical treatment for prostate cancer, and indeed trials are currently underway to assess the feasibility of this approach.

Conclusions

Trans-rectal HIFU, using either of the devices currently available, is the only non-invasive ‘radical’ therapy for prostate cancer which does not involve ionising radiation. Medium term oncological outcome data look similar to results from standard therapies, and it is hoped that treatment tailored to the individual may improve results further. The published side effect profile following trans-rectal HIFU is also better than current standard therapies.

There is a great deal of interest in this field, and developments are underway to refine both the conduct of therapy and the devices in use. There is potentially a paradigm shift in the way early stage prostate cancer is treated–more accurate diagnosis coupled with the accuracy of HIFU could pave the way to widespread use of focal therapy for early stage disease.