Open access peer-reviewed chapter - ONLINE FIRST

High Intensity Focused Ultrasound (HIFU) in Prostate Diseases (Benign Prostatic Hyperplasia (BPH) and Prostate Cancer)

Written By

Carlos M. Garcia-Gutierrez, Habid Becerra-Herrejon, Carlos A. Garcia-Becerra and Natalia Garcia-Becerra

Submitted: December 28th, 2021 Reviewed: January 13th, 2022 Published: March 8th, 2022

DOI: 10.5772/intechopen.102663

Advances in Soft Tissue Tumors Edited by Hilal Arnouk

From the Edited Volume

Advances in Soft Tissue Tumors [Working Title]

Dr. Hilal Arnouk

Chapter metrics overview

36 Chapter Downloads

View Full Metrics


The minimally invasive, image-guided therapies are a clear option in the urologists’ armamentarium to treat BPH and prostate cancer. During the last decade, advances in the HIFU systems improved the capacities to scan, fuse MR images to target a specific zone, situation that improved the safety and possibility to ablate the cancer in a focalized location or a whole gland ablation, preserving continence and erections, with a proper selection of patients, with good results, comparable with surgery or radiation. In some post radiation failures, it is a very safe option to treat the recurrent cancer. In the case of BPH, the flexibility to ablate exclusively the prostate enlargement, preserving the urethra is a great advantage, considering a fast procedure, no bleeding, and a highly precise treatment, with improvement in the voiding function, improving IPSS and uroflowmetry parameters.


  • BPH
  • HIFU
  • prostate cancer
  • focal therapy
  • partial gland ablation
  • hemiablation
  • lower urinary tract symptoms
  • LUTS
  • transurethral resection of prostate
  • prostate-specific antigen

1. Introduction

Clinical benign prostate hyperplasia is an aging disease, with a high prevalence after 40 years of age, from 8 to 60% at 90 years. The interventional treatments include open adenoma removal, transurethral resection of the prostate, HOLMIUM, and THULIUMenucleation, laser vaporization, steam ablation, microwavethermotherapy, etcetera. Prostate cancer has a high incidence in men over 60 years and is considered the second cause of death. Early detection assisted by PSA (prostate-specific antigen), MR imaging, and in some centers PSMA PET SCAN, and targeted biopsies, let us offer less invasive techniques, compared with radical prostatectomy or external beam radiation, with a decrease of morbidity, achieving what has been called “TRIFECTA”: disease control, urinary continence and erectile function.

High intensity focused ultrasound, a relatively new technique, uses a sound beam directed to a specific spot inside the prostate parenchyma, causing thermal ablation with customized planning, including whole gland, the benign enlargement of localized lesions, defined as focal therapies. More than 50,000 treatments have been performed worldwide, with growing improvement in the outcomes, mainly caused by a good selection of cases and technical improvements of imaging and emission of sound beams. By 2010, Sonablate and Ablatherm devices were used widely in some countries of Latin America (Mexico, Brazil, Ecuador, and Argentina), Europe and Japan, in 2015 FDA cleared the usage of HIFU with both machines. Some countries still consider HIFU as experimental therapy [1, 2].


2. Bases of HIFU

2.1 Physics of HIFU

Sound has been for several centuries a subject of interest for the different branches of science, been the development of its understanding as a physical phenomenon and its use in the different fields of science and technology the main topics. The medical sciences have not been the exception in this search. Ultrasound, a technology derived from sound, has had a significant boom in medicine due to its implementation as a diagnostic or therapeutic instrument. It has been widely disseminated as a diagnostic instrument due to its various advantages ranging from cost–benefit to high sensitivity and specificity for diagnosing pathologies [3]. As a therapeutic option, ultrasound has been used for the development of technologies such as extracorporeal lithotripsy, HIFU, sonophoresis, sonodynamic therapy, sonothrombolysis or histotripsy, among others, which base their efficacy on the induction of sonic bio-effects, both thermal and non-thermal (cavitation, radiation, etcetera) to induce tissue changes [4, 5].

The difference between ultrasound as a diagnostic or therapeutic technology is based on inducing a certain amount of bioeffect at the tissue level [4]. Ultrasound as a diagnostic tool seeks to induce the least possible bioeffect [4, 6]. In contrast, ultrasound as a therapy seeks certain technologies to achieve tissue ablation through inducing thermal or non-thermal bioeffects, such as the HIFU [4, 5, 6].

HIFU had its first antecedents in 1942 when the first destruction of tissue was recorded through an extracorporeal ultrasound energy source [5]; later, in the 1990s, its technology was refined by integrating real-time imaging methods for monitoring the procedure [5]. The use of real-time imaging has improved the efficacy of this treatment, reducing morbidity and mortality at making the treatment more accurate [5, 7]. Its clinical implementation increased significantly after the clinical case report of a patient treating a malignant bone neoplasm in Chongqing, China, in 1997 [5]. During the following 15 years, the use of HIFU clinically reported more than 30,000 cases of kidney, pancreas, bone, liver, or uterine fibroids, showing its great utility as a minimally invasive technology [5, 8]. Currently, HIFU technology can be divided according to the radiological technique used to guide the procedure (Magnetic Resonance or Diagnostic Ultrasound) or according to the system used to deliver the energetic (transrectal for the treatment of prostate pathologies, interstitial for the treatment of biliary or esophageal tumors, extracorporeal for the treatment of organs accessible to sound through the skin) [5, 7, 9].

For this chapter, and to delve into HIFU therapy and its biophysical effects, it is necessary to understand some basic concepts of the physics of sound.

Soundcan be defined as a wave, classified as a transverse or longitudinal wave [5, 7]. For the chapter, and because it is the most used form in medicine, the longitudinal wave classification will be used [7].

Once a pulse is generated, the energy will oscillate the particles closest to the origin of the pulse, and these particles will, in turn, oscillate with those immediately adjacent so that this energy will be transmitted from proximal to distal. Each pulse generates positive pressure and negative pressure in one wave, together are wave cycles [5, 7].

Frequency, the number of wave cycles (one positive part and negative part of a wave) that occur in one second is measured in Hertz (one wave cycle per second = 1 Hert) [5, 7].

Amplitudeis the distance that the most positive or negative part of each wave cycle has about the basal pressure of the medium [5, 7].

Intensity-Power; Poweris defined as the amount of ultrasound energy that a device generates; the tissue receives this energy, this is where the intensitycomes in; Intensitycan be defined as the amount of energy that passes through a point in 90°, so it is expressed as the amount of power divided by the unit of area, Watts/cm2 [5, 7].

The HIFU as a therapeutic ultrasound system generates an intensity of approximately 1000–20,000 W/cm2, generating an elevation of between 60 and 100° C in 1 second in that unit area while using a frequency around 0.8−5 MegaHertz (each MegaHertz = 106 Hertz) (Figure 1) [4, 6, 8].

Figure 1.

Sound properties. Schematic representation of sound properties. Created

2.2 Biologic effects of HIFU

Multiple bio-effects have been described (thermal and non-thermal) related to the exposure of a sound field by a tissue. Different authors have classified these as thermal and non-thermal bio-effects [4, 5]. For its part, the HIFU system predominantly generates thermal bio-effects; however, these are not pure, since the presence of other non-thermal bio-effects such as cavitation has been described in the same tissue [4].

The main bio-effect caused by HIFU has been compared to the use of a magnifying glass to focus the sun’s rays on a point [6] because it generates a frequency of 0.8−5 MegaHertz with a wavelength of 2−0.3 mm, this is translated into a small area subjected to great ultrasonic power [6, 7]. As we previously mentioned, when this power crosses a specific point can be translated into intensity, being in the case of HIFU between 1000−20,000 watts/cm2 [5, 6]. It is considered that it is necessary to raise the temperature of the tissue to 56–60° C or more for about a second to produce an irreversible cytotoxic lesion with protein denaturation and heat-induced coagulative necrosis; using this concept of the irreversible lesion induced by heat, the result can be inferred from raising the temperature to around 60–100° C at a focal point as occurs with HIFU therapy (Figure 2) [4, 5, 6].

Figure 2.

Temperature changes are produced at the focal point, and near the transducer. (Courtesy of HIFUMx).

2.2.1 Coagulative necrosis

In different in vivo studies, it has been observed that the main effect caused by HIFU as a thermal injury is the induction of coagulative necrosis through protein denaturation and induction of apoptosis via nuclear lysis by endonucleases [5]. Specific characteristics have been described that differentiate this coagulative necrosis derived from thermal injury from coagulative necrosis of ischemic origin. The difference is mainly due to the predominance in the interaction of giant cells with chronic inflammation, unlike the tissue regeneration process via granulation tissue seen in coagulative necrosis due to ischemia [5].

Associated with coagulative necrosis, the ability of HIFU to injure small-caliber vessels (<2 mm) has been described as an endothelial lesion, and thrombosis of these vessels with these characteristics has been found in various studies. However, the ability of larger vessels to dissipate temperature has been described, thus suffering minor injury (heat sink) (Figure 3) [5].

Figure 3.

Thermal ablation. Schematic representation of thermal ablation mechanism and specificity.

2.2.2 Cavitation

The second most crucial mechanism described during the HIFU treatment is the non-thermal bio-effect of a mechanical type induced through cavitation [5, 9]. Cavitation can be defined as gas or vapor cavities forming within a liquid medium and their subsequent dynamics in this medium [5]. Cavitation formation can occur under different conditions (hydrodynamic, thermal, or acoustic energy changes); its importance lies in the possibility of generating a lesion adjacent to the formation of these cavities through micro-boiling, increased temperature, and shear stress [4, 5]. Cavitation, unlike temperature-induced injury, is more unstable in nature and less predictable (Figure 4) [5].

Figure 4.

Mechanical destruction. Schematic representation of mechanical destruction mechanism and specificity.

Two types of cavitation have been described by their nature, stable (non-inertial) cavitation and transient (inertial) cavitation [4]. Transient cavitation involves a significant change in bubble size in a period of few acoustic cycles [4], resulting in a more aggressive collapse [4, 5]. In contrast, stable cavitation maintains a more stable range in terms of growth of its diameter without significant growth and remains stable during many acoustic cycles [4, 5].

The appearance of these cavities depends on the different properties of both the source of acoustic energy and the medium where this energy will be exerted. Generally, it is known that to a greater extent, the temperature and pressure exerted on the medium are essential determinants for the formation of cavities. The temperature is inversely proportional to the cavitation threshold (the possibility of a said event happening) [4, 5].

Its importance lies in the possibility of causing more significant tissue damage, currently a field of study for the development of therapies such as histotripsy, which base their efficacy on this principle (Figure 5).

Figure 5.

Massive controlled cavitation formed in the posterior aspect of the prostate adenoma (Urovallarta Urology Center).


3. HIFU systems

3.1 EDAP - Ablatherm

The first HIFU technology used for the treatment of prostate cancer to become available was Ablatherm® (Edap-Technomed, Lyon, France), with initial clinical results published in 1996 [10].

The Ablatherm system uses separate crystals to produce an image (7.5 MHz) and to deliver treatment (3 MHz), and since 2005, the two types of transducers have been integrated into the same probe, which has a focal point of 45 mm from the crystal. The 3 MHz treatment crystal creates an ablation zone with a volume that can range from 29 mm3 to 36 mm3. The Ablatherm has 3 different types of treatment algorithms, each designed for a specific application: HIFU as primary treatment, HIFU as secondary treatment after failed Radiation Therapy, and HIFU re-treatment [11].

The Ablatherm has a mechanism to detect patient movement based on an internal automatic A-mode ultrasound detection system, which together with the external ultrasound used during the treatment planning phase, measures the distance from the rectal wall, and ensures that the patient has not moved [12].

Treatment with the Ablatherm is performed with the patient in a lateral decubitus position, on their right side. This is done as a precautionary measure, since if there were any bubbles in the liquid around the transducer used for the treatment, these would rise out of the treatment field, with the patient on their side, and the bubbles would not remain between the transducer crystal and the prostate [13].

3.2 Focal one

Focal One® (Edap-Technomed, Lyon, France) is the first HIFU device, specifically designed to perform focal therapy and was introduced for the focal treatment of prostate cancer. With this device, the procedure is performed on a conventional surgical table with the patient in a lateral position to avoid air bubbles in between the crystal and the rectal wall.

The transducer that uses focal one is a dynamic focus transducer, made with 16 isocentric rings, each ring is moved by a dedicated electronic system, composed of 16 lines, this allows the user to move the focal point of the transducer to a maximum of 8 different points that are between 32 and 67 mm from the transducer. The dynamic approach treatment involves unitary HIFU lesions, stacked in the prostate, within the axis of the ultrasound. Each lesion measures approximately 5 mm and by stacking 2 to 8 lesions it is possible to extend the necrotic area by 5 to 40 mm [14].

3.3 Sonablate

Focus Surgery (Indianapolis, IN, USA) introduced the Sonablate500® system and preliminary results of its use for the treatment of prostate cancer were published in 2002 [15]. The Sonablate uses a single crystal to obtain the images and to deliver HIFU treatment, to achieve this, the Sonablate uses a transducer that has two crystals placed back-to-back.

At frequencies of 6/4 MHz, it can provide good image quality and effective treatment, respectively. The 6 MHz frequency probe provides good resolution of the anterior prostate but has a lower resolution of the posterior prostate margin and rectal wall, compared to higher frequency transducers. Originally, the operator could choose between different crystals depending on the size of the prostate, with a focal length of between 30 and 40 mm.

The Sonablate does not have a real-time imaging system while the treatment is given, but instead alternates between the treatment mode and image acquisition to create an image overlay that is used to detect patient movement; this is achieved by placing images of treatment planning along with images taken during treatment, if both images are aligned, it is indicative that there has been no movement of the patient (Figure 6) [16].

Figure 6.

Schematics of the HIFU transducer used in the Sonablate system and the focal point within the tissue.


4. Magnetic resonance guided HIFU therapies MRgFUS (Magnetic Resonance guided focused ultrasound surgery)


Insightec, a company located at Tirat Carmel, Israel, developed a system called EXABLATE 2100, which produces high-intensity focused ultrasound real-time guided by MRI. The focused ultrasound is delivered through an endorectal probe, with a 990-element phased-array transducer.

Once the probe is placed inside the rectum, it is filled with degassed water, producing an interface between the prostate and rectal wall. The MRI imaging includes T1-weighted dynamic contrast-enhanced, T2-weighted, and diffusion-weighted sequences, to accurately localize the lesion to be treated; with these images the EXABLATE software lets the user plan, manually contouring the area, including 5 mm tumor-free margins. The system then produces a specific treatment protocol, calculating the energy required and the number of shots to be delivered, avoiding damage to peripheral tissue. A pretreatment low energy targeting is delivered, checked with MRI thermometry. This information is overlapped on the anatomic images. Once confirmed, full power sonications are produced, monitorization is done with real-time MRI thermometry. A successful therapy is considered when the temperature in sonicated tissue achieves a threshold of 65°. A complete treatment is considered when non-perfused areas on MRI are found [17]. During the 2021 AUA meeting, the FDA 510 k clearance was informed.

4.2 Profound-TULSA-pro

The prostate therapy system is called TULSA, which stands for Transurethral Ultrasound Ablation. The device is designed to perform prostate tissue ablation in a transurethral approach. The probe is placed through the urethra, once in place, MRI guidance in real-time is used, so the treatment must be done in MRI suites.

In the main module, using high-definition MRI images, the prostate is contoured, during the planning step, the area to be treated is defined, preserving the urethra, and a 3 mm margin of apical prostate immediately above the sphincter [18, 19]. As described by the company [18], it is possible to treat bigger prostates compared with the ultrasound-guided devices.

The TULSA system uses a robotically-driven directional thermal ultrasound; the probe has 10 independent transducers, each of them delivering therapeutic ultrasound, so it is totally customizable, the user can select the number of elements to be used, depending on the length of the prostate. The probe includes a water pump cooling system, and an endorectal cooling device keeps 1 to 2 mm periurethral and rectal protected from thermal damage.

The therapy is done using an intraurethral rotational movement of the probe, creating a “sweeping heating pattern,” directional energy, with in-and-out sonication into the prostate parenchyma. The probe is fixed by an MRI robotic system, controlling the linear and rotational movements. The real-time MRI guidance, shows the thermal changes inside the treated volumes, every 6 seconds, allowing the users to modify the treatment parameters if needed. At the end of the ablation, a complete MRI revision is done, showing with the thermometric measures, all the missing areas that did not receive adequate energy, reassuring a safe and complete treatment [20].


5. HIFU applications

5.1 Benign prostate hyperplasia (BPH)

The use of HIFU for the treatment of BPH has been described since 1992. The physical principle for treating an adenoma is not different from whole gland treatment. Tissue temperatures in the range of 80–90° C can produce thermoablation of the treated tissue, and it is possible to induce intra-prostatic cavities comparable to post-TURP effects.

In a series of 50 cases of prostatectomies after treatment with HIFU, it was possible to study the extent of coagulative necrosis caused by HIFU. Madersbacher reports that the prostate volume that can be destroyed during BPH treatment, with a probe with a focal length of 3−5 cm, is 8 cm3, and 14 cm3 with a focal length of 4 cm, so he calculates that approximately 25−30% of the total prostate could be destroyed during the procedure in these patients while keeping the tissue damage on the adjacent tissues minimal [21].

These results encouraged the search for new, less invasive treatment techniques to alleviate lower tract symptoms while reducing possible adverse effects. The main difference in the treatment of BPH against the whole gland lies in the possibility of delimiting the treatment area only to the prostatic adenoma, leaving the rest of the prostate intact.

In order to decrease the rate of complications due to TURP, Ebert et al. reported the use of HIFU for the treatment of prostate enlargement in 50 patients using a Focus Surgery HIFU generator. The short-term results were interesting, with a mean increase in Qmax from 5.7 to 11.6 ml/s at 6 weeks post-treatment, while the incidence of complications seems to be in favor of HIFU versus TURP [22].

In another report by Madersbacher et al., where 98 patients underwent HIFU for BPH, the author obtained similar results of improvement in urodynamic parameters at 12 months post-treatment, however, in the long-term follow-up, they observed that 43.8% of the treated patients had to undergo re-treatment with TURP due to unsatisfactory clinical results [23].

Both authors concluded that this method is promising, and although the long-term results were not satisfactory, they noted that there was a lot of variability in the results due to the heterogeneity of patients with inclusion criteria (prostate size, detrusor activity, middle lobe, etc.) So more protocols are needed to identify the ideal patient for this technique.

Currently, the authors of this chapter are working on the development of a novel technique for the treatment of BPH using a Sonablate HIFU device, with an up-to-date HIFU system and improved protocols: using higher energies, looking to modify the cavitation threshold, to achieve more cavitation than thermal lesions, with promising results in the time of treatment, catheterization and reduction volume of adenoma.

5.2 Prostate cancer

5.2.1 Whole gland treatment

In the last 20 years, the indications for HIFU have expanded, from its original indication for prostate ablation in localized prostate cancer in patients who were not the candidates for radical prostatectomy to hemi ablation or focal therapy for localized disease or as salvage therapy after failed radiation therapy [24]. Patient selection

Whole gland prostate ablation with HIFU as primary treatment is indicated in patients with localized prostate cancer (T1 - T2, Nx, M0) without high-risk factors. They must not have any anorectal pathology that prevents the correct placement of the endorectal transducer.

The physician must be mindful of the anteroposterior diameter of the prostate and the focal point of the HIFU device he or she is using, since the prostatic tissue that is beyond the focal point will remain outside the ablation zone. If the dimensions of the prostate exceed the capabilities of the transducer in the longitudinal or transverse planes, it is possible to reposition the probe and perform the ablation in two or more phases, but it is not possible to reach tissue beyond the focal point.

It is also important to ensure that there are no significant prostatic calcifications, especially if they project posterior acoustic shadow, since the ultrasound beam could bounce off these calcifications, potentially compromising the oncological outcome of the procedure or the integrity of the rectal wall. It is a common practice to perform a TURP prior to HIFU treatment to remove large calcifications or reduce prostate size, and the procedure can be safely performed 6 weeks after TURP. The HIFU procedure

The HIFU procedure in the prostate is performed using a HIFU generator connected to an endorectal transducer, which contains piezoelectric crystals capable of generating ultrasound waves; this can alternate between high energy for ablation and low energy for image visualization [25].

The endorectal tube is usually connected to a cooling system that maintains the rectal wall at a temperature between 14 and 16°C. The procedure begins with the introduction of the probe and the visualization of the field to be treated. While Ablatherm requires a special surgical table, and the patient is placed in the lateral position, with Sonablate the patient is in a dorsal position and is performed on a standard surgical table.

Treatment planning is a bit different between devices, with the Ablatherm, the prostate is divided into 4 to 6 volumes, and is treated apex to base, slice by slice in an automated process. With Sonablate, the treatment is carried out in 2 to 3 coronal layers, starting with the anterior area and moving towards the posterior zone, in contact with the rectal wall [26].

The prostate normally must be divided into regions or lines of ablation, which correspond to the focal length of the transducer. The transducer can be moved longitudinally and rotated 180° around the axis of the transducer so that the system can plan an ablation line in the longitudinal or transverse plane as long as it is at the same focal length. Although the focal length is fixed, it is possible to move the transducer, which is attached to a mechanical arm, in an antero-posterior direction to achieve the stacking of several treatment planes, making ablation of the entire gland possible.

Once the treatment is finished, the prostate tissue does not undergo immediate necrosis, but rather through a process of progressive ischemia that ends with coagulation necrosis several days after treatment. The thermal damage suffered by the tissue leads to edema and inflammation of the prostate, with an increase in the volume of up to 30% of its base value, this causes an incidence of acute urine retention between 1 and 20% of patients [27].

During this post-surgical period, it is necessary to perform a urinary diversion through a suprapubic or transurethral Foley catheter to ensure urinary drainage, during this time, it takes the prostate tissue to complete the sloughing phase, which is the elimination of necrotic tissue through the urethra, which happens between the first and fourth weeks after surgery; during this time the patient may complain of dysuria and urgency, in addition to obstructive symptoms. Outcomes and follow-up

In 2012, Blana et al., analyzed data from 9 European centers, where 1975 patients received whole gland ablation with HIFU (Ablatherm device): clinical stages T1/T2, 356 (18%) were classified as “complete HIFU patients”; 160 (44.9%) had low-risk cancer, 141 patients (39.6%) intermediate, 52 (14.6%) high risk and 3 (0.8%) were unclassified. 205 had a preHIFU TURP. The median PSA Nadir was 0.11 ng/mL (0.78–3.6 ng/mL), obtained at a mean of 14.4 weeks (3.2 months PO-HIFU). Negative biopsies were reported in 182 patients (80.5%): low risk group 86 (86%), intermediate risk 73 (78.5%), and high risk 23 (78.2%). The biochemical disease-free survival rates (DFSR) at 5 years were: low risk 49 cases (88%), intermediate 82 (40%), and high risk 11 (78%). At 7 years: low-risk group 22 (80%), intermediated 14 (82%), and high-risk 3 (64%) [28].

Crouzet reported in 2013: in 1002 patients treated in a single center the following: a median follow-up of 6.4 years. 392 patients received androgen deprivation therapy prior to HIFU, during a median duration of 4.3 months, to shrink the prostate, and it was stopped after HIFU in all cases.

PO-HIFU biopsies were done in 774 patients (77%), being negative in 485 (63%) and positive in 289 (37%). PSA Nadir was at ≤6 months PO-HIFU in all patients, with a median nadir of 0.14 ng/mL.

Biochemical recurrence (Phoenix definition) in 205 cases (21.2%). The biochemical free-survival rates at 5 and 8 years was: low risk 86−76%, intermediate risk 78−63%, and high-risk group 68–57%, respectively (p < 0.001). The overall BFSR at 10 years was 60%.

The adverse effects reported in this series were: urinary incontinence grade 2/3 from 6.4 to 3.1%, mostly managed conservatively and with physiotherapy (94.5%), requiring artificial sphincter in 3.4%, and suburethral sling in 2.1%. Bladder neck or urethral strictures, from 34.9 to 5.9%, resolved with cold knife incision or TURP. 3 patients required a urethral stent. Erections were preserved in 42.3% of patients with a baseline IIEF score ≥ 17 (<70 years: 55.6%; ≥ 70 years: 25.6% (p < 0.001). Rectourethral fistulas presented in 4 patients (0.4%) were related to repeated HIFU ablation [29].

Dickinson et al. reported medium-term results of 569 patients, in a multicenter study, where they received total gland ablation with HIFU as a treatment for localized prostate cancer, using the Sonablate 500 system.

They found that prostate ablation with HIFU is a treatment effective in cancer control in the medium term, with a 5-year relapse-free rate of 70%, with 87%, 63%, and 58% for low, intermediate, and high-risk groups, respectively. 29% required re-treatment with HIFU.

The adverse events reported were unique urinary tract infection in 58 of 754 (7.7%); repeated infection with epididymo-orchitis 22/754 (2.9%); rectourethral fistula 1/754 (0.13%); 183/754 (88%) continent; and form 236 patients with good erection prior to HIFU, 91 (39%) remained with good erections after HIFU. In the study, they concluded that HIFU is a repeatable outpatient treatment with good oncological control in localized cancer, with a low complication rate [30].

5.2.2 Focal therapy

“Focal therapy” and “partial gland ablation” are therapeutic options more frequently considered as good alternatives to treat localized prostate cancer, decreasing morbidity, seen more frequently after radical prostatectomy and external beam radiation.

According to an International Multidisciplinary Consensus on standardized nomenclature and surveillance methodologies, the definition of “focal therapy” describes “a guided ablation of an image-defined, biopsy-confirmed, cancerous lesion with a safety margin surrounding the targeted lesion” [31]. The therapeutic guided term “partial gland ablation” as stated by the consensus, is regional image-guided ablation based on biopsy location. This alternative therapy does not use the identification of lesions by imaging, but anatomical limits, trying to preserve functionality, with a complete tumor treatment. Included in the partial ablations are quadrant therapy, hemiablation, hockey stick, and subtotal ablation.

The main goal of focal therapies is to ablate the prostate cancer focus, with an adequate margin, considered 8 to 10 mm, to have a good oncological control, with preservation of the surrounding tissue, in order to decrease secondary morbidity common in more extensive treatments, maintaining a good quality of life, continence and erectile function.

The frequency of detection of localized prostate cancer has increased importantly with the routinary usage of PSA; since the refinement of the mpMRI of the prostate, and the updated PI RADS, the possibility of defining suspicious lesions is more reliable. Using this high definition T2-weighted MRI images in the fusion systems (Koelis, Artemis, etc.), have improved the precision in targeting smaller and localized cancers.

The description of the “index lesion”, is defined as the tumor lesion responsible for the biological behavior of prostate cancer. The panelist in the consensus, to standardize nomenclature, considered that all MRI-visible lesions with clinically significant cancer should be used as a target for Focal therapies [31, 32, 33]. All these parameters are suggested to be considered as decision-making guides to select patients for focal therapies or partial gland ablation. Focal therapy bases

It must be remarked, that focal therapy and partial gland ablation are not included in the AUA or EAU guidelines for the prostate cancer treatment, as a consequence we will base on the recommendations suggested in the expert consensus [31] to indicate them.

The clinically significant prostate cancer (CsPC) has been defined as prostate cancers with a volume more than 0.5 cc, or a T3 stage or major in a whole-mount specimen, and at least one core with Gleason score of 3 + 4 or 6, with core length more than 4 mm [34].

The detection of clinically significant prostate cancer (CsPC) has been facilitated with MRI-TRUS, in-bore MRI-targeted biopsy, and cognitive biopsy techniques. In systematic reviews, MRI-targeted biopsies demonstrated that CsPC detection was significatively more frequent than TRUS-guided biopsy, with the relative sensitivity of 1.16 (95% CI 1.02–1.32) compared with TRUS-guided biopsy [34, 35].

In a meta-analysis that included 16 studies with an accumulated number of 1926 patients, the rate of general detection of prostate cancer was similar between MRI-targeted biopsy (sensitivity, 0.85; 95% CI 0.80−0.89) and TRUS-guided biopsy (sensitivity, 0.81; 95% CI 0.70−0.88); in contrast to detection of CsPC by MRI-targeted biopsy, greater than TRUS-target biopsy (sensitivity 0.91; 95% CI 0.87−0.94 vs. 0.76; 95% CI 0.64−0.84), and a lower detection rate of insignificant cancer (sensitivity 0.44; 95% CI 0.26−0.64 vs. 0.83; 95% confidence interval 0.77−0.87, respectively) [36]. Selection of patients

Patient selection is a mandatory step to indicate a focal therapy or a partial gland ablation. As mentioned before, a precise image location of a lesion (PI RADS/LIKERT systems) and a pathology report of an index lesion; the agreement about index lesion (that of greater volume and pathology grade) capable of inducing the risk of prostate cancer progression.

The goal to treat the index lesion is to produce an acceptable oncologic control, decreasing morbidity preserving surrounding structures [32, 33]. The proposed selection criteria included: prostate-specific antigen (PSA) level < 10 ng/mL, no Gleason 4 or 5, the maximum length of cancer in each core of 7 mm, and less than 33% of positive cores [37]. In a multicenter study, reporting safety outcomes and complications, the selection criteria included: Gleason score ≤ 4 + 3 = 7b, if unilaterality, clinical stage T1 or T2, PSA levels - < 15 ng/mL, and life expectancy ≥10 years [38]. Planning

The definition to perform focal therapy or partial gland ablation depends on a good visualization of tumoral lesion, corroborated by pathology test, within limits of tumor volume that allows safe oncologic margins; in those cases, with multiple cancer lesions in the same parenchymal topography, the recommended treatment is a templated organ-preserving partial gland ablation, which in general uses urethra as anatomic landmark. Figure 7 defines focal and partial ablations [31].

Figure 7.

Differences between focal therapy and templated partial gland ablation. Focal therapy: Focused ablation of image-visible, biopsy-confirmed lesion(s) plus a safety margin. Quadrant ablation: Inclusion of all tissue within a quadrant of the prostate. Hemiablation: Inclusion of all tissue within a lateralized hemisphere of the prostate or the anterior half of the prostate. Hockey stick: Destruction of tissue within a lateralized hemisphere and anterior contralateral zone. Subtotal ablation: Inclusion of most of the parenchyma preserving the posterior lateral zone(s). The intention is to preserve at least one neurovascular bundle. Therapy

Treatment is accomplished using any of the two available commercial softwares: Focal-one or Sonablate, both systems can import standard DICOM MRI, to fuse and define the treatment zone, or as cognitive guidance.

Using high definition T2-weighted images as a guide, the prostate contour is done and the ROI section is marked, to be used in the HIFU system, the software allows through elastic fusion to match both MR and ultrasound images, to localize the suspicious lesion, and proceed with the therapy, customizing the number of zones, margins, and power to be used; limits and number of shots are defined automatically by the equipment, starting the treatment [15].

The validation of the treatment is done, in the FOCAL ONE system, once the therapy is finished, doing a CEUS volume, injecting microbubbles. The acquired volume shows very clearly the devascularized area. All sectors treated not showing enhancement after microbubbles injection are considered as entirely destroyed; when prostate sectors show enhancement, this tissue can be considered as living tissue (benign and malignant). The images obtained after CEUS can be fused in the initial planning sequence, showing the treated areas, and if needed new areas can be added to complete the ablation [15].

In the Sonablate system, two seconds immediately after sonication, the equipment scans, updating the prostate images in sagittal and axial, and a proprietary system measures the quality of RF caused in the treated tissue, giving a colorimetric scale: orange adequate energy delivered, yellow energy enough to destroy the tissue, green suboptimal energy delivered, and gray not measured.

This TCM system lets the physician replan those suboptimal or not measured spots and retreat, adjusting the energy to achieve the correct lesion. The second and more reliable procedure to validate the effectiveness of each shot, is the presence of cavitation, called “pop corn”, because the change of echogenicity, same as with TCM, 2 seconds after the sonication, the updated scan, shows in real-time the presence of a hyperechoic lesion, that must be evaluated, to control the power delivered, keeping it inside of the treatment box, as mentioned previously, the main goal is to cause extensive controlled cavitation in the treated tissue [39]. Post-HIFU evaluation

The suggested way to evaluate the treated zone, and the peripheral tissues, is Gadolinium-enhanced (non-dynamic) MRI. The immediate images reveal a central zone without enhancement that explains devascularization secondary to the coagulative necrosis, surrounded by an enhanced rim. After six months post-HIFU, a shrinkage of prostate volume is noticed (61% of median volume reduction), with a decrease of the signal intensity on T2-weighted images [15, 40]. Outcomes after focal HIFU

In 2018, Guillaumier S. et al., reported a 5-year outcomes study after focal therapy with HIFU. It was a prospective study including 625 patients with localized clinically significant prostate cancer. The study took place from January 1, 2006, to December 31, 2015, the inclusion criteria were: Gleason score 6−9, clinical-stage T1c-3bN0M0, prostate-specific antigen of ≤30 ng/mL.

All patients were followed for 3−6 months PSA, with mpMRI done at 1 year and 1−2 years the following years. All rises in PSA after nadir were evaluated with prostate biopsy or mpMRI, when suspicious with MRI-targeted biopsy. When clinically significant prostate cancer was found on biopsies, in field or out field, a repeat HIFU was offered. 599 patients completed at least 6 months follow-up, and 505 (84%) presented as intermediate of high-risk prostate cancer (D’Amico classification).

The Failure-free survival was: 1 year 99% (95% CI 98−100%), at 2 years 92% (95% CI 90−95%), and at 5 years88% (95% CI 85−91%). Kaplan–Meier estimated at 5 years for low risk 96% (95% CI 91−100%), intermediate risk 88% (95% CI 84–93%), and high risk group 84% (95% CI 78−90%). 8 patients opted for salvage radical prostatectomy, 36 salvage radiotherapy, and 1 androgen deprivation therapy. 10 patients progressed with metastases: Kaplan–Meier estimated for metastases-free survival: 1 year 99.7% (95% CI 99−100%), 3 years 99% (95% CI 98−100%), and 5 years 99% (95% CI 97−100%). Repeat focal HIFU: one done in 112, and two repeat HIFU in 9.56 patients out of 222, required biopsy after HIFU, secondary to PSA rise or mp MRI suspicion; 29 had in-field recurrence, 16 histological evidence of out-field cancer; and 11 patients both in and out-field cancer [41].

As described by Schmid, Schindele et al., in his multicenter study, included 98 men with localized low to intermediate risk prostate cancer, the parameters were median-PSA before HIFU of 6.5 ng/mL (1.03−14.9 ng/mL); clinical T stage ≥2 with cT1 in 76.5% (n = 75), cT2 in 23.5% (n = 23); Gleason score 3 + 3 = 6 in 17.3% (n = 17), 3 + 4 = 7a in 65.4% (n = 64), and 4 + 3 = 7b in 17.3% (n = 17); median prostate volume of 39.6 cc (21.6−135.2 cc); the treated index lesion volume of 10.5 cc (3.9−28.2 cc).

Their evaluation showed the following complications after HIFU therapy: 35 patients (35.7%) had adverse effects during the following 30 days after HIFU treatment with Clavien-Dindo grade ≥ II: 15 points (15.3%) with urinary tract infection and 26 patients (26.5%) with urinary retention. 4 patients (4.1%) needed another procedure (Clavien-Dindo grade IIIa/b). Late post HIFU complications, happening during days 30 to 90 was 2.0%. Considering the cancer location, the most common complications were those located at the anterior base in 50% of cases. When the urethra was ablated, the complications were present in 48.8% of cases (20 of 41), considered as a significant risk factor during the 30 days post-HIFU (odd ratio = 2.53; 95% confidence interval: 1.08−5.96; P = 0.033) [38].

5.2.3 Post external beam radiotherapy recurrences

Recurrence of prostate cancer after EBRT is a common condition, reported in up to 46% of patients treated with radiation. The therapeutic options used to control the progression are salvage prostatectomy, usually indicated in selected cases, because of technical difficulties, and higher morbidity; salvage cryotherapy, hormone blockage, and salvage HIFU. Biochemical recurrence (using PSA levels) in relation to the ASTRO-AUA-EAU guidelines, is a safe parameter to detect local recurrences, between 10−30% of cases. Extension studies must be included in the staging process, mpMRI and PET SCAN PSMA have shown excellent options to discard metastatic involvement.

Ideal patients considered as candidates for salvage HIFU must have PSA levels up to 2 ng/mL according to the ASTRO-Phoenix guidelines, correlated with extension studies as mpMRI or PET SCAN PSMA that will show suspicious tumors in the prostate, biopsy should be used as a confirmatory method; patients with metastatic involvement should be offered another type of procedure but HIFU. Additionally, candidates should have a Gleason score ≤ 8, and clinical-stage ≤T1-T3aNoMo.

Fulfillment of the guidelines can assure a better prognosis among prostate cancer patients treated with HIFU, since case selection is a determinant factor for a successful result, as described in a 2011 evaluation that was performed on a group of 84 men with biochemical failure after EBRT and a whole-gland salvage HIFU. Results have demonstrated that 93% of them were discharged within 23 hours following treatment, and only 20% (17 of 84 patients) needed an intervention for bladder obstruction. Within a follow-up of 19.8 months, 25% (21 of 84 patients) of the cohort presented a residual cancer detected on biopsy after salvage HIFU [42]. It is noteworthy that repeated HIFU procedures are a high-risk factor for rectal fistula development.

In a 2017 prospective study at University College London Hospitals and NHS Basingstoke Trust, in 150 men who received salvage HIFU between 2006 and 2015, the Kaplan–Meier overall survival at 60 months was 92% and among complications, UTI was 11.3% (17 of 150 patients) and bladder neck strictures of 8%. In addition, 87.5% remained pad-free at 2 years among those pad-free at baseline [43].


6. Conclusions

High-Intensity Focused Ultrasound or Focused Ultrasound Surgery is an emerging image-guided therapy for obstructive benign prostatic hyperplasia and prostate cancer.

With the advent of new methodologies in MRI, specifically multiparametric MRI; the possibility of fusioning the MR images in real-time ultrasound scans, changed the accuracy of targeting biopsies, and recently the therapy targeting to improve control of focalized lesions.

Recently, the usage of MRI guidance with EXABLATE and TULSA-PRO, taking advantage of thermometric scanning, allowed more accurate treatments, limited by the need for MRI facilities. In the case of whole gland ablation, it is compared in outcomes with radical prostatectomy and EBRT, with less adverse effects.

The most common consideration of less aggressive treatments for clinically significant prostate cancer made the focal therapy a growing alternative, only limited at this time for the availability of good technical mpMR images, necessary to assess accurately the parenchymal lesions. The general results in different centers make HIFU a highly promising therapeutic option.



Our deepest thanks to:

Prof. Narendra Sanghvi, Focus-Surgery and Sonablate Corp.

Alex Gonzalez, Sonablate Corp.

Rodrigo Chaluisan, Sonablate Corp. In memoriam.


Conflict of interest

The authors declare to use a Sonablate device for BPH and prostate cancer treatments, since 2005, participate in the proctoring teaching system of Sonablate Company and participate in a BPH protocol with Sonablate Company.


Video materials

All video materials referenced in this chapter are available to download here:


Acronyms and Abbreviations

PSAprostate-specific antigen
HIFUhigh intensity focused ultrasound
TURPtransurethral resection of prostate
BPHbenign prostate hyperplasia
mpMRImultiparametric magnetic resonance image
EBRTexternal beam radiotherapy


  1. 1. Lim KB. Epidemiology of clinical benign prostatic hyperplasia. Asian Journal of Urology. 2017;4(3):148-151. DOI: 10.1016/j.ajur.2017.06.004
  2. 2. Mearini L, Porena M. Transrectal high-intensity focused ultrasound for the treatment of prostate cancer: past, present, and future.Indian Journal of Urology.2010;26(1):4-11. DOI: 10.4103/0970-1591.60436
  3. 3. Newman PG, Rozycki GS. The history of ultrasound. Surgical Clinics of North America. 1998;78:179-195. DOI: 10.1016/S0039-6109(05)70308-X
  4. 4. Dalecki D. Mechanical bioeffects of ultrasound. Annual Review of Biomedical Engineering. 2004;6:229-248. DOI: 10.1146/annurev.bioeng.6.040803.140126
  5. 5. Zhou Y. High-Intensity Focused Ultrasound.Principles and Applications of Therapeutic Ultrasound in Healthcare. 1st ed. Boca Raton: CRC Press; 2016. pp. 245-292. DOI:
  6. 6. ter Haar G. High Intensity Focused Ultrasound Ablation of Pathological Tissue. Therapeutic Ultrasound. 1st ed. Switzerland: Springer; 2016. pp. 3-97. DOI: 10.1007/978-3-319-22536-4
  7. 7. Martin K, Ramnarine KV. Physics. Diagnostic Ultrasound Physics and Equipment. 3rd ed. Boca Raton, US: CRC Press; 2019. pp. 7-37. DOI: 10.1201/9781138893603
  8. 8. Duc NM, Huy HQ. A technical update of high-intensity focused ultrasound ablation for prostate Cancer and benign prostatic hyperplasia. Imaging in Medicine. 2018;10(5):139-142. DOI: 10.14303/Imaging-Medicine.1000115
  9. 9. Zhou Y-F. High intensity focused ultrasound in clinical tumor ablation.World Journal of Clinical Oncology.2011;2(1):8-27. DOI: 10.5306/wjco.v2.i1.8
  10. 10. Gelet A, Chapelon JY, Bouvier R, Souchon R, Pangaud C, Abdelrahim AF, et al. Treatment of prostate cancer with transrectal focused ultrasound: Early clinical experience. European Urology. 1996;29:174-178. DOI: 10.1016/s0929-8266(99)00005-1
  11. 11. Rewcastle JC. High intensity focused ultrasound for prostate cancer: A review of the scientific foundation, technology and clinical outcomes. Technology in Cancer Research & Treatment. 2006;5(6):619-625. DOI: 10.1177/153303460600500610
  12. 12. Pickles T, Goldenberg L, Steinhoff G. Technology review: High-intensity focused ultrasound for prostate cancer. The Canadian Journal of Urology. 2005;12(2):2593-2597
  13. 13. Tsakiris P, Thüroff S, de la Rosette J, Chaussy C. Transrectal high-intensity focused ultrasound devices: A critical appraisal of the available evidence. Journal of Endourology. 2008;22(2):221-229. DOI: 10.1089/end.2007.9849
  14. 14. Crouzet S, Rouviere O, Lafond C, et al. Focal high-intensity focused ultrasound (HIFU). In: Barret E, Durand M, editors. Technical Aspects of Focal Therapy in Localized Prostate Cancer. 1st. ed. Paris: Springer; 2015. pp. 137-151. DOI: 10.1007/978-2-8178-0484-2. ch12
  15. 15. Uchida T, Shoji S, Nakano M, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: Eight-year experience. International Journal of Urology. 2009;16(11):881-886. DOI: 10.1111/j.1442-2042.2009.02389.x
  16. 16. Illing R, Emberton M. Sonablate-500: Transrectal high-intensity focused ultrasound for the treatment of prostate cancer. Expert Review of Medical Devices. 2006;3(6):717-729. DOI: 10.1586/17434440.3.6.717
  17. 17. Napoli A, Anzidei M, De Nunzio C, et al. Real-time magnetic resonance-guided high-intensity focused ultrasound focal therapy for localised prostate cancer: Preliminary experience. European Urology. 2013;63(2):395-398. DOI: 10.1016/j.eururo.2012.11.002
  18. 18. Profound Medical 2021 [Internet] Available from:
  19. 19. Klotz L, Pavlovich CP, Chin J, et al. Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate Cancer. The Journal of Urology. 2021;205(3):769-779. DOI: 10.1097/JU.0000000000001362
  20. 20. Lumiani A, Samun D, Sroka R, Muschter R. Single center retrospective analysis of fifty-two prostate cancer patients with customized MR-guided transurethral ultrasound ablation (TULSA). Urologic Oncology. 2021;39(12):830.e9-830.e16. DOI: 10.1016/j.urolonc.2021.04.022
  21. 21. Rosier PF, de Wildt MJ, Wijkstra H, Debruyne FF, de la Rosette JJ. Clinical diagnosis of bladder outlet obstruction in patients with benign prostatic enlargement and lower urinary tract symptoms: Development and urodynamic validation of a clinical prostate score for the objective diagnosis of bladder outlet obstruction. The Journal of Urology. 1996;155(5):1649-1654
  22. 22. Ebert T, Graefen M, Miller S, Saddeler D, Schmitz-Dräger B, Ackermann R. High-intensity focused ultrasound (HIFU) in the treatment of benign prostatic hyperplasia (BPH). The Keio Journal of Medicine. 1995;44(4):146-149. DOI: 10.2302/kjm.44.146
  23. 23. Madersbacher S, Schatzl G, Djavan B, Stulnig T, Marberger M. Long-term outcome of transrectal high- intensity focused ultrasound therapy for benign prostatic hyperplasia. European Urology. 2000;37(6):687-694. DOI: 10.1159/000020219
  24. 24. Cranston D, Leslie T, ter Haar G. A review of high-intensity focused ultrasound in urology. Cancers. 2021;13(22):5696. DOI: 10.3390/cancers13225696
  25. 25. Ziglioli F, Baciarello M, Maspero G, et al. Oncologic outcome, side effects and comorbidity of high-intensity focused ultrasound (HIFU) for localized prostate cancer. A review. Annals of Medicine and Surgery. 2020;56:110-115. DOI: 10.1016/j.amsu.2020.05.029
  26. 26. Crouzet S, Murat FJ, Pasticier G, Cassier P, Chapelon JY, Gelet A. High intensity focused ultrasound (HIFU) for prostate cancer: Current clinical status, outcomes and future perspectives. International Journal of Hyperthermia. 2010;26(8):796-803. DOI: 10.3109/02656736.2010.498803
  27. 27. Mearini L, Nunzi E, Giovannozzi S, Lepri L, Lolli C, Giannantoni A. Urodynamic evaluation after high-intensity focused ultrasound for patients with prostate Cancer. Prostate Cancer. 2014;2014:1-7. DOI: 10.1155/2014/462153
  28. 28. Blana A et al. Complete high-intensity focused ultrasound in prostate cancer: Outcome from the @-registry. Prostate Cancer and Prostatic Diseases. 2012;15:256-259. DOI: 10.1038/pcan.2012.10
  29. 29. Crouzet S et al. Whole-gland ablation of localized prostate Cancer with high-Intesity focused ultrasound: Oncologic outcomes and morbidity in 1002 patients. European Urology. 2014;65(5):907-914. DOI: 10.1016/j.eururo.2013.04.039
  30. 30. Dickinson L, Arya M, Afzal N, Cathcart P, Charman SC, Cornaby A, et al. Medium-term outcomes after whole-gland high-intensity focused ultrasound for the treatment of nonmetastatic prostate Cancer from a multicentre registry cohort. European Urology. 2016;70(4):668-674. DOI: 10.1016/j.eururo.2016.02.054
  31. 31. Lebastchi AH, George AK, Polascik TJ, et al. Standardized nomenclature and surveillance methodologies after focal therapy and partial gland ablation for localized prostate Cancer: An international multidisciplinary consensus. European Urology. 2020;78(3):371-378. DOI: 10.1016/j.eururo.2020.05.018
  32. 32. Connor MJ, Gorin MA, Ahmed HU, Nigam R. Focal therapy for localized prostate cancer in the era of routine multi-parametric MRI. Prostate Cancer and Prostatic Diseases. 2020;23(2):232-243. DOI: 10.1038/s41391-020-0206-6
  33. 33. Ahmed HU, Dickinson L, Charman S, et al. Focal ablation targeted to the index lesion in multifocal localised prostate Cancer: A prospective development study. European Urology. 2015;68(6):927-936. DOI: 10.1016/j.eururo.2015.01.030
  34. 34. Shoji S, Hiraiwa S, Ogawa T, et al. Accuracy of real-time magnetic resonance imaging-transrectal ultrasound fusion image-guided transperineal target biopsy with needle tracking with a mechanical position-encoded stepper in detecting significant prostate cancer in biopsy-naïve men. International Journal of Urology. 2017;24(4):288-294. DOI: 10.1111/iju.13306
  35. 35. Shoji S. Magnetic resonance imaging-transrectal ultrasound fusion image-guided prostate biopsy: current status of the cancer detection and the prospects of tailor-made medicine of the prostate cancer. Investigative and Clinical Urology. 2019;60(1):4-13. DOI: 10.4111/icu.2019.60.1.4
  36. 36. Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MG. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: A systematic review and meta-analysis. European Urology. 2015;68(3):438-450. DOI: 10.1016/j.eururo.2014.11.037
  37. 37. Barret E, Durand M. Technical Aspects of Focal Therapy in Localized Prostate Cancer. France: Springer-Verlag; 2015. DOI: 10.1007/978-2-8178-0484-2
  38. 38. Schmid FA, Schindele D, Mortezavi A, et al. Prospective multicentre study using high intensity focused ultrasound (HIFU) for the focal treatment of prostate cancer: Safety outcomes and complications. Urologic Oncology. 2020;38(4):225-230. DOI: 10.1016/j.urolonc.2019.09.001
  39. 39. Sanghvi NT, Chen WH, Carlson R, et al. Clinical validation of real-time tissue change monitoring during prostate tissue ablation with high intensity focused ultrasound. Journal of Therapeutic Ultrasound. 2017;5:24. DOI: 10.1186/s40349-017-0102-2
  40. 40. Kirkham AP, Emberton M, Hoh IM, Illing RO, Freeman AA, Allen C. MR imaging of prostate after treatment with high-intensity focused ultrasound. Radiology. 2008;246(3):833-844. DOI: 10.1148/radiol.2463062080
  41. 41. Guillaumier S et al. A Multicenter study of 5-year outcomes following focal therapy in treating clinically significant Nonmetastasic Prostae Cancer. European Urology. 2018;74(4):422-429. DOI: 10.1016/j.eururo.2018.06.006
  42. 42. Uddin Ahmed H, Cathcart P, Chalasani V, et al. Whole-gland salvage high-intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy. Cancer. 2012;118(12):3071-3078. DOI: 10.1002/cncr.26631
  43. 43. Kanthabalan A, Peters M, Van Vulpen M, et al. Focal salvage high-intensity focused ultrasound in radiorecurrent prostate cancer. BJU International. 2017;120(2):246-256. DOI: 10.1111/bju.13831

Written By

Carlos M. Garcia-Gutierrez, Habid Becerra-Herrejon, Carlos A. Garcia-Becerra and Natalia Garcia-Becerra

Submitted: December 28th, 2021 Reviewed: January 13th, 2022 Published: March 8th, 2022