High-intensity focused ultrasound (HIFU) is a therapeutic procedure in uro-oncology that can be used in the treatment of prostate cancer, among other diseases. The application of high-intensity focused ultrasound enables the targeted destruction of tissue from a distance under real-time control by using MRI (magnetic resonance imaging). In recent years, the number of studies on the use of HIFU for the treatment of prostate cancer has been increasing, making it possible to assess the benefits and risks of the procedure. The use of high-intensity focused ultrasound has been performed in Germany since 1996.According to the S3 guideline, the procedure is considered an experimental procedure in localized prostate carcinoma.
Indications (areas of application)
- Age over 60 years – the use of high-intensity focused ultrasound should only be used in patients who are older than 60 years and surgical removal of the prostate would not be indicated, for example, because of a reduced general condition.
- Contraindications for radical prostatectomy (surgical removal of prostate gland with capsule, the terminals of the vas deferens, seminal vesicles and regional lymph nodes) – age, concomitant diseases, etc.
- Localized tumor – currently, the application of the procedure is carried out only in prostate carcinoma with the degree of extension T1 or T2 of the primary tumor. Tumor stage T1 is characterized by the fact that the tumor is not manually palpable and thus can only be detected during a biopsy. In tumor stage T2, there is tumor spread within the prostate capsule.The treatment of prostate carcinomas with a higher degree of expansion is possible if necessary, but not listed as a standard indication.
- Gleason score ≤ 7 – the Gleason score (see also under classification of prostate cancer) is used for the histological (fine tissue) assessment of a prostate carcinoma, whereby the material for the examination is taken by a punch biopsy from the prostate.The Gleason score itself represents an important prognostic factor in prostate cancer. A Gleason score below 7 indicates a well or moderately differentiated tumor. Tumors with a higher Gleason score have a tendency to grow more rapidly and aggressively.
- PSA value < 20 ng/ml (better: < 15 ng/ml).
- Defined prostate size – sonography is used to determine the AP diameter of the prostate (prostate AP diameter), although this diameter is limited to 2.5 cm for indication. Furthermore, the prostate volume (TRUS) for performing the procedure is limited to 30 cm³ (because otherwise the ventral (abdominal) prostate areas are not reached with HIFU therapy). However, there is the possibility, including hormone treatment, to achieve a reduction in the size of the prostate.
Contraindications
- Prostate volume ≥ 30 cm³.
- Calcifications of the prostate tissue visible in ultrasound. These can lead to irregular reflex zones of the ultrasound beam (with unpredictable side effects such as fistula formation in the rectal area / rectum).
- In the condition following a fistula in the treatment area.
- Patients with absent rectum or active inflammatory bowel disease.
- Patients with tumor infiltration into the rectum (rectal) due to prostate cancer.
Note!The treatment of prostate carcinoma using the HIFU method is not yet covered by the S-3 guideline on the treatment of prostate carcinoma.
Before therapy
- Diagnostics and medical history – for the treatment of prostate cancer, the tumor present must first be assessed. Depending on various parameters such as the tumor stage but also a possible systemic infestation (tumor cells wash out and form metastases) – e.g. osseous metastases (bone metastases) – the therapy must be adapted to the present findings (staging according to the TNM classification).
- Spinal anesthesia – the HIFU is performed under spinal anesthesia (administration of an anesthetic drug into the cerebrospinal fluid space), with the patient positioned in the right lateral position.
The procedure
The high-intensity and high-energy focused ultrasound causes local tissue destruction.This results in a change in the biological structure of the cell. The effect on the target cell is due to mechanical, thermal and cavitation effects (formation of cavities). The temperature increase in the target tissue can cause necrosis (tissue death), which is irreversible (non-recoverable) tissue damage. The use of high-intensity focused ultrasound results in a significant reduction in PSA (prostate-specific antigen) levels in the first year after treatment, in addition to detectable tissue destruction. However, follow-up studies are lacking for the assessment of long-term PSA levels.The effect of ultrasound on target cells (tumor cells) has been demonstrated in studies. In all patients, histological examination of prostate tissue samples showed complete necrotization of the target tissue. Performance of high-intensity focused ultrasound for the treatment of local prostate carcinoma
After anesthesia is given, transrectal ultrasound of the prostate (TRUS) is used to obtain a transverse and longitudinal prostate section. The bladder neck is then defined as the treatment endpoint. After defining a safety distance of 3-6 mm between the rectal mucosa (mucosal layer) and the posterior portion of the prostate capsule, the tissue in the defined treatment area is destroyed by the high-intensity focused ultrasound. To date, two HIFU devices have been developed and used to perform the procedure. The Ablatherm represents a treatment table with integrated HIFU technology, which can be used for HIFU therapy as well as for ultrasound diagnostics. The measurement of various parameters such as rectal temperature and the automatic comparison with the created therapy planning model ensure not only a high therapeutic effectiveness but also a low error rate. The Sonablate can also be used to perform HIFU and consists of, among other things, a technique module and a cooling module. Survival rates with the application of high-intensity focused ultrasound
Initial studies have shown that in the setting of localized prostate cancer and lack of eligibility for radical prostatectomy, the 5-year survival rate for a Gleason score of 2-6 could be increased from 76.9% to 85.4% with the use of high-intensity focused ultrasound. In the world’s largest multicenter study of high-intensity focused ultrasound (HIFU) in patients (n = 625) with nonmetastatic prostate cancer and a Gleason score of 6 to 9 to stage T1c-3bN0M0, in whom prostate-specific antigen (PSA) was not allowed to rise above 30 ng/ml, recurrence was rare after five years and most patients remained free of erectile dysfunction (ED; Prevalence (disease incidence): 15%) and urinary incontinence (98 percent of all patients off without inserts after surgery). Three parameters must be considered to assess treatment success:
- Histological control – with the help of a biopsy, a tissue sample is taken from the prostate, so that the presence of a tumor within the prostate can be excluded.
- PSA value – based on the PSA value determined in the patient’s blood, statements can be made for the follow-up treatment of the tumor.
- Bone scintigram – with the help of scintigraphic imaging of the skeletal system can be determined to what extent the primary tumor has metastasized in the skeletal system. In a systemic tumor therapy with additional therapeutic measures in the context of chemotherapy, a regression of metastases can also be shown with the bone scintigram.
Advantages and disadvantages of high-intensity focused ultrasound compared with radical prostatectomy
Advantages
- High-intensity focused ultrasound (HIFU) represents a procedure that achieves passable cure rates compared with radical prostatectomy (radical removal of the prostate), but it has significantly fewer side effects and fewer complications because, among other things, there is no surgical risk and general anesthesia is not required.The cure rates are highly dependent on the initial stage of the disease. Taking into account the above indications, the probability of a 5-year freedom from biochemical recurrence (recurrence of the disease) is estimated at about 40-60%.
- The use of high-intensity focused ultrasound continues to hold open the possibility of using an additional therapeutic procedure.
- The option of prior local ablation of prostate cancer (transurethral resection of the prostate, TUR; TUR-P; also called debulking-Tur-P – requires about 5 days of inpatient stay – thereafter, at an interval of 4-6 weeks, HIFU therapy is performed) because of too large prostate (≥ 30 cm³) represents an additional indication for the use of ultrasound procedure, in addition to the therapy of organ-confined disease. These concern local recurrences (recurrence of the tumor) after radiotherapy (radiation therapy) or early hormonal ablation (medical castration, 10%) and additional local reduction of tumor mass in combination with hormonal ablation (10%). The use of the procedure allows both curative (cure as a goal) and palliative (palliation) objectives.
Disadvantages
- High-intensity focused ultrasound (HIFU) represents a procedure that achieves passable cure rates compared to radical prostatectomy, but has significantly fewer side effects and complications, including no surgical risk and no need for general anesthesia.Cure rates are highly dependent on the initial stage of the disease. Taking into account the above indications, the probability of a 5-year freedom from biochemical recurrence is about 40-60%.
- To date, it is relatively unclear to what extent high-intensity focused ultrasound can influence the tolerability of other following therapeutic procedures. If necessary, a combination with radiotherapy could lead to a higher rate of ureteral stenosis (narrowing). However, follow-up studies for long-term assessment of all complications are lacking for precise assessment.
- Necrotization (death) of prostate tissue may potentially complicate follow-up surgery, which could also increase the rate of complications.
After therapy
The therapeutic procedure does not impose a serious burden on the body, so no post-therapy measures are necessary. However, the success must be evaluated using various diagnostic methods at several points in time.
Possible complications
- Urinary tract infections (UTIs) – during high-intensity focused ultrasound, infections may occur, especially in the lower urinary tract. Urinary tract infection is the most common complication of HIFU (8-50%).
- Epididymitis (inflammation of the epididymis) (rare) – usually due to an ascending (ascending) bladder or prostate infection.
- Bladder neck stenosis (about 20%) – bladder neck stenosis is the inability of the involuntary (internal) bladder sphincter; symptoms of bladder neck stenosis are the “blockage of the bladder neck”, which leads to difficult urination.
- Bladder neck sclerosis (about 2-3%) – these sometimes require surgical bladder neck incision.
- Stress incontinence (formerly: stress incontinence) – the occurrence of stress incontinence is a non-negligible complication of the procedure, which can occur in 1-24% of cases.
- Rectal redness – this complication rarely occurs (1-15%), depending on the experience of the treating physician.
- Fistula – a fistula is a non-naturally occurring connection between a hollow organ and another organ or organ surface. However, the occurrence of a fistula is very rare (0.1-3%).
- Erectile dysfunction (ED; erectile dysfunction) – these are reported in terms of reduction in erectile function with up to 50% of cases.
