Medical Policy: 02.01.53
Original Effective Date: March 2014
Reviewed: January 2018
Revised: January 2018
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
This medical policy is addressing high intensity focused ultrasound (HIFU). For magnetic resonance (MR) guided focused ultrasound (MRgFUS), see medical policy 04.01.09 MRI Guided High-Intensity Focused Ultrasound (MRgFUS) Ablation.
High intensity focused ultrasound (HIFU) is a minimally-invasive technique that is currently under clinical study for treatment of cancers and other conditions, including but not limited to prostate cancer, renal cancer (kidney cancer), pancreatic cancer, breast cancer, brain cancer, soft tissue sarcomas, treatment of primary and secondary liver cancer, thyroid nodules, benign prostatic hypertrophy (BPH) and breast fibroadenoma. Currently, the primary area of study is for use in the treatment of prostate cancer.
High intensity focused ultrasound (HIFU) focuses high-energy ultrasound waves on a single location, which increases the local tissue temperature to over 80 degrees celcius. This causes a discrete locus of coagulative necrosis of approximately 3x3x10 mm. HIFU can be repeated if necessary. This procedure is typically carried out in an outpatient setting and is performed under a spinal or general anesthesia. A proposed benefit to this method is less adjacent tissue damage.
Methods to manage localized prostate cancer include watchful waiting and active surveillance. Treatment options for localized prostate cancer include radical prostatectomy, radiotherapy (EBRT or brachytherapy) and whole gland cryotherapy. High intensity focused ultrasound (HIFU) has been proposed as a method for treating localized prostate cancer. For treatment of the prostate the physician uses a transrectal probe to plan, perform and monitor treatment in real time sequence to ablate the entire gland or small discrete lesions. A cooling balloon surrounding the probe protects the rectal mucosa from the high temperature. Reported post procedure complications include incontinence, bladder neck/urethral stricture and rectourethral fistulae.
In 2016, the Agency for Healthcare Research and Quality (AHRQ) issued a clinician research summary regarding therapies of clinically localized prostate cancer which concluded the evidence is insufficient to permit conclusions about the comparative effectiveness or adverse effects of all other treatments including brachytherapy, cryotherapy, intensity modulated radiation therapy, proton beam radiation therapy, stereotactic body radiation therapy and high intensity focused ultrasound compared in this review. This summary concluded that evidence from two large studies (the SPCG-4 study and PIVOT) showed that metastases can be reduced with radical prostatectomy versus watchful waiting. Evidence related to the comparative effectiveness of radical prostatectomy and watchful waiting for mortality outcomes was rated as insufficient, largely because of the lack of replication in the two large trials. Evidence for other therapies for clinically localized prostate cancer assessed in this updated systemic review is too limited to determine their comparative effectiveness and adverse effects. Evidence is insufficient to determine which subgroups of patients might benefit most from these therapies based on patient disease characteristics. Clear guidance regarding the appropriate patient population for radical prostatectomy, radiation therapy, hormonal therapy, watchful waiting, active surveillance, or one of the other options is difficult to establish. Physicians might take into consideration age, general health status, stage of tumor, PSA level. Gleason score, logistical factors (timing of survery vs radiation therapy), use of androgen deprivation therapy (ADT) as a component of the treatment strategy, patient preferences, nuances in patient recovery and quality of life, and other factors in identifying the most appropriate treatment options. Guidelines from NCCN and the American Urological Association may be informative in this regard.
Based on review of the peer reviewed medical literature for high intensity focused ultrasound (HIFU) and the treatment of localized prostate cancer the literature consists for non-randomized studies, systemic reviews and case series. HIFU may provide quality of life (QOL) advantages for patients in comparison to surgery and radiotherapy, however, there is a lack of consensus on objective response criteria, very limited long-term oncologic data, and no comparative effectiveness data versus traditional treatments available for localized prostate cancer. The long term efficacy, safety and long-term health outcomes of HIFU for the treatment of localized prostate cancer has not been established in controlled clinical trials. Well-designed prospective comparative studies are needed to evaluate risk/benefit of HIFU for the treatment of localized prostate cancer. The American Urological Association (AUA), American Society of Radiation Oncology (ASTRO) and Society of Urologic Oncology (SUO) issued a guideline in 2017 on clinically localized prostate cancer which states “the Panel recommends if HIFU is offered as an alternative treatment modality for localized prostate cancer, it should be done within the context of a clinical trial and clinicians should inform patients considering focal therapy or HIFU that these treatment options lack robust evidence of efficacy”. The evidence is insufficient to determine the effects on net health outcomes.
Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland. Symptoms of BPH include frequent urination, urgency and excessive urination at night. Drug therapy may benefit patients with mild symptoms. Transurethral resection of the prostate has been established as the standard treatment for moderate to severe BPH. HIFU is one of several less invasive alternatives to surgical resection of the prostate that are currently under clinical study. HIFU delivers targeted high intensity ultrasound that rapidly elevates the temperature in a precise focal zone, thereby ablating excess prostate tissue.
Evidence in the peer reviewed medical literature evaluating HIFU for BPH consists primarily of few case series studies, and therefore, there is insufficient evidence in the peer reviewed medical literature to draw conclusions regarding the safety and efficacy of high intensity focused ultrasound (HIFU) for the treatment of benign prostatic hypertrophy (BPH). Currently no society guidelines include HIFU as a management modality for BPH. The evidence is insufficient to determine the effects on net health outcomes.
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. The only potentially curative treatments are surgical resection and liver transplantation. The majority of patients with primary or metastatic liver cancers are not suitable candidates for surgical resection at the time of diagnosis. In addition, chemotherapy and radiotherapy rarely produce a complete or sustained response in patients with advanced disease. High intensity focused ultrasound (HIFU) is under investigation for the ablation of unresectable HCC.
Based on review of the peer reviewed medical literature HIFU for the treatment of hepatocellular carcinoma (HCC) the literature includes nonrandomized controlled trials, retrospective cohort study and case series studies with small patient populations. The overall quality of evidence is low due to the lack of randomized controlled trials, and of studies comparing HIFU to other standard treatment modalities. Other limitations included differences between studies in patient characteristics (e.g. tumor size and disease severity), measure of tumor response and length of follow-up also impacted the quality of available evidence. Additional well-designed studies with larger patient populations to include comparative studies are needed to support the safety and effectiveness of high intensity focused ultrasound (HIFU) for the treatment of unresectable hepatocellular carcinoma (HCC). The evidence is insufficient to determine the effects on net health outcomes.
Renal cell carcinoma (RCC), also referred to as kidney cancer is a disease in which cancer cells are found in the lining of the tubules in the kidney. Symptoms of renal cell carcinoma may include: blood in the urine, loss of appetite, pain in the side that doesn’t subside, weight loss and anemia. Standard treatment available for patients with RCC includes surgery, chemotherapy, external or internal radiation therapy, and immunotherapy. Surgical excision in the form of a simple or radical nephrectomy is the accepted, often curative, treatment for stages I, II and III of RCC. HIFU has been proposed as an intervention for small renal masses as well as advanced stage renal malignancy.
Based on the review of the peer reviewed medical literature there are a small amount of studies, primarily case series with small patient populations and insufficient data to draw conclusions. The safety and effectiveness of the use of high intensity focused ultrasound (HIFU) for the treatment of renal cancer has not been established. The evidence is insufficient to determine the effects on net health outcomes.
Based on the review of the peer reviewed medical literature there have been isolated case series studies published utilizing high intensity focused ultrasound (HIFU) to treat indications such as brain, breast and pancreatic cancers. The evidence is insufficient to make any determinations regarding safety and effectiveness for the use of HIFU for these indications. The evidence is insufficient to determine the effects on net health outcomes.
Based on the review of the peer reviewed medical literature well designed studies comparing high intensity focused ultrasound (HIFU) to cryotherapy, radiofrequency ablation, and/or external beam radiotherapy are needed to ascertain the effectiveness of HIFU for the treatment of bone metastases. HIFU may provide another treatment option for patients with primary bone tumors who are not surgical candidates or who refuse surgery, but this data needs to be confirmed as well. The evidence is insufficient to determine the effects on net health outcomes.
Breast fibroadenoma (FA) is a benign tumor, most often detected during self-examination or clinical breast examination. Usually occurring in geno typical women under the age of 30, they are seen in approximately 10% of all geno typical women during their lifetime. FA account for between 30% and 75% of all breast biopsies, depending on the age of the population being sampled. Because of the superficial location, breast FA is suitable for minimally invasive ablation techniques. These techniques can be divided into heat based modalities which include high-intensity focused ultrasound (HIFU), radiofrequency ablation, laser ablation and cryoablation. Based on the review of the peer reviewed medical literature further studies with longer follow up are needed to establish the optimal treatment protocol and to assess the long term efficacy of HIFU for this indication. The evidence is insufficient to determine the effects on net health outcomes.
Nodular thyroid tissue is common, however most thyroid nodules are benign. Causes of benign thyroid nodules include goiter and Hashimoto’s thyroiditis. The incidence of malignancy, or thyroid cancer, depends on factors such as age, gender, radiation exposure and family history. Treatment of thyroid cancer depends on the type of cancer, but may include one or more of the following treatments: radioiodine, thyroid hormone suppression and surgical removal of the thyroid gland. Minimally invasive treatments, such as percutaneous ethanol injection sclerotherapy, laser photocoagulation, and high intensity focused ultrasound (HIFU) ablation have been proposed as an alternative to surgery.
Based on the review of the peer reviewed medical literature there are limited studies, primarily case series with small patient populations. These studies suggest that high intensity focused ultrasound (HIFU) may be promising non-invasive tool for nodular thyroid disease, but the available evidence is insufficient data to draw conclusions regarding HIFU for this indication. The evidence is insufficient to determine the effects on net health outcomes.
Based on review of the peer reviewed medical literature the long term efficacy and safety of high intensity focused ultrasound (HIFU) compared to established interventions for various conditions have not been proven in controlled clinical trials for any indication. Additional randomized clinical trials with larger patient populations comparing established interventions are needed to determine the role of HIFU. Currently there are no society guidelines that indicate the use of HIFU as a treatment modality. The evidence is insufficient to determine the effects on net health outcomes.
Other Local Therapies: Local therapies have been investigated for the treatment of localized prostate cancer in the initial disease and recurrent settings, with the goals of reducing side effects and matching the cancer control of therapies. At this time, the panel recommends only cryosurgery and high intensity focused ultrasound (HIFU) as options for radiation therapy recurrence in the absence of metastatic disease.
In 2017, the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO) and Society of Urologic Oncology (SUO) issued a guideline on clinically localized prostate cancer, which included the following guideline statements regarding high intensity focused ultrasound (HIFU):
Care Options by Cancer Severity/Risk Group
The Panel recommends that if HIFU is offered as an alternative treatment modality for localized prostate cancer, it should be done within the context of a clinical trial. Prospective randomized or comparative trials with other treatment modalities are lacking. Published five year oncologic outcomes are variable and attributable to the lack of consensus on objective response criteria. Whole prostate ablation utilizing HIFU with or without short term ADT has been associated with a comparable incidence of post treatment incontinence, bladder neck/urethral stricture and rectouretheral fistulae.
Future Directions: Well-designed prospective studies are needed to evaluate the risk/benefit of ablative techniques (e.g. HIFU or focal ablative treatment).
In 2010 (reviewed and validity confirmed 2014) , the American Urological Association issued a guideline on the management of benign prostatic hyperplasia (BPH) which does not indicate or include the use of high intensity focused ultrasound in the management of benign prostatic hypertrophy.
The 2011 American College of Radiology Expert Panel on Radiation Oncology-Prostate Work Group’s guideline on locally advanced (high risk) prostate cancer does not mention the use of HIFU in the list of treatment options. The summary states that HIFU is currently an experimental therapy.
In 2016, American College of Radiology Expert Panel on Radiation Oncology-Prostate Work Group’s guideline on locally advanced high risk prostate cancer was updated and states, “Ablative treatments including cryotherapy and high-intensity focused ultrasound (HIFU) are other options available to men with high-risk prostate cancer, though data are limited for these modalities. There was insufficient literature using parameters employed for these modalities to be included in the assessment of high-risk prostate cancer”.
The panel did not include other treatment options i.e. ablative treatments cryotherapy and high intensity focused ultrasound (HIFU) in their summary of recommendations.
NICE also issued guidance on the use of focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer in 2012. It concluded that current evidence on HIFU for localized prostate cancer raises no major safety concerns. However, evidence on efficacy is limited in quantity, with concern that prostate cancer is commonly multifocal. Therefore this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.
In October 2015, the Sonablate 450 (SonaCare Medical) was approved by FDA through a de novo request and classified the device as class II under the generic name “high intensity ultrasound system for prostate tissue ablation”. This device was the first of its kind to be approved in the United States. A similar device, Ablatherme (EDAP TMS), was cleared for marketing by FDA through the 510(k) process shortly thereafter.
See also medical policies 04.01.09 MRI-Guided High-Intensity Focused Ultrasound (MRgFUS) Ablation or 07.01.69 Treating Benign Prostatic Hyperplasia
High Intensity Focused Ultrasound (HIFU) is considered investigational for all indications including but not limited to the following:
Based on the review of the peer reviewed medical literature the long term efficacy and safety of high intensity focused ultrasound (HIFU) compared to established interventions for various conditions has not been proven in controlled clinical trials for any indication. Additional randomized clinical trials with larger patient populations comparing established interventions are needed to determine the role of HIFU. Currently there are no society guidelines that indicate the use of HIFU as a treatment modality. The evidence is insufficient to determine the effects on net health outcomes.
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
*CPT® is a registered trademark of the American Medical Association.