Latest Review Date: August 2024

Category: Surgery                                                      

POLICY:

The use of ultrasound-guided high-intensity focused ultrasound (hifu) ablation is considered investigational for all indications, including but not limited to the following conditions, due to the lack of clinical evidence demonstrating an impact on improved health outcomes:

• Prostate cancer;
• Liver cancer;
• Grave's disease.

DESCRIPTION OF PROCEDURE OR SERVICE:

Ultrasound-guided high-intensity focused ultrasound (HIFU) ablation is a minimally invasive technique that delivers intense ultrasound energy with subsequent heat destruction of tissue at a specific focal distance from the probe. A proposed benefit of this treatment is that it allows treatment of a tumor without damaging intervening and surrounding tissue, eliminating the need for incisions and possibly shortening healing time. Ultrasound-guided HIFU has been investigated for treatment of several different types of tumors, particularly prostate cancer.

In the prostate cancer setting, ultrasound-guided HIFU is being studied as primary treatment of clinically localized prostate cancer, as well as salvage therapy after radical prostatectomy and external-beam radiation therapy. It may be used alone or in conjunction with transurethral resection of the prostate (TURP). Under ultrasound guidance, the HIFU probe is inserted transrectally to the prostate gland where it emits a precise ultrasound beam and generates a sudden temperature increase that destroys the targeted tissue. The procedure takes one to three hours to complete.

In 2015, the Sonablate® 450 was approved by the FDA through a de novo request as a class II device 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, Ablatherm® was cleared for marketing by the FDA through the 510(k) process shortly thereafter.

KEY POINTS

Summary of Evidence

The evidence for high-intensity focused ultrasound (HIFU) ablation for treatment of cancer and other conditions consists primarily of case series and small non-randomized comparative trials. The long-term safety and efficacy of HIFU compared to other established treatments for various cancer diagnoses such as prostate, kidney, liver, and pancreatic cancer, as well as additional conditions, has not been proven in the literature. Additional randomized controlled trials and comparative studies are needed to better determine the effect of this technology on health outcomes.

In the context of prostate cancer, high-intensity focused ultrasound (HIFU) ablation uses sonic waves to create thermal energy that destroys target tissue within the prostate. HIFU has not been compared with other standard treatment approaches in randomized trials, nor is it included in guidelines for the initial management of men with prostate cancer from expert groups. HIFU is also being investigated for treatment of other cancers and conditions, including but not limited to the following: kidney, liver, and pancreatic cancer; placenta accreta, Grave’s disease, and more.

In 2015, the Sonablate® 450 was approved by the FDA through a de novo request as a class II device 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, Ablatherm® was cleared for marketing by the FDA through the 510(k) process shortly thereafter. Although HIFU is approved by the US Food and Drug Administration (FDA) for destruction of prostate tissue, it is not approved explicitly for the treatment of prostate cancer.

In 2017, Golan et al conducted a systematic review to evaluate partial gland treatment of prostate cancer using high-intensity focused ultrasound in the primary and salvage settings. A total of 13 studies that enrolled 543 patients were included. Median follow-up ranged from 6 months to 10.6 years. Rates of posttreatment erectile dysfunction and urinary incontinence ranged from 0% to 48% and 0 to 50% respectively, with definitions varying by study. Overall, there were 254 reported complications. Marked heterogeneity between studies limited the ability to pool results regarding outcomes. 14% of patients subsequently received further oncologic treatment. Researchers concluded that early evidence suggests that partial gland ablation may be a safe treatment option for men with localized disease. However, longer term data is needed to evaluate oncologic efficacy and functional outcomes and will aid in identifying the optimal candidates for therapy.

In 2017, Luo et al compared the therapeutic effects of radiofrequency ablation and other ablative techniques on hepatocellular carcinomas (HCC). Databases were searched to identify literature on complete tumor ablation (CTA), overall survival (OS), local tumor recurrence (LTR), and complications of RFA in the treatment of HCC, compared with those of microwave ablation (MWA), percutaneous ethanol injection (PEI), PEI plus RFA, cryoablation (CRA), laser ablation (LSA), and high-intensity focused ultrasound. Randomized controlled trials and high-quality cohort studies were included in the assessment. Compared with RFA, identical effects were found in MWA and CRA groups. Fewer complications were observed in PEI and LSA groups. PEI plus RFA appeared more effective, with a higher rate of complications. The small amount of evidence on high-intensity focused ultrasound ablation for hepatocellular carcinomas did not allow for meta-analysis. The authors noted that in general, additional well-designed randomized controlled trials (RCTs) are needed to support study results.

In 2014, Li et al conducted a systematic review to evaluate the safety and efficacy of high-intensity focused ultrasound combined with other physical therapies for the treatment of pancreatic cancer. A total of 23 studies including 19 randomized controlled trials and four clinical controlled trials were included. Of which 14 studies reported the safety. The results of meta‐analyses showed that: the survival rate at 6 months and 12 months, overall efficacy, and clinical benefit rate in high‐intensity focused ultrasound plus radiation and chemotherapy group were significantly higher than those in groups treated with three‐dimensional conformal radiation therapy, gemcitabine, gemcitabine plus cisplatin, and gemcitabine plus 5‐fluorouracil. The authors state that the evidence suggests that the efficacy of HIFU for pancreatic cancer may be superior to other therapies, but with poor quality. They conclude that a standard and unified criterion for the diagnosis and outcome measures of pancreatic cancer is needed, and the quality of study design and implementation must be improved to achieve higher quality of evidence for proper clinical application.

While ultrasound-guided high-intensity focused ultrasound ablation is primarily used for the treatment of cancer, it is also being investigated for the treatment of a variety of other conditions. In 2016, Bai et al evaluated the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of placenta accreta after vaginal delivery. 12 patients diagnosed with placenta accreta following vaginal delivery with stable vital signs received HIFU treatment. The average postpartum hospital stay was 6.8 days, and the HIFU treatment did not appear to increase the risk of infection or hemorrhage. The authors concluded that HIFU may be a safe and effective non-invasive method for placenta accreta treatment. However, there were several limitations to this study. First, this study had a very small sample size. In addition, no comparison was made with placenta accreta patients treated by conservative means other than HIFU; such comparisons are necessary to validate the use of HIFU. This study was also retrospective in design, with a relatively short follow-up period. Additional studies are needed to better evaluate the use of HIFU for treatment of placenta accreta.

In 2017, Hung-Hin Lang et al evaluated the safety and efficacy of ultrasonography (US)-guided high-intensity focused ultrasound (HIFU) ablation as a treatment for medically refractory Grave’s disease (GD). Thirty patients underwent ablation of the entire right and left thyroid lobes, with areas near the tracheal-esophageal groove and common carotid artery left unablated. The technical success rate was 96.7%. After 12 months, eight patients experienced relapse. One patient experienced vocal cord palsy, while two patients experienced Horner syndrome. No changes in gland volume, antithyroid autoantibody levels, and ophthalmic parameters were found at 12-month follow-up. The researchers concluded that ultrasound guided HIFU of the thyroid may be a safe and effective treatment option for patients with persistent or relapsed Grave’s Disease. However, they note significant limitations, stating that further study is essential before it can become a conventional treatment for this indication.

APPROVED BY GOVERNING BODIES

In 2017, the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO) published guidelines on clinically localized prostate cancer. This guideline stated that, based on expert opinion, clinicians should inform both low and intermediate-risk prostate cancer patients considering focal therapy or high intensity focused ultrasound (HIFU) that these interventions are not standard care options because comparative outcome evidence is lacking. In addition, the guideline states that cryosurgery, focal therapy, and HIFU treatments are not recommended for men with high-risk localized prostate cancer outside of a clinical trial. Lastly, the guideline states that clinicians should inform localized prostate cancer patients considering HIFU that even though HIFU is approved by the FDA for the destruction of prostate tissue, it is not approved explicitly for the treatment of prostate cancer.

In 2022, the American Urological Association, in collaboration with the American Society for Radiation Oncology (ASTRO) with additional representation from the American Society of Clinical Oncology (ASCO), and Society of Urologic Oncology (SUO) published updated guidelines on the management of clinically localized prostate cancer. The guidelines included the following recommendation on focal treatments:

• "Clinicians should inform patients with intermediate-risk prostate cancer considering whole gland or focal ablation that there are a lack of high-quality data comparing ablation outcomes to radiation therapy, surgery, and active surveillance. (Expert Opinion)"
• "Clinicians should not recommend whole gland or focal ablation for patients with high-risk prostate cancer outside of a clinical trial. (Expert Opinion)".

In 2021, the National Cancer Institute (NCI) updated its information on prostate cancer treatments. The NCI indicated that cryoablation, photodynamic therapy, and HIFU were new treatment options currently being studied in national trials. The NCI offered no recommendation for or against these treatments.

In 2024, the National Comprehensive Cancer Network® (NCCN), updated its prostate cancer clinical practice guidelines, noting that many 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 other therapies. Cryotherapy or other local therapies are not recommended as routine primary therapy for localized prostate cancer due to lack of long-term data comparing these treatments to radiation or radical prostatectomy. At this time, the panel recommends only cryosurgery and high-intensity focused ultrasound (HIFU; category 2B) as local therapy options for RT recurrence in the absence of metastatic disease.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Covered if covered by the Participating Home Plan

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT Codes

REFERENCES

1. Bai Y, Luo X, Li Q, et al. High-intensity focused ultrasound treatment of placenta accreta after vaginal delivery: a preliminary study. Ultrasound Obstet Gynecol. 2016;47(4):492-498. doi:10.1002/uog.14867.

2. Eastham JA, Boorjian SA, Kirkby E. Clinically Localized Prostate Cancer: AUA/ASTRO Guideline. J Urol. 2022;208(3):505-507. doi:10.1097/JU.0000000000002854.

3. Golan R, Bernstein AN, McClure TD, et al. Partial Gland Treatment of Prostate Cancer Using High-Intensity Focused Ultrasound in the Primary and Salvage Settings: A Systematic Review. J Urol. 2017;198(5):1000-1009. doi:10.1016/j.juro.2017.03.137.

4. Lang BH, Woo YC, Wong IY, Chiu KW. Single-Session High-Intensity Focused Ultrasound Treatment for Persistent or Relapsed Grave’s Disease: Preliminary Experience in a Prospective Study. Radiology. 2017;285(3):1011-1022. doi:10.1148/radiol.2017162776.

5. Li CC, Wang YQ, Li YP, Li XL. High-intensity focused ultrasound for treatment of pancreatic cancer: a systematic review. J Evid Based Med. 2014;7(4):270-281. doi:10.1111/jebm.12128.

6. Luo W, Zhang Y, He G, et al. Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis. World J Surg Oncol. 2017;15(1):126. Published 2017 Jul 10. doi:10.1186/s12957-017-1196-2.

7. National Cancer Institute. Prostate Cancer Treatment (PDQ)Patient Version: Treatment Option Overview. 2021. www.cancer.gov/types/prostate/patient/prostate-treatment-pdq#link/_142.

8. National Comprehensive Cancer Network® (NCCN), Inc. Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 4.2024, - May 17, 2024.

9. Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options. J Urol. 2018;199(3):683-690. doi:10.1016/j.juro.2017.11.095.

10. UpToDate. Cryotherapy and Other Ablative Techniques for the Initial Treatment of Prostate Cancer. Updated September 13, 2018.

POLICY HISTORY

Reviewed and posted July 1, 2021.

January 2022: Annual review completed. No change to policy intent.

January 2023: Annual review completed. No change to policy intent.

January 2024: Annual review completed. No change to policy intent.

August 2024: Updates include Key points added and References added.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent, therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.