Aug. 21, 2021
Derek J. Lomas, M.D., Pharm.D., a urologist and specialist in focal therapy for prostate cancer at Mayo Clinic in Rochester, Minnesota, discusses the addition of high-intensity focused ultrasound (HIFU) to the prostate cancer focal treatment armamentarium.
Provide a little history: How did HIFU progress to a treatment for primary prostate cancer?
The first HIFU prostate cancer clinical trials, completed in the mid-1990s, showed that HIFU could ablate prostate tissue successfully. This finding led to additional studies, and HIFU ultimately entered clinical practice around the world during the following decade.
Initially, HIFU was used to perform whole-gland ablations for prostate cancer. While this application was successful, there was increasing interest in limiting prostate cancer treatment-related side effects by restricting the amount of the prostate that was treated. This treatment approach is termed focal therapy.
The goal of focal therapy is to treat only the area with the most aggressive tumor while leaving the rest of the prostate and its surrounding structures alone. This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.
The prostate tumor that is targeted is referred to as the index lesion. In prostates with more than one tumor, this is generally the largest tumor with the highest grade. In these cases, it is believed that the index lesion drives the behavior of the prostate cancer and that treating it alone with focal therapy may lead to good overall cancer control with fewer side effects.
What type of patient is particularly well suited for HIFU?
The ideal candidate for focal therapy typically has intermediate-risk prostate cancer located in only one area of the prostate. This location is determined by prostate magnetic resonance imaging (MRI) and targeted prostate biopsy. My ideal candidate for focal HIFU has a lesion in the posterior or lateral portion of the prostate, a small- to moderate-sized prostate, and no major prostate calcifications or large cysts.
What are the major contraindications to HIFU?
There are a few limitations to HIFU. The first is prostate volume or size. HIFU treatment is delivered through a probe in the rectum, and the treatment can only reach so far away from the rectum. If patients have large prostates and anterior tumors, the energy may not reach anterior enough to provide effective treatment and negative margins. Sometimes tumors in larger prostates can still be treated if the target tumor is in the posterior part of the prostate.
The next limitation is calcifications in the prostate, which are problematic for a couple of reasons. First, the ultrasound energy cannot travel through dense material such as calcifications, so any areas of the prostate behind these may be undertreated. Next, these calcifications can reflect the energy, which could potentially lead to unwanted heat being transferred back to the rectum.
Other potential contraindications include inflammatory bowel disease of the rectum, prior significant rectal surgery, inability to insert the transrectal probe into the rectum, urethral stricture or active infection.
How do you counsel patients who receive HIFU? What is the typical side effect and complication profile? What is the typical recovery?
Overall the focal HIFU procedure is very well tolerated. HIFU is done as an outpatient procedure with a same-day discharge. A Foley catheter is placed during the procedure and is usually left in place for 5 to 7 days following the procedure to allow post-treatment swelling of the prostate to subside.
Once the catheter is removed, most patients do have some temporary obstructive and irritative urinary signs and symptoms including urinary urgency, frequency, slower stream and dysuria. We can manage the signs and symptoms with medications, and patients typically get better within a few weeks.
Rates of new urinary incontinence and erectile dysfunction developing are generally lower than those with prostate removal surgery but are dependent on the location within the prostate being treated. Other side effects that can occur include urinary retention, urinary infection, ejaculatory dysfunction, urethral stricture and rectal fistula (rare).
Most men are able to resume general activities in 1 to 2 days, including regular short walks. More intense physical activity can be resumed once the catheter is removed. There are no incisions to care for or stitches to remove.
Briefly, what are the logistics of the delivery of HIFU?
The HIFU procedure is done while the patient is under general anesthesia. Once the patient is completely anesthetized, a special ultrasound probe is placed in the rectum. There are no incisions or even any needles used. This ultrasound probe is used to both image the prostate and deliver the treatment. Once the initial positioning and planning steps are complete, treatment is delivered.
Each HIFU treatment lasts just a few seconds and destroys an area of tissue that is about the size of a grain of rice. An ablation zone is created by delivering multiple treatments to cover a predefined area of the prostate based on imaging and biopsy results. During the treatment, the surgeon is given real-time imaging as well as treatment parameters including temperature readings and calculated tissue changes to assess the quality and success of ablation. The procedure length depends on the size of the area to be ablated but in general takes approximately two hours.
How do you see HIFU playing a role in prostate cancer treatment over the next 10 years?
I see focal therapy in general becoming an option for more men in the next 10 years as more data supporting its use emerge and more providers become trained in the techniques. HIFU will definitely continue to be one of the main technologies used in prostate cancer focal therapy. There will continue to be ongoing research on other ablation technologies as well. To have a well-rounded focal therapy program, we must have multiple ablation technologies and techniques available to allow for focal therapy to be offered to a wide range of patients. There is still a role for radical prostatectomy and radiation therapy, and certainly they remain the standard of care at this point, but I think focal therapy should at least be part of the treatment discussion in men who are appropriate candidates and seeking a less invasive treatment option.
High-intensity focused ultrasound (HIFU) ablation of the prostate showed “adequate” short-term prostate cancer control, indicating the minimally-invasive procedure is an acceptable alternative to immediate surgery or radiation, according to new research from USC Urology, Keck Medicine of USC.1
Among 100 patients with prostate cancer who received HIFU, 91% were able to avoid radical treatment for at least 2 years, according to the retrospective analysis, which was published in the Journal of Urology. Also, nearly three-fourths (73%) of patients did not experience treatment failure, and there was a 100% continence preservation rate.
“This positive data empowers urologists to use focal HIFU ablation to effectively address prostate cancer without the intrinsic side effects of radical treatments,” first author Andre Abreu, MD, urologic surgeon with Keck Medicine and an assistant professor of clinical urology and radiology at the Keck School of Medicine of USC, stated in a press release.2 “We hope this study encourages prostate cancer patients to talk to their doctor about all potential treatment options to ensure that they receive a personalized care plan that addresses their individual needs.”
Between December 2015 and December 2019, 100 consecutive men received hemigland HIFU using either Ablatherm (EDAP TMS) or Sonablate 500 (SonaCare). The median patient age was 65 years (interquartile range [IQR], 59-70) and the median PSA at baseline was 5.9 ng/ml (IQR, 4.5-7.2). The median prostate volume at baseline was 34 cc (IQR, 27-46). Per MRI, 71% of patients had a PI-RIAD score ≥3. Eighty-five percent of patients had stage T1c disease, 12% had stage T2a disease, and the remaining 3% had stage T2b or T2c disease. Per NCCN definition, disease risk status included very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%), and high (5%).
Treatment failure was the primary end point of the study. The trial design defined treatment failure as follow-up biopsy showing Grade Group 2 or higher disease, metastases, systemic therapy, radical treatment, or prostate cancer–specific mortality. Other outcomes measured included 90-day complications, International Prostate Symptom Score (I-PSS), and International Index of Erectile Function (IIEF).
The median follow-up period was 20 months. At 2 years, 91% and 73% of patients remained free from radical treatment and treatment failure, respectively. Also at 2 years, 90% of patients did not need repeat focal HIFU, and 76% of patients successfully avoided grade group 2 or greater recurrence.The only baseline disease characteristic associated with Grade Group 2 or greater recurrence was having bilateral prostate cancer at diagnosis (P = .03).
All 100 patients maintained continence (zero pad). The median I-PSS scores before and after hemigland HIFU were 9 versus 6 (P = .005), respectively. The median before and after treatment IIEF-5 scores were 22 versus 21 (P = .99), respectively.
Overall, there were 13 minor complications after HIFU, and no major complications. The minor complications were grade 1 neuropraxia (n = 1), grade 1 urinary retention/insufficient voiding (n = 7), and grade 2 urinary tract infection (n = 5). There were no cases of rectal fistula and no patients died.
“USC Urology is dedicated to refining cancer care through collaboration and innovation,” senior author Inderbir S. Gill, MD, founding and executive director of USC Urology and senior author of the study, stated in a press release.2 “Throughout screening, diagnosis and treatment, it is important to balance accuracy and efficacy. Our physicians will continue working toward better methods to personalize that balance for every prostate cancer patient,” added Gill, who is also Distinguished Professor and chair of the Catherine and Joseph Aresty Department of Urology, Shirley and Donald Skinner Chair in Urologic Cancer Surgery and associate dean for clinical innovation at the Keck School.
In an accompanying editorial published in the Journal of Urology, Massimo Valerio, department of surgery and anaesthesiology, Urology Unit, Lausanne University Hospital, Lausanne, Switzerland, wrote, “Since FDA clearance, this is the first US series reporting on [partial gland ablation (PGA)] using HIFU. Although this study has the inherent limitations of a retrospective analysis, the authors deserve credit for having quickly and safely adopted this technology in their program. This might serve as an example for novel centers implementing PGA.”3
1. Abreu A, Peretsman S, Iwata A, et al. High intensity focused ultrasound hemigland ablation for prostate cancer: initial outcomes of a United States series. J Urol. 2020;204;741-747. doi: 10.1097/JU.0000000000001126
2. Innovative, minimally invasive treatment can help maintain prostate cancer patients’ quality of life. Published online September 8, 2020. https://bit.ly/3jUhfAf. Accessed September 8, 2020.
3. Valerio M. Editorial comment. Re: High intensity focused ultrasound hemigland ablation for prostate cancer: initial outcomes of a United States series. J Urol. 2020;204;747. doi: 10.1097/JU.0000000000001126