Summary Men with grade 2 or 3 prostate cancer are often not considered eligible for active surveillance; Some patients with grade 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focal ultrasound therapy can safely reduce the treatment burden for patients with localized grade 2 or 3 intermediate-risk prostate cancer. Methods In this multicenter, single-arm, phase 2b study conducted at eight healthcare centers in the US, we enrolled men aged 50 years or older with unilateral, MRI-visible, primary, intermediate-risk prostate adenocarcinoma . , previously untreated (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumor classification ≤T2) confirmed on combined biopsy (combining targeted and systematic MRI biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60 to 70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using resonance thermometry. real-time magnetic for intraoperative control. The co-primary outcomes were oncologic outcomes (absence of grade 2 or higher cancer in the treated area at the combined 6-month and 24-month biopsy; when 24-month biopsy data were not available and grade 2 or higher cancer had occurred). 2 or higher in the treated area at 6 months, biopsy results at 6 months were included in the final analysis) and safety (adverse events up to 24 months) in all patients included in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting. Results Between May 4, 2017 and December 21, 2018, we screened 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. The median age was 63 years (IQR 58-67) and the median prostate-specific antigen concentration was 5.7 ng/mL (IQR 4.2-7.5). Most cancers were in the grade 2 group (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79–94]) of 89 men had no evidence of grade 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths. Interpretation Biopsy results at 24 months show that MRI-guided focused ultrasound therapy is safe and effectively treats grade 2 or 3 prostate cancer. These results support focal therapy for selected patients and its use in comparative trials to determine whether a tissue-sparing approach is effective in delaying or eliminating the need for long-term radical whole-gland treatment. |
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In recent years, a new treatment strategy known as focal therapy (partial gland ablation) has emerged for prostate cancer that is considered “intermediate risk,” mostly small tumors confined to one area of the prostate. . At Memorial Sloan Kettering Cancer Center (MSK), researchers have been working closely with an advanced focal therapy approach known as high-intensity focused ultrasound (HIFU), guided by magnetic resonance imaging (MRI).
Now, a landmark clinical trial has shown that this less invasive method works well for many patients.
The Phase 2 trial, led by MSK urologic cancer surgeon Behfar Ehdaie, looked at a particular type of HIFU treatment, also called MR-guided focused ultrasound (MRgFUS), in men with intermediate-risk cancer. The new approach effectively controlled the disease in patients and greatly reduced the adverse side effects of the treatment. This suggests that many men with intermediate-risk prostate cancer can avoid surgery, chemotherapy, and radiation.
“We believe this new treatment strategy will improve the lives of many prostate cancer patients,” says Dr. Ehdaie. "To draw a parallel with the way breast cancer treatment changed 30 years ago, you could think of focal therapy as a ’male lumpectomy.’ Instead of removing all tissue from a breast or prostate, we’ve learned that “It is safe and effective to treat specific areas and greatly reduce the burden on patients.”
The results of the clinical trial, published in The Lancet Oncology, represent an important step towards the new HIFU approach becoming part of the widespread treatment of breast cancer. prostate.
When cancer is confined to the prostate gland, the main treatment options have traditionally included active surveillance (close surveillance), surgery, and radiation. But men who needed surgery or radiation often had lingering side effects, such as urinary and sexual problems, that could reduce quality of life.
“Advances in prostate cancer over the past two decades have been led by successes that have benefited all patients, and now focal therapy provides another exciting area that can move the needle in prostate cancer management,” he says. Dr. Ehdaie.
How does HIFU work for prostate cancer?
MR-guided focused ultrasound (MRgFUS) is an outpatient treatment that lasts about two hours. Patients under anesthesia are placed in an MRI machine that covers the lower half of the body. After the machine takes an image of the prostate, doctors outline the treatment area and emit focused ultrasound waves, guided by MRI. Ultrasound waves come from different directions and cross paths to attack and kill cancer by heating cells above 70°C (158°F).
“While you’re taking images, you’re also getting temperature information to make sure the right spots are being treated,” says Dr. Ehdaie. “The patient wakes up from anesthesia and goes home. There are no incisions or wounds on the body to heal. “We have shown that the procedure is safe for patients and they can return to their normal activities immediately.”
Patient Success Story with HIFU Treatment for Prostate Cancer
John Brannan is one of the success stories. In 2016, when he was 65 years old, his prostate-specific antigen (PSA) began to rise sharply. Although prostate cancer is largely not hereditary, he was alarmed because his father, his uncle and two of his cousins died from the disease. A Boston doctor suggested surgery to remove the cancer as soon as possible. But that night at dinner, John spoke with two of his wife’s friends who had undergone prostate cancer surgery and discussed some of the side effects that had lingered. A friend knew about the clinical trial and put John in touch with MSK medical oncologist Howard Scher, who referred him to Dr. Ehdaie.
John was eager to sign up. “In addition to the personal reasons for wanting this treatment, I also hoped to help the next generation who could benefit,” he says. “I have seen the effect this disease can have on my own family.”
John says the process was easy. Dr. Ehdaie scheduled the MRgFUS treatment at Memorial Hospital’s Image Guided Interventions Center in September 2016. John left several hours later and returned to the hotel with his wife and had dinner. “Everything went back to normal immediately,” he says. “No cuts, no stitches, no lying in a hospital bed for days or weeks. I used a catheter for the first 24 hours and was a little tired, but that was it. The treatment was actually less painful than the biopsies they did.”
Making HIFU available to more patients
Dr. Ehdaie says the use of MRgFUS for intermediate-risk cancers was made possible by two important developments over the past 15 years. First, experts accepted the use of active surveillance for low-grade tumors. The second advance was new imaging technology that allowed MRI to be incorporated into ultrasound treatment.
In the phase 2,101 clinical trial, men received the new MRgFUS treatment and then underwent a biopsy six months and 24 months later. No intermediate- or high-risk cancer remained in the treated area in 88% of patients.
“Probably the most important thing was the lack of side effects,” says Dr. Ehdaie. “No one in the study reported urinary incontinence or experienced bowel problems. Most men were able to achieve erections.”
Based on this data, the FDA in December 2021 granted approval for the technology, called Exablate Prostate, to treat prostate tissue. The FDA also approved an investigator-initiated trial designed by Dr. Ehdaie and surgeon Peter Scardino to compare MRgFUS focal therapy with active surveillance and demonstrate clinical benefit for patients with prostate cancer.
’A new chance at life’
More than five years later, John is still doing well and has avoided surgery and radiation treatment. He has annual follow-up checkups and periodic surveillance biopsies at MSK to make sure the disease has not returned. Now 70, he lives in Florida with his wife and remains active buying and renovating properties.
Since his treatment, he has received calls from friends and acquaintances across the country asking how they can get it too. MSK will offer this novel treatment to selected men and hopes to launch the Phase 3 clinical trial soon as well.
“I feel like I’ve been given a new lease on life, so I’m trying to make the most of it,” John says. “It’s a phenomenal use of technology, and I think it’s absolutely going to take off around the world.”
