In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped.
Previously in a normal range, LaFrate’s PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions.
LaFrate had low-risk prostate cancer.
Guidelines now recommend active surveillance for patients like LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.
LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age.
LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.
At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.
LaFrate’s urologist asked him to pay $25,000 out-of-pocket to undergo the focal procedure at a clinic in the Bahamas. LaFrate refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.
That urologist was “a shyster in my opinion,” LaFrate said.
Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy.
But use of the techniques remains controversial and costly.
As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs.
No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.
Without a stamp of approval from guideline bodies and insurance companies, patients, like LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques.
“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland, Ohio.
Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.
“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Spratt said.
Evidence-based or Oversold?
Focal therapy gained a foothold in the United Kingdom well before the United States.
Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.
“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Ahmed said.
In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this ” innovative technique” predict its routine use in the next few years.
But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.
In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Ahmed said.
The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.
A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.
One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Ahmed.
In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.
Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.
A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence.
Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.
When patients see Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.
Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland, Ohio. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”
The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.
“The lack of randomized clinical trials poses a major stumbling block for the field,” said Ahmed.
Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore, Maryland. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, George said.
Focal therapy is now in the same position that active surveillance was a few years ago, according to George.
“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.
But Shoag has a different take on the trajectory of focal therapy research and care in the United States.
“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Shoag said.
William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Catalona said. But “giving these patients focal therapy is really overtreatment.”
Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Catalona explained.
Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.
George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy.
“There is concern that patients may be receiving biased information,” George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.
At the end of the day, Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?”
LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.
Following an MRI in 2022, LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”
Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for LaFrate.
LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.
“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” LaFrate said. “I just have a hunch I don’t need it at this point.”
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