Half of prostate focal therapy falls outside guidelines, study finds

Just over half of the American men who received focal therapy for prostate cancer fell outside the narrow patient group that treatment guidelines support, according to an analysis of nearly 1.2 million cases published in the journal JAMA on Aug. 13.

The analysis came from the University of Pittsburgh and drew on the National Cancer Database, which collects records from hospitals accredited by the Commission on Cancer. It covered 1,179,384 men aged 50 and older diagnosed with nonmetastatic prostate cancer between 2010 and 2023, of whom 15,672, or 1.3 percent, received focal therapy. Its senior author is Quoc-Dien Trinh, the university's chair of urology.

One label, many methods

Focal therapy is not a single procedure. It targets only the part of the prostate that holds cancer, destroying it with heat, cold or laser energy and leaving the rest of the gland intact. The tools include high-intensity focused ultrasound, the technology Sonablate sells, along with freezing and laser techniques, and providers argue that different methods carry different cure rates and different side effects, so judging the field as one thing obscures how far they diverge.

It's focal therapy no matter how you did it. But the reality is all those tools do have varying outcomes, varying side effects, varying cure rates

Peretsman made that criticism to STAT News about most registries, saying they combine every method under one heading regardless of how the tumor was destroyed. Sonablate, which sells the ultrasound device, launched a registry of its own in May.

The appeal of the approach is plain. Set against removing the whole prostate or irradiating it, focal therapy aims to spare urinary and sexual function, and it is usually delivered in one session. In a statement issued by the university, Trinh said that for appropriately selected intermediate-risk patients the treatment "aims to preserve quality of life while treating the cancer," but he and his co-authors found that its use has spread faster than the evidence behind it.

The tradeoffs in side effects

Surgery has long been the standard for anything more than low-grade disease, and its costs are well documented. Nearly all men are incontinent immediately after a prostatectomy, the removal of the prostate gland, and while most regain bladder control within a year, a minority never do. In a federal study of men treated in the mid-1990s, about 8 percent were still incontinent 18 months on and 60 percent were impotent; both figures predate nerve-sparing and robotic technique.

Radiation carries fewer long-term urinary side effects than surgery, but it can still cause temporary incontinence and erectile dysfunction, and it is likelier than surgery to cause bowel problems. Courses run from four or five weeks down to as few as five sessions, depending on the schedule.

Focal therapy providers point to a British registry study of 3,477 patients published in European Urology in July. It estimated that 0.13 percent had died of prostate cancer within ten years, a rate the authors put on par with survival after surgery or radiation. The estimate rests on two deaths, and on an intention-to-treat basis a third of the men needed further local treatment within ten years.

What the British study did not do was assign patients at random to focal therapy or to standard treatment. That distinction sits at the center of the disagreement, because without a randomized comparison it is hard to know whether the men who fared well would have fared as well under surgery, or were simply the patients most likely to do well under any treatment.

Still called experimental

The American Urological Association still calls focal therapy investigational, for low- and intermediate-risk disease alike. Its guidelines list active surveillance, radiation and radical prostatectomy as the options for favorable intermediate-risk cancer; ablation is not among them. Doctors who offer the treatment argue it should be tracked through prospective registries, and some of them say those registries are flawed because they treat every method as equivalent.

Guidelines the association issued jointly with the American Society for Radiation Oncology, amended this year, say the same thing. Men with low- and intermediate-risk disease should be told that whole-gland or focal ablation is investigational and that high-quality data comparing it with standard treatments are lacking, and the guidelines recommend against ablation for high-risk disease outside a clinical trial. Both statements are graded expert opinion rather than evidence.

An editorial published alongside the Pittsburgh analysis put the skeptics' case sharply. Titled "The Emperor's New Clothes - The Discipline of Evidence," it was written by Spyridon Basourakos and Jonathan Shoag of University Hospitals Cleveland Medical Center and Daniel Spratt of University Hospitals Seidman Cancer Center, and argues that unproven treatments should not be offered outside clinical trials.

No completed long-term randomized trial has directly compared focal therapy with surgery or radiation. Several are running, among them the British CHRONOS trial.

Where the evidence stops

The Pittsburgh researchers did not argue that focal therapy should be abandoned; their concern was that just over half of recipients sat outside the intermediate-risk group where the guidelines contemplate its investigational use.

The case each side makes

Proponents read the British survival figures as evidence that carefully chosen patients can avoid the incontinence and erectile dysfunction that follow radical treatment. For them, holding the approach to a decade of randomized follow-up before it is offered widely denies men a gentler option that already exists and performs well in the data available so far.

Skeptics answer that satisfaction scores and short-term function say little about whether a cancer has been cured, and that a treatment tracked only through registries that mix methods will never yield the clean comparison the field needs. They want the randomized trials the guidelines themselves say are missing.

Between those positions sits the specific gap the study measured. Among the men treated outside the guideline group, the low-risk cases may have been treated when active surveillance, monitoring the cancer rather than acting on it, would have sufficed, while the high- and very-high-risk cases may not have been treated aggressively enough to control a cancer more likely to spread.

What happens next

For now, the treatment keeps moving from specialized centers into routine practice faster than the trials can catch up, the pattern the analysis set out to document. Device makers and academic centers are building registries, Sonablate's among them, to gather the outcomes the guidelines demand, though a registry that pools different methods is not the randomized trial the editorial called for.

The analysis pressed a broader question that reaches past prostate cancer, whether a new treatment is reaching the patients most likely to benefit from it. The finding that about half of recipients fell outside the endorsed group is why that question has not gone quiet.

The study carries limits of its own. It counted how many men received focal therapy and in which risk category, drawing only on hospitals accredited by the Commission on Cancer and leaving out care given elsewhere. It tracked who was treated and how well the choice matched the guidelines, not whether any of the men were ultimately helped or harmed.

The stakes behind the numbers are old ones. For most solid tumors, surgeons try to preserve as much of the diseased organ as they can, but prostate cancer has been treated as all or nothing, the whole gland removed or irradiated except in the mildest cases.

Focal therapy is the attempt to end that exception, and whether it earns a permanent place will depend on trials that do not yet exist. Until they report, the guidelines will keep the treatment inside studies while its supporters keep offering it, and the divide the JAMA analysis documented will stay where it is.