There will be “routine application” and “broader acceptance” of minimally invasive focal therapies for early-stage prostate cancer within the next 5 years in the United States, predict a trio of clinicians in a new essay published online July 28 in JAMA Surgery.
They maintain that focal therapy (FT) offers a “middle ground” between two extremes: treating the whole gland with radical prostatectomy or radiotherapy, and not treating immediately via active surveillance or watchful waiting.
Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.
The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.
“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.
But payees are already making changes, even without such data, they add.
For example, the American Medical Association announced in January a new code for high-intensity focal ultrasound (HIFU): this approach now has a Current Procedural Terminology (CPT) code from the US Centers for Medicare & Medicaid Services
Medscape Medical News reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.
“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”
The problem with focal therapy — regardless of energy modality — remains patient selection and accurate ablation zone definition, he added.
Notably, UCSF has launched a new HIFU program — and Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
While Waiting for CHRONOS, Select Wisely
The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minnesota, in an explanatory article. “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.”
However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.
Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Lebastchi and colleagues write in their essay.
They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”
Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
What Is That Evidence?
In the essay, Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: this compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease, and uniformly showed better posttreatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).
However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.
Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinder acceptance [of focal therapy] in the urology community,” the essay authors comment.
Meanwhile, careful patient selection is very important, they say.
The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.
A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.
UCSF’s Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas but we’re not there yet,” he says.
To date, some patients have been managed poorly, Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”
Some of those unfortunate results may have arisen from the US Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.
Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech.
JAMA Surg. Published online July 28, 2021. Surgical Innovation
Nick Mulcahy is an award-winning senior journalist for Medscape, focusing on oncology, and can be reached at [email protected] and on Twitter: @MulcahyNick
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