Focal Therapy for Prostate Cancer, Instead of 'Sledgehammer' Approach

Pam Harrison

March 09, 2015

VIENNA — One of the pioneers of focal therapy for prostate cancer, which has been described as a "male lumpectomy," says that cancer control is good in the short and immediate term, and the majority of men retain potency and continence.

"I think the way forward is an image-guided prostate pathway, where we all do imaging and biopsies and then treat patients on the basis of what we see, not use some sledgehammer approach where we apply surgery or radiotherapy [to the whole prostate gland], regardless of what we find," said Hashim Ahmed, MD, PhD, senior lecturer at University College London in the United Kingdom.

Dr Ahmed presented data here at the European Congress of Radiology 2015 on more than 500 men with prostate cancer who have been treated by his group with high-intensity focused ultrasound (HIFU), either while participating in trials or in clinical practice and followed up in a registry.

At a median follow-up of 3 years (range, 1 to 8 years), prostate-cancer-specific survival is still 100%, he reported.

"Redo" rates range from 13.6% in clinical trials to 18.6% in the registry, he noted, but only 0.5% of either group has so far required salvage therapy.

Metastases-free survival rates are over 99% at the same follow-up point in both groups of men.

"There will be more failures as we follow these men up," Dr Ahmed told delegates. "But so far, this is very acceptable and encouraging. We've found that functional outcomes are great — and this in a treatment modality that you can repeat."

Dr Ahmed and colleagues have been using HIFU as a focal treatment for prostate cancer in their clinic in the United Kingdom since 2009, but there has been great resistance to this approach in the United States, where removal of the whole prostate gland remains the standard of care. Over the past year, American experts have called HIFU an experimental therapy and have said that the idea of focal therapy for prostate cancer is based on a 'questionable' scientific paradigm, and a US Food and Drug Administration advisory panel voted against recommending approval of a HIFU device.

However, urologists are moving closer to the concept of focal therapy for prostate cancer, at least in Europe, said Arnauld Villers, MD, from the urology service at Hôpital Claude Huriez in Lille, France.

It clearly reduces genitourinary morbidity significantly more than radical prostatectomy, he told Medscape Medical News.

"The first concept was to send patients to active surveillance for a single small cancer, which is now routinely done. The second concept was to treat the index lesion with focal therapy modalities," he said. "But you can mix the two together," he explained. "You can treat one lobe with the index lesion and not treat the other lobe with a single very low micro-foci of cancer."

Dr Villers noted that having very good tools, including MRI, helps physicians be more confident when following patients for the transformation of an indolent cancer to more aggressive disease.

"Mixing these two concepts is being validated now, but it took many years for us to convince the scientific community that we were going in the right direction," Dr Villers acknowledged.

"I'm totally in line with this approach, and I favor HIFU as well, because it is easy for urologists to do, it's very effective, and we can offer it as a same-day surgery," he said.

Turning Away From Whole-Gland Treatment

What prompted Dr Ahmed to turn away from the whole-gland radical prostatectomy approach? He explained that part of his motivation was his distrust in the "blind" transrectal ultrasound (TRUS) biopsy.

"The TRUS biopsy is terrible," he said. "It detects indolent disease that does not harm the man, it misses cancers, and it misclassifies cancers in a significant number of men."

"And then that error is confounded downstream by subjecting men to whole-gland treatment, which carries harm and very little benefit," he explained.

In fact, when Dr Ahmed first started the focal therapy program at University College London about 8 years ago, "we were all doing radical prostatectomy and it was quite clear that the surgery carried significant morbidity — on average, 20% incontinence, 50% erectile dysfunction — and this in the best of centers," he told Medscape Medical News.

Over the same period of time, data were coming out showing that surgical treatment was benefiting men in terms of survival only marginally, if at all.

"In fact, the vast majority of men were being treated unnecessarily," Dr Ahmed said. "So something needed to change. We needed a better strategy for diagnosis"

That strategy turned out to be a form of prebiopsy multiparametric (mp)MRI. Before doing a biopsy, mpMRI gives clinicians the location of a suspected cancer, and diagnosis is done with the help of an MRI-guided biopsy, Dr Ahmed explained. He reported that he does virtually all biopsies transperitoneally because he feels the TRUS route carries an unacceptably high risk for sepsis.

As with almost all other solid organ tumors, mpMRI of the prostate allows clinicians to localize the suspicious lesion in the gland first, and then, using MRI-guided biopsy and focal treatment, diagnose and target only the lesion, which limits collateral damage to tissues surrounding the lesion and reduces adverse treatment-related effects.

Evaluation of early MRI data from University College London and elsewhere showed that MRI is acceptably, although "not 100%," accurate, Dr Ahmed reported. "We're still only getting about 60% accuracy with the TRUS biopsy; with MRI, we have about an 80% to 90% accuracy rate."

One of the main advantages of using MRI is that clinicians have a location for the index lesion, and they can target that lesion alone using an ablative technique such as HIFU and preserve the rest of the gland, he explained.

However, the first obstacle to this approach is how to address the unavoidable fact that much of prostate cancer is multifocal.

And not all prostate cancers are significant. As it turns out, MRI predictably picks up the most clinically significant cancers, and tends to underdiagnose those that are low grade and low risk, said Dr Ahmed.

"Increasingly, we know that low-risk, low-volume prostate cancers may not behave like cancer at all, and if some lesions can be classified as low risk, they should be left untreated," he added. "The minute you accept that, the potential for focal therapy becomes very real."

Less Collateral Damage

Even from their earliest experience with focal HIFU, it was clear that most men regained their potency and most were continent after the procedure, Dr Ahmed said.

It was also clear that they were getting good cancer control with treatment of the index lesion, despite the fact that low-risk, low-volume disease might well remain in the prostate.

In fact, Dr Ahmed and colleagues demonstrated that ablation of the index lesion most likely to cause disease progression is effective and leaves erectile and urinary function pretty much intact in a recent study (Eur Urol. Published online February 11, 2015).

After HIFU treatment, pad-free continence rates in the 56 men treated with HIFU was preserved in 92% of men overall, and erections sufficient for intercourse were preserved in more than 75% of the men.

At 12-month follow-up, 80% of the men had no histologic sign of clinically significant cancer, and approximately 85% had no measurable disease on either biopsy or mpMRI.

Although follow-up in that study was short, the findings suggest that it is possible to treat the largest and highest-grade tumor in men who have more than one known prostate tumor and achieve acceptable rates of early cancer control with a low risk for genitourinary adverse effects, the investigators conclude.

"HIFU is not the only focal therapy; there's cryotherapy, irreversible electroporation, which electrocutes cells, and even injectable toxins," Dr Ahmed said.

"And we can now use MRI to guide focal therapy follow-up because the ability of MRI to rule out significant disease after focal therapy is very high," he said.

Dr Ahmed reports receiving grants from a number of companies, including Sonacare, Sophiris, Trod Medical, and Angiodynamics, to run clinical trials. Dr Villers has disclosed no relevant financial relationships.

European Congress of Radiology (ECR) 2015: Abstract A-330. Presented March 6, 2015.

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