Focal HIFU in treatment of (largely) intermediate-risk prostate cancer

In addition to the French data previously referred to on this site, data from another, much larger cohort of men treated with focal, high-intensity focused ultrasound (focal HIFU) are also to be presented at the upcoming annual meeting of the American Urological Association.

This paper by Guillaumier et al. (abstract no. MP18-08) comes from the Ahmed/Emberton group in the UK and encompasses > 600 men, most of whom were diagnosed with intermediate-risk, localized prostate cancer and all treated at one of eight institutions in the UK between 2004 and 2015.

The median follow-up on this cohort of patients is still relatively short, at 56 months (about 4½ years), and so — as we shall see below — the survival data are very good, as one might expect. What Guillaumier et al. have focused on in this paper is the process they used to select patients for treatment and the shorter-term outcomes, side effects, and complications associated with treatment in this large patient cohort.

It is worth noting that this group of clinicians in the UK has now treated > 2,000 men with either whole-gland or focal HIFU since 2003, so their experience base is now considerable. Here are the data on patient selection and management:

  • As part of their diagnostic work-up, all potentially eligible patients received
    • A multiparametic MRI and
    • A transperineal mapping biopsy and/or
    • An MRI-targeted biopsy and
    • Standard bone and CT scans to exclude any risk for metastatic disease (if the patients were intermediate- or high-risk)
  • Focal HIFU therapy took one of three forms, depending on the size and location(s) of the cancer:
    • Hemiablation (treatment of one of the two lobes of the prostate)
    • Single quadrant ablation (treatment of half of one or other of the two lobes of the prostate)
    • Index lesion ablation only (in carefully selected men with Gleason 6 disease and a maximum core length of 5 mm)
  • All patients were followed using PSA testing, repeat prostate biopsies, and MRI scans as necessary.

And here are the outcomes data at a median follow-up of 56 months:

  • 625 patients were enrolled and treated.
    • 80/625 men (12.8 percent) had low-risk disease.
    • 491/625 men (81.0 percent) had intermediate-risk disease,
    • 39/625 men (6.2 percent) had high-risk disease.
    • 15/625 men (2.4 percent) seem to have not been assigned to a specific risk category.
  • Average (median) PSA level at diagnosis was 7.1 ng/ml.
  • Average (median) nadir PSA level post-treatment was 1.7 ng/ml at 4.5 months of follow-up.
  • With respect to follow-up treatments required and given
    • 173/625 men (27.7 percent) were given additional treatment of any type.
    • 122/625 men (19.5 percent) were given additional focal HIFU.
    • 44/625 men (7.0 percent) were given radical, whole gland treatment (mostly radiation therapy).
    • 7/625 men (1.1 percent) required androgen deprivation therapy (ADT) alone.
  • 8/625 men died during the follow-up period, but none died of prostate cancer.
  • Estimated survival rates at 5 years of follow-up were
    • 97 percent for metastasis-free survival
    • 99 percent for overall survival
  • Follow-up, postoperative biopsies were carried out on 222/625 patients (35.5 percent).
  • Among those 222 patients
    • 34/222 men (15.3 percent) had a positive biopsy result.
    • 18/222 men (8.1 percent) had in-field disease recurrence.
    • 5/222 men (2.2 percent) had out-of-field de novo disease or progression.
    • 11/222 men (5.0 percent) had in-field recurrence and out-of-field de novo disease or progression.
  • Baseline data on urinary continence were recorded for 429/625 patients (68.6 percent)
  • Among those 429 patients
    • At 1 to 2 years after focal HIFU
      • 305/314 men (97.1 percent) were pad-free.
      • 209/251 men (83.3 percent) were pad-free, leak-free continent.
      • We have no data from the other 125 patients.
    • At 2 to 3 years after focal HIFU
      • 241/247 men (97.6 percent) were pad-free.
      • 156/195 men (80.0 percent) were pad-free, leak-free continent.
      • There are no data from the other 182 patients.
  • Baseline data on erectile function were recorded of 425/625 patients (68.0 percent).
  • Among those 425 patients
    • At 1 to 2 years after focal HIFU
      • 138/165 men (84 percent) had maintained baseline erectile function.
      • There are no data from the other 260 patients.
    • At 2 to 3 years after focal HIFU
      • 87/101 men (86.1 percent) had maintained baseline erectile function.
      • There are no data from the other 324 patients.
  • With respect to other, major complications and side effects
    • 2 men developed a recto-urethral fistula, of whom
      • 1 healed with urinary diversion alone.
      • 1 required operative reconstruction.

Guillaumier et al. conclude that focal HIFU, in this cohort of patients, at least,

has acceptable rates of cancer control with a low genitourinary side-effect profile in the medium-term and across a number of centers. It is a low cost, ambulatory and repeatable procedure that is minimally invasive.

What is of real value in this study (in the view of The “New” Prostate Cancer InfoLink) is the following:

  • The fact that the Ahmed/Emberton group have again provided us with high-quality data from a large, consistently managed cohort of men
  • The very high proportion of men in this study who had intermediate-risk disease at diagnosis (> 80 percent)
  • The very low proportion of men in this trial who had low-risk disease at diagnosis (< 15 percent), and we know that this clinical team encourages low-risk patients to opt for active surveillance as a first-line management option if they believe this to be appropriate
  • The relatively low percentage of men (< 30 percent) who needed additional treatment of any type at a median follow-up of 56 months
  • The even lower percentage of men (< 10 percent) who needed any treatment other than focal HIFU at a median follow-up of 56 months

There are a couple of key questions that can be raised as a result of these data:

  • How many of the men who were high-risk at initial diagnosis needed which types of follow-up treatment?
  • What would these data look like if one excluded the men diagnosed with high-risk disease?

If a high proportion of the men who needed additional treatment — and particularly treatment other than focal HIFU — came from the high-risk group in this cohort, one is tempted to conclude that (in experienced hands) focal HIFU is beginning to look like a very promising first-line treatment option for men diagnosed with intermediate-risk prostate cancer. But on the other hand, why do these data look so similar to the French data previously discussed? In that series of patients, some 74 percent of men were clearly low risk, with Gleason scores of 6 or less, a PSA less than 10, and clinical stage T12c or T2a. Does this tell us that using focal HIFU (or any type of HIFU) in low-risk patients is — yet again — likely to be over-treatment, because the risk for side effects outweighs any real oncologic benefit?

4 Responses

  1. I must be a glass half-full kind of person because I am not seeing the positive side of HIFU. Biopsy data is only provided on a third of the cohort of which 20% were positive and 17% were not leak-free, pad-free continent. Despite treating men since 2004, we have only 5-year survival data, which does mean very much for this disease. Granted this was focal therapy but that does not mean the bar for assessing success should be lowered. Why aren’t more people concerned about this short-term result before making such glowing praise. Given the thousands of men treated around the world, overall survival has rarely been reported for either focal or complete therapy. Why?

  2. Dear Gerry:

    The fact that the manufacturers of HIFU equipment did a thoroughly lousy job of compiling long-term outcomes data shouldn’t detract from the fact that Emberton and Ahmed and co. ARE now providing those data and they should be considered with the same care that you would give to any other new form of therapy with 5-year outcomes data.

    I would point out that in the UK you can ONLY get HIFU within the context of this registry study, and frankly my own view is that that should be the case in the USA too … but that isn’t going to happen because the FDA has approved HIFU.

  3. I’m glad they are studying this closely. There are so many unanswered questions: does oncological control differ between favorable and unfavorable intermediate risk? Do side effects increase with the size and location of treated areas (e.g., large areas near the urethra or bladder)? Is it possible to lower the high retreatment rate with better patient selection? What happens to the side effect profile with re-treatment — is that where the fistulas occurred? What happens over time to the cancer that is not ablated? I confess that I have doubts that the “index lesion hypothesis” is as universally applicable as Emberton seems to believe. I look forward to their full peer-reviewed report.

    I think it’s great that they are investigating this and hope this will add to our armamentarium. However, to keep this in perspective, it is worth pointing out that LASTING cancer control has been achieved in intermediate-risk patients with the same favorable side effect profile. At 5 years in in a study of intermediate-risk patients treated with HDR brachy monotherapy:

    • 94% were free of biochemical recurrence — much better than HIFU
    • Maintenance of potency was equally high (82%)
    • Only 2.5% used a pad occasionally or less than once a week among those without prior TURP, stroke or tremor. This is also similar to HIFU.

  4. There are still no long-term studies of HIFU in prostate cancer, and most of the patients in trials would have been on active surveillance (with zero side effects), if they weren’t given HIFU.

    More damning of all is that not one study has directly compared (and matched subjects) with either radiotherapy or surgery. Not one.

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