Focal therapy of just the index or primary lesion


A newly published paper in European Urology has provided us with data from one of the earliest, well-documented series of patients undergoing focal therapy of the index lesion from what is known to have been multifocal prostate cancer.o

Ahmed et al. report data from a cohort of 56 patients, most of whom had been initially diagnosed with intermediate-risk prostate cancer, and all of whom were treated with high-intensity focused ultrasound (HIFU) targeted exclusively to the index or primary lesion with the highest Gleason score.

Follow-up on this series of patients is short at this stage (at just 12 months), and the authors make no claims about the long-term outcomes for these patients. Their paper is intended to address the initial side effects and complications of treatment, and the full text of the paper is available on line.

Here is the core data from this study:

  • The average age of the patients was 63.9 ± 5.8 years.
  • The patients’ average (median) PSA level was 7.4 ng/ml.
  • 47 patients had intermediate-risk prostate cancer.
  • 7 patients had low-risk prostate cancer.
  • 2 patients had high-risk prostate cancer.
  • All patients were evaluated by multiparametric MRI and prostate biopsies.
  • At baseline, 40/56 patients (71.4 percent) were leak-free, pad-free, and had erections sufficient for penetration.
  • At 12 months post-treatment,
    • 33/56 patients (58.9 percent) remained leak-free, pad-free and had erections sufficient for penetration
    • 48/52 patients (92.3 percent) remained leak-free.
    • 46/50 patients (92.0 percent) remained pad-free.
    • 30/39 patients (76.9 percent) still had erections sufficient for intercourse.
    • The patients’ median PSA nadir decreased to 2.4 ng/ml.
    • 42/52 patients (80.8 percent) had no histological evidence of clinically significant cancer.
    • 48/56 patients (85.7 percent) had no measurable prostate cancer (based on biopsies and/or mpMRIs).
    • 2/56 patients (3.6 percent) had clinically significant disease in untreated areas not detected at baseline.

Ahmed et al. conclude that:

Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinically significant cancer. Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy.

A detailed editorial commentary on this study by Polascik et al. is also available on line. They state that the study by Ahmed and his colleagues

presents a real-world picture of patients treated with focal therapy who likely require treatment for their cancer and not a low-risk population that arguably does not require intervention.

They also point out that while focal therapy is not going to be appropriate for every patient, it will probably be appropriate for some, and they praise the authors for initiating what they clearly see as an important and “ground breaking” clinical initiative, the results of which need to be evaluated with “open minds”.

The “New” Prostate Cancer InfoLink also sees this as being an important study. Data from larger studies of this type — in which patients are followed for significantly longer time frames — will help us to appreciate the true clinical effectiveness of focal therapy (using HIFU and other forms of focal therapy). They will also help us to understand whether the ablation of the index lesion is sufficient in the long-term management of men known to have additional, lower-risk tumors at the time of diagnosis and treatment.

8 Responses

  1. This represents the future for many new diagnosed mpMRI-detected patients and reflects my clinical experience over the past 6-7 years.

    Bravo!

  2. I think it’s worth pointing out that 19% (10/52) still had clinically significant cancer after the first treatment, 2 of whom were successfully (as of 1 year) retreated. It’s also worth noting that 43% had some residual cancer detected at the end of the year — not surprising because they were only treating the “index lesion.” So it seems that most men getting this treatment are on lifelong active surveillance but without the ability to use PSA at all as an early detection tool (we have no idea what a PSA recurrence looks like) — a lifetime of targeted biopsies.

    The other thing that surprised me is that the sexual and urinary side effects of treatment were low, but not remarkably low. Erections were preserved in 77% and pad-free continence was preserved in 92% at 12 months; 5.4% had to have TURP for urethral strictures at the bladder neck.

    By comparison, Katz reports for SBRT at 7 years that erections were preserved among 71%, there was no urinary incontinence, and 1.7% had a TURP for stricture or laser coagulation for bleeding. In that study, 11% of intermediate-risk men had biochemical recurrence, but only a quarter of those were local failures requiring retreatment.

    Since only 2 men in the Ahmed study were re-treated so far, we don’t know what side effects are attached to retreatment.

    So based on this small study of limited duration, I don’t see compelling evidence for this technique.

  3. I don’t believe HIFU is the best method for focal therapy.

    I believe doctors using laser are getting better cancer control rates and less side effects, compared to HIFU.

    And they ablate all visible tumors and suspicious areas, not just the index lesion.

  4. Numerous prior studies of HIFU have looked as good as any other therapy during the first several years of follow-up before turning sharply downward around the fourth and fifth years. In view of that context, how can we give any weight to follow-up of just 12 months post treatment?

    The description of this study (NCT00988130) at http://www.clinicaltrials.gov gives no indication that further follow-up is planned. It’s hard to get enthusiastic about this study.

  5. Dear Doug:

    You may be right … but there are no published data yet, which is getting a little distressing.

  6. Dear Jim:

    Rightly or wrongly, this study was not intended to address efficacy. The authors are very clear about that. On the other hand, this is one of very, very few published studies on focal therapy … and the only one in which patients appear to have been followed closely for any length of time in a prospective manner with a specific and predetermined objective.

    The reason for any “enthusiasm” about such a study is because it has actually been done and published … and should therefore stimulate further publications.

  7. Dear Sitemaster,

    I fully agree with your statements, but there is a reason to emphasize the efficacy side of HIFU treatment when quality of life and side effects are discussed.

    The serious concern I have is that patients and their loved ones need to also and primarily think hard about HIFU efficacy statistics – a concern you have also expressed, which are not good except for one of the Uchida series in Japan which did have results I found impressive end encouraging but based on specific advances in technology. We are already hearing fresh interest in HIFU in our Us Too education and support group (past two monthly meetings.

    It is worrisome that people seeking information will encounter what I found on the site “HIFU International” (http://www.internationalhifu.com) today. As of today, December 10, 2015, the first reference from the results topic at this site [Sonablate] was a 2009 paper on the first UK HIFU series by HU Ahmed (the lead author in the subject paper on focal HIFU above) and colleagues with a 92% success rate (“successfully treated) for HIFU treatment of the whole gland.

    From the paper, efficacy results were stated as “Overall, there was no evidence of disease (PSA <0.5 microg ml(-1) or negative biopsy if nadir not achieved) after one HIFU session in 92.4% (159 out of 172) of patients.” This was with follow-up of just one year after treatment for 172 men. Moreover, as near as I can see after reviewing papers by Dr. Ahmed and separately by Dr. Emberton, there has not been a single follow-up to this 2009 study regarding efficacy! The absence of reasonably anticipated and appropriate follow-up always sounds an alarm bell for me. (There have been a lot of other interesting publications on HIFU by the team, but no efficacy follow-up.) The seriousness of the absence of efficacy follow-up in the six ensuing years up to the present is spotlighted by the research context: all other series, except the one Uchida series published in 2014, with follow-up to at least the fourth year document a discouraging sharp fall-off in success (basically meaning no recurrence evidence) around the fourth and fifth year, with some decline in the third year, making those success statistics for the first and second year temporary indeed.

    I'm wondering if anyone has a reassuring explanation why the London team (Ahmed, Emberton and colleagues) has not followed up their 2009 paper.

    Also, in the context of other research, it is shameful that HIFU International is misleading potential patients by still highlighting one year results from a 2009 study!

    All this said, I am glad you are bringing the subject study to the attention of the prostate cancer community, and I appreciate that you are doing serious education on HIFU such as the recent HIFU webinar with Dr. Scionti.

    PS: Of course the subject study is about focal HIFU rather than whole gland HIFU. However, as efficacy success with focal HIFU is more challenging than with whole gland treatment, it seems that success should first be demonstrated with whole gland treatment -– sort of like learning to walk before you try to run.

  8. Dear Jim:

    Two key issues related to the effectiveness and safety of HIFU are going to be patient selection and the skill and experience of the treating team. As yet, there are almost no really well-documented and published data on the effectiveness and safety of HIFU (whole gland or focal) from any experienced center at all. The one possible exception being the Uchida data from 2014 we have both referred to in the past.

    I now believe that everyone needs to be cautious about making decisions about the use of HIFU based on data from any patients treated before about 2010 (when most equipment wasn’t as good as it needed to be and few centers had relevant experience). I always take what is promoted on commercial sites with a large pinch of slat in any case. Such data are inevitably promotional in nature since they have to have met criteria approved by the company for commercial use.

    My suspicion is that further data on the longer-term outcomes of some of the patients from the Ahmed/Emberton team will be forthcoming over time, but they may not be interested in publishing such data until they have meaningful 5-year survival data (at a minimum).

    With regard to your comment about only studying whole-gland therapy prior to studying focal therapy … I disagree. It seems perfectly reasonable to me that one could study both at the same time. That issue comes back to appropriate selection of patients for the differing types of treatment.

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