How many current, PSA-detected, localized prostate cancers are really appropriate for focal therapy?

It is well understood that current Western screening and diagnostic processes commonly identify patients with low volume, low Gleason grade prostate cancer tumors (e.g., a single biopsy core with < 10 percent of the core  positive for cancer of Gleason score 3 + 3 = 6). What is not so clear, as yet, is how best to identify patients who may be suitable candidates for focal therapy from among all those low-risk men who present with such intitial clinical findings at diagnosis.

Catto et al. have recently published data based on an analysis of data from 525 men, all enrolled in the ProtecT trial in the United Kingdom, and who underwent a radical prostatectomy as their first-line treatment. These men were all diagnosed as part of a population-detected set of men in a very highly structured clinical trial protocol. For additional information about the ProtecT trial, please click here.

The results of the analysis by Catto et al. showed the following:

  • Radical prostatectomy specimens were available from 525 men, for whom complete biopsy and related diagnostic data (PSA level, Gleason score, clinical stage, number of positive biopsy cores, etc.) were also available.
  • Solitary tumors were identified in prostatectomy specimens from 100/525 men (19 percent).
  • Of the 425 men with multiple tumors visible in the post-surgical prostatectomy specimen, 73 (17 percent) had a solitary, significant focus of tumor.
  • At best, therefore, 173/525 men (33 percent) actually had prostate cancer that was arguably appropriate for focal therapy.
  • Most of these 173 men had small, well-differentiated tumors that appeared to be pathologically insignificant.
  • 130/525 men (25 percent) would have been considered potentially suitable for focal therapy based on current diagnostic criteria.
  • Of these 130 men
    • 34 men (26 percent)  had the significance of their cancer underestimated.
    • > 50 percent were (arguably) over-treated.
    • Only 24 men (18 percent) were actually found to have a significant, solitary lesion.

Catto et al. conclude that, “Focal therapy appears inappropriate for the majority of men presenting with PSA-detected, localized prostate cancer.”

That conclusion may well be valid, but the data suggest that about one-third of men currently being diagnosed with clearly localized prostate cancer (at least in the UK) actually do have a single, significant, solitary lesion. The question then becomes whether men with the potential for such a finding, and therefore the potential for appropriate focal therapy, should be considered as candidates for an extended re-biopsy as part of the process of deciding whether active surveillance, focal therapy, or some other treatment is the most appropriate option for their management.

12 Responses

  1. This post describes exactly where I [age 69] am at now and is most helpful.

    By treating every man diagnosed with protate cancer [probably 25% of men over 55], are we subjecting them to unnecessarily aggressive treatment[s]? On the other side of the [“P.C. coin”] is that there is almost always a dominant focus of cancer [the site it starts off at and then spreads from over time].

    I await with significant interest the result of clinical trials using robot-guided focal laser therapy being conducted at Princess Margaret Hospital’s Prostate Centre in Toronto. [See “Quality of life in the balance” in Our Voice, Volume 16, No. 2.]

    Thanks, Al H.

  2. We must continue to educate men with prostate cancer about the potential of focal therapy. Too of them are being over-treated and diminishing their quality of life unnecessarily.

    The key to determining the appropriateness of a man for focal therapy is the 3D mapping biopsy. It gives the patient the information he needs to make the decision as the appropriate treatment.

  3. If a man were diagnosed as indicated — a single biopsy core with < 10 percent of the core positive for cancer of Gleason score 3 + 3 = 6 — it would probably be more prudent to follow a closely monitored active surveillance protocol. This prevents "over-treatment;" makes more sure that a "focal" treatment does not miss cancer cells that are located elsewhere in the gland than in the area of focal treatment and not yet developed to identification on imaging or missed in biopsy; and permits a longer period of "quality of life" by avoiding the invasiveness of surgery or radiation until diagnostics during active surveillance indicate that such invasive treatment has become necessary. That being said, more often than not, men learning of the presence of "cancer" want it "out," despite it being in the earliest stages of development; unfortunately, too many urologists and radiation oncologists encourage that desire.

  4. Dear James and Chuck:

    Two critical factors in decisions about the appropriate treatment of men with low-risk prostate cancer are the the reasonable life expectancy of the patient and his will/ability to live with the potential risk of progression on active surveillance.

    We already have sufficient data (from the Scandinavian and PIVOT studies) to suggest that there is no meaningful survival benefit from any form of surgery (focal or whole gland) for most (but not all) men of 65 and older with low-risk prostate cancer. By contrast, for younger men, it is reasonable to accept that some will just want such tumors removed because they don’t want to live with the risks associated with progression while on active surveillance; others (like Terry Herbert) would happily embrace those risks. These are very personal decisions.

    What men do need, however, is accurate data and personalized risk assessment from their doctors that will allow them to make a fully informed decision. A mapping biopsy is certainly a component of that data, but mapping biopsies come with their own risks, and the number of biopsy cores to be taken needs to be carefully assessed based on the volume of the prostate and biopsy guidance technology available, as well as available data from the initial diagnostic biopsy. I would not want to be seeing vast numbers of men getting 40- or 50-core mapping biopsies as a component of their decision to have active surveillance or focal therapy. Men who want to know whether active surveillance would be a reasonable treatment option for them do need a repeat, standardized biopsy within 12 months of their initial diagnosis. Men who want to know if focal therapy is possible for them do need a mapping biopsy, but it is not yet entirely clear what the appropriate number of biopsy cores is for such a biopsy (relative to the prostate volume) — especially if it is being done under some types of MRI guidance.

  5. Here is a link to a press release summarizing a recent research study that analyzed the value of the 3D mapping biopsy in helping both clinicians and patients make treatment decisions. As you can see the decisions were away from radical treatment.

    It is all about being patient centered; giving the patient enough information so he can make the decisions about what kind of treatment he wants.

  6. I was baffled by the Catto et al paper.

    Take this quote: “Criteria used to select patients for focal prostatic ablation underestimated the cancer’s significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions” for a start.

    Whose criteria are they using to select patients?

    ‘…men presumed eligible for focal therapy..’ What on earth does that mean? Their presumption for eligibility? Some international criteria?

    Just meaningless in my opinion.

    I asked a leading focal therapy researcher for their opinion on the paper and their succinct reply was: ‘…a very poor paper as only TRUS biopsy was used to select men. Of historical interest only’.

  7. Richard:

    Like all retrospective reviews, that is what it is, a retrospective review. However, since we have almost no prospective data from which to draw conclusions, while your “tame” “leading focal therapy researcher” is correct in his evaluation of the paper as being of historic interest (in the long term), we have almost no published, prospective data at present on the basis of which a newly diagnosed patient can make decisions. People therefore have to try to base estimates on what is available.

    All that the Catto et al. paper is saying is that their data help to give some perspective on what proportions of men being diagnosed in the UK in recent years may be eligible for focal therapy. Because they have the pathology data, they can tell you the exact correlations between the numbers of men who might have been considered for focal therapy and the numbers of men who actually had only one clinically significant focus of cancer. Those data are accurate. Since I haven’t seen the full paper, I can’t give you details on exactly which criteria they used to assess eligibility, but I am sure it is given in the full text.

    You can only rarely make assessments of the detailed value of a paper on the basis of the abstract, and you shouldn’t try to read too much into any retrospective analysis of this type … ever! It’s not a “poor” paper. It is only what it claims to be. Most published data are not the results of randomized, double-blind trials! Indeed, I am not aware that anyone is running any randomized trial of focal therapy anyway. We are going to get a bunch of case series (again), and all that they will tell us is that some surgeons can get better data than others, so I am not holding out much promise for a paper that can really tell us the magnitude of any quality of life benefit from focal therapy (e.g., with HIFU) to whole gland therapy (also with HIFU) — assuming comparable efficacy — in a cohort of low-risk patients.

  8. Thanks, Mike. As neither of us have seen the paper, I’ll request a copy tomorrow; having the criteria will help us both to comment accurately.

  9. Richard: That may be true, but I honestly don’t think there is much more to be said about this paper, which was exactly why I never tried to get the entire text in the beginning. The key “learning” from this paper at the present time is basically that unless you are relatively young or have an unusually long life expectancy of 90+, the chances that focal therapy will be any better as a form of treatment than active surveillance for low-risk prostate cancer are probably low for most men over 65. And about half the men who get diagnosed with prostate cancer of any grade are still 65 or older.

  10. Are Catto et al. assuming focal therapy as a single intervention or as multiple interventions delivered across time to manage lesions as they might or might not progress from insignificant to requiring treatment?

    The intensity of commitment by the conventional treatment community to destroy the quality of life for as many men as they can for as much of the lives of those men as they possibly can is not to be understated.

    The very conservative 25% estimate, of course, of this very conservative application of focal therapy represents thousands and thousands and thousands of real men with real lives who would be spared years to decades of life partially to wholly impotent and incontinent.

  11. Tracy:

    Focal therapy to data has usually meant a one-time intervention. In time it might be possible to do sequential focal therapy, but I do not know of many people who have even considered trying such an approach. Even with focal therapy (using today’s technology) one is still treating a pretty significant volume of the prostate as opposed to a few cubic millimeters.

  12. Tracy has hit the nail on the head. If targeted focal therapy (TFT) can maintain the quality of life of 25% or more of men who are now undergoing radical treatment then TFT needs added to our standard treatment modalities.

    As for repeat treatments, this already being considered by those that are providing this treatment. The Duke Medical Center Focal Therapy web site talks about making prostate cancer a chronic disease.

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