A pathological “take” on the potential role of focal therapy

Various forms of focal therapy are now being used by some physicians to treat selected patients with well-identified, usually relatively small, “dominant” or “index” tumors that are confined to highly defined areas of the prostate. The idea is to avoid “whole gland” removal or ablation of the prostate and thereby leave the patient with a higher probability of erectile/sexual function and better continence post-treatment — while simultaneously eliminating any cancer that has the potential to metastasize and thus lead to the patient’s death.

Now it has to be said that the effectiveness of focal therapy has been much disputed on the basis of two major concerns:

  1. That prostate cancer is commonly a multifocal disease and that while a physician may be able to effectively treat a single well-identified index lesion, there may be other lesions that remain undetected and untreated and can progress over time.
  2. That standard biopsy techniques have, historically, been well understood to under-grade localized prostate cancer and fail to sample what may be the most important lesion in the prostate of a patient with prostate cancer.

A new article by Gordetsky et al., to be published in Urology (the Gold journal) has offered us a review of the potential role or roles of focal therapy from the perspective not of the treating clinician (whose views are often going to be affected by his or her personal attitude to how well specific types of focal therapy may be carried out) but rather from the pathological perspective of clinicians who specialize in the examination of prostate tissues post-biopsy and post-surgery.

This pathological perspective is interesting because it basically asks us to look at focal therapy not necessarily as a curative form of treatment but rather as a form of treatment that would subsequently allow a patient to be managed by active surveillance. To give a specific example of what we mean by this (which is not an example used by the authors), imagine the following scenario:

A patient of 64 years of age is diagnosed (after a standard 12-core biopsy) with apparently localized but “favorable” intermediate-risk prostate cancer — clinical stage T1c disease, a PSA level of 3.7 ng/ml, with two small positive biopsy cores (< 5 mm of cancer in each core; one of Gleason 3 + 3 = 6 and the other of Gleason 3 + 4 = 7). Both positive cores are in a single quadrant of the prostate, making focal therapy of some type a theoretical possibility. The patient is still highly sexually active and has a strong desire to ensure that he remains that way if at all possible. What is he to do?

What Gordetsky et al. initially argue is the following:

  • A standard 12-core biopsy is insufficient to be able to inform either the patient or his physician that he really does have prostate cancer confined to a single quadrant of the prostate.
  • Even if the patient was to have a repeat, saturation or mapping biopsy, it is still possible (on the basis of available data) that a clinically significant focus of prostate cancer might be missed.

However, they go on to argue that

  • The availability of high-quality. multiparametric MRI scanning has “changed the game” with respect to the probability of being able to identify areas of clinically significant prostate cancer.
  • That such a patient, if given a high-quality, multiparametric MRI (that is conducted and interpreted by a suitably qualified uro-radiologist) can give a patient and his clinician a high sense of confidence (but not absolute certainty) about
    • Whether a repeat biopsy under MRI/TRUS fusion guidance (or in-line MRI guidance) is necessary because there are other areas of the prostate that look suspicious for prostate cancer
    • Whether, after such a repeat biopsy under MRI/TRUS fusion guidance (or in-line MRI guidance), focal therapy is still a reasonable option

However, they say this with the important reservation that focal therapy should never be considered to be “curative” at the time it is carried out. At best, such therapy is designed to eliminate a clinically significant area of cancer within the prostate that then allows the patient to be subsequently monitored over time (effectively on active surveillance), which may or may not indicate the need for further treatment later on.

In the specific case of the patient mentioned above, for example, it might be possible to effectively ablate the two areas of cancer in a single quadrant of his prostate — using, for example, focal laser ablation (FLA) or high-intensity focused ultrasound (HIFU) — and leaving the three other quadrants of his prostate untreated. The patient would then be given a repeat MRI guided or a repeat MRI/TRUS fusion biopsy perhaps a year after initial treatment to check for any presence of remaining or recurrent cancer, and if no cancer or perhaps only a small amount of Gleason 3 + 3 = 6  prostate cancer was found, the patient could then simply be monitored on active surveillance for risk of recurrence (which might or might not ever happen).

Your sitemaster considers this to be a very practical way of looking at the pros and cons of focal therapy.

We have known for a while that:

  • A man who has prostate tissue left behind after treatment for prostate cancer is always at risk that some of that tissue might be cancerous (but whether it is clinically significant prostate cancer tissue can be harder to determine).
  • Focal therapy does not allow for patients’ PSA levels to drop into the undetectable range, and so it is hard to necessarily determine, post-treatment, whether or not a man has been “cured” of his prostate cancer if he is treated in this way.
  • Focal therapy is associated with a higher probability than whole gland therapy for maintenance of and/or recovery of good quality continence and erectile/sexual function.

By applying the pathological perspective offered by Gordetsky et al. and combining it with other factors that may be influential for a particular patient in considering the pros and cons of focal therapy. it would appear that we are getting closer to being able to help individual patients determine whether any one of the currently available forms of focal therapy may be “right for them”.

The “New” Prostate Cancer InfoLink would continue to emphasize, however, that focal therapy is probably never going to be possible for men with any amount of Gleason pattern 4 disease in both lobes of the prostate. We would also note that the decision to consider focal therapy is always one that each individual patient must consider carefully — ideally in close consultation with a physician who has considerable experience in the use of one or more of such types of therapy, and who insists on a role for multiparametric MRI scanning and MRI-guided or MRI/TRUS fusion-guided biopsy as a component of the patient evaluation process.

Other tests that may be appropriate in the decision to consider focal therapy might include one or more of the genomic/genetic tests now available that can also help to determine the aggressiveness of cancer from selected biopsy cores.

Once this paper is published, later this year, we would encourage prostate cancer support group leaders and other prostate cancer educators to obtain a copy of the full text of this paper for their files. The full text provides additional and detailed back-up for the perspective offered by the authors.

Editorial note: The “New” Prostate Cancer InfoLink thanks Dr.  Jennifer Gordetsky of the University of Alabama at Birmingham for kindly providing us with the complete text of this paper for our evaluation prior to development of the above commentary.

4 Responses

  1. As a side issue to this article, is it fair to say that the authors see a 3T mpMRI as a better approach to take after initial diagnosis than doing another biopsy?

  2. John:

    I think there is a gradually evolving consensus that after diagnosis, if any type of repeat biopsy seems like a good idea, it should really be done either after an mpMRI of some type (ideally 3 T. but it depends on the technology available), i.e., as an MRI/TRUS fusion-guided (or better still an “in bore” MRI-guided biopsy) or as a transperineal biopsy that makes it a great deal easier to sample tissue from the anterior regions of the prostate.

  3. Thanks for getting back.

    I’ve had two MRIs (3 T multiparametric) over the last 2 years since my original biopsy (Gleason 6 at diagnosis). The MRIs are clear but my consultant is pushing to do a transperineal biopsy, which I’m not keen on.

    This is the first article I’ve seen which seems to suggest that the 3 T mpMRI is a valid path to take instead of another biopsy.

  4. Dear John:

    As I said before, there is an evolving consensus about the role of mpMRI but not an absolute one. Men who have negative MRIs can and still do sometimes have progressive prostate cancer (i.e., a Gleason score of 3 + 4 = 7 or higher in your case) even when they have a negative MRI, which is why many urologists will want to do a repeat biopsy of some type within a couple of years of the initial diagnosis. Different studies to date seem to suggest that the percentage of men who have a false negative mpMRI like this might be about 5 to 15% (depending on the study).

    In the end, this is a decision that only the patient can make for himself. There is no “right or “wrong”. It all depends on the willingness of the patient to accept the risk of not having a repeat biopsy (and I can understand your reluctance to consider the transperineal biopsy, especially since this has to be done under anesthesia).

    We cannot tell you what to do in a case like this. If there is nothing visible on the MRI, then there is no point in doing an MRI/TRUS fusion biopsy since there is nothing to target. That does mean that if you were to have another biopsy the best type to have would be a transperineal biopsy — but whether that is absolutely necessary is between you and your doctor to resolve.

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