Focal therapy today: upsides and downsides


While there is considerable allure to the theory behind focal therapy (and focal laser therapy or FLA in particular) as a treatment for some men with localized prostate cancer, it is worth understanding that there are good reasons to consider this allure with great caution. In stating this, we wish to be extremely clear that we are not “anti” focal therapy at all. We simply don’t, as yet, have enough data to know who it really works well for as a patient (let alone whether we can pre-define those patients with high accuracy).

A paper published by Adamczyk et al., from the Nicolaus Copernicus Hospital and University (in Bydgoszcz, Poland), lays out the problem rather nicely.

The authors conducted a retrospective analysis of data from a cohort of 720 men who were suspected of being at risk for prostate cancer (based on PSA and other data). All these men underwent a prostate biopsy, and 324 of them were found to have prostate cancer. Here are the consequent data from the research team’s analysis:

  • 81/324 men found to have prostate cancer underwent a radical prostatectomy.
  • Of these 81 men,
    • 25 percent (i.e., 20/81 patients) could, prior to their surgery, have been qualified for focal therapy, based on the available pre-surgical data, because it was reasonable to think that they might have unifocal prostate cancer.
    • However, based on the pathological, post-surgical data,
      • 10 percent (i.e., 8/81 patients) were found to have pT2a disease.
      • 5 percent (i.e., 4/81 patients) were found to have pT2b disease.
      • 65 percent (i.e., 53/81 patients) were found to have pT2c disease.
      • 20 percent (i.e., 16/81 patients) were found to have pT3a to pT4a disease.

Adamczyk et al. then argue that:

  • Only 15 percent of the patients had truly unilateral (pT2a,b) disease.
  • Only 25 percent of the patients had truly unifocal disease (a single focus of cancer in the entire prostate)
  • Focal therapy is really only appropriate in men with unilateral or unifocal disease.
  • Using currently available technology, proper T-staging of the cancer and the quantity of cancerous tissue within the prostate can not be assessed with high accuracy prior to treatment (of any type).

They go on to conclude that:

  • Focal therapy should not be used in patients with high-risk disease, even when their likely pathological stage is ≤ pT2b.
  • Active surveillance is a valid and appropriate management strategy for most other patients with low-risk disease.
  • Focal therapy is a potentially “interesting therapeutic proposition for a small group of patients” whose pathological stage is likely to be pT2a (with the reservation that it is not possible to select such patients with accuracy based on current imaging technology).

We lay out this argument not to either justify it or to deny it … only to note that it is a “reasonable” point of view. For patients who are interested in focal therapy as a treatment option, it is important to appreciate the points being made by Adamczyk et al. (and others who would agree with them).

If patients with any form of high-risk disease go to have focal therapy because they have pre-determined that (a) it will cure their prostate cancer and (b) it will leave them with full erectile and sexual function and minimal risk for other complications, then a significant percentage of those patients is likely to be disappointed (in many cases because they will have progressive disease later on).

Furthermore, if patients go to have focal therapy because they have low-risk, unifocal disease (implying that they may well be an excellent candidates for active surveillance), then they are having treatment when they may not need it at all, in which case they are risking side effects of treatment that they may never have need to have and with no evidence that the treatment was ever necessary.

The potential of focal therapy is very high indeed — if (a) we can work out which men really benefit from this with a high degree of probability; (b) we can work out which men are much less likely to benefit; and (c) we can develop a cadre of clinicians who can execute the necessary therapeutic techniques with a high degree of reproducible skill and a suitable experience base.

There are reasons why, in Europe, focal therapy for localized prostate cancer is currently defined as “experimental”. Here in the USA, some would define it as “experimental” (e.g., insurance companies and other payers) and some would defined it as “investigational” (its advocates and some others). At present we have only a very small number of clinicians with any significant experience at all; a serious lack of published outcomes data (after even 1 or 2 years of follow-up, let alone 5 or 10); and no good prospective data on the correlation between pre-treatment findings and post-treatment outcomes.

It is worth noting that there are also two “pro” and “con” articles on the role of focal therapy in the management of low- and very low-risk prostate cancer in the most recent issue of Oncology:

In writing the current commentary, readers need to appreciate that The “New” Prostate Cancer InfoLink absolutely does not wish to discourage any man interested in the potential of focal therapy from considering, evaluating, or actually having such therapy. Indeed, we actually encourage some men to consider this as a treatment option (if they can get their health plan to pay for it, or if they can afford to pay for it themselves). On the other hand, we do wish to be very clear that all such men need to evaluate opportunities for focal therapy “with eyes wide open” as to the possible downsides as well as the potential upsides.

16 Responses

  1. Can you please tell me why a person would not want to try focal laser ablation first even with the possibility of cancer returning or advancing? If you cut out the prostate there are no alternatives left to preserve function. If you are smart enough to investigate FLA and can afford it then it makes sense to start with that since it does not preclude a person from pursuing more conventional therapies. And of course presuming you are proactive in managing active surveillance post-FLA treatment.

  2. Lisa:

    If there is a significant probability of any of the following, then focal laser ablation is not going to be a very wise form of treatment because there will be a high likelihood of continuing risk for micrometastasis — even immediately after the FLA: a clinical stage of T2c or higher, any significant amount of Gleason 4 + 4 = 8 or higher, or a PSA > 15 ng/ml. Thus, by the time the patient discovers that the FLA hasn’t worked, he may well have lost the chance of any form of curative treatment.

  3. If you have advanced stage prostate cancer then most likely you would not qualify for FLA anyway so that is a moot point I would think. It seems that it is ideal for intermediate stage cancer. As in my husband’s case (Gleason 3 + 4 = 7).

  4. Dear Lisa:

    I would tend to agree that FLA is potentially a very good option for men with low-volume, intermediate-risk prostate cancer that appears to be confined to no more than half of one lobe of the prostate, and who have a PSA level of 10 ng/ml or less. If I was in your husband’s situation, I would certainly want to consider FLA, and I would want to have a 3-T MRI and (if it seemed appropriate based on what could be seen on the MRI) a repeat biopsy prior to any decision that I was a good candidate.

    It is completely true that FLA is not a good idea for men with “advanced” prostate cancer. However, “advanced” disease is customarily defined by the suspicion of or actual presence of positive lymph nodes or actual metastatic disease or a PSA level of > 20 ng/ml. The problem comes (as described in the original commentary above) in that many men who appear to have low or intermediate risk at the time of diagnosis turn out, later on, to have been at significantly higher risk. The trick that needs to be solved is finding a standardizable way to define the patients who are truly good and truly poor candidates for FLA, so that a patient and his doctors can have a really sensible conversation about the risks up front, and come to a mutually acceptable decision. If we could do that, then it would be much easier to conduct really good clinical trials to prove the effectiveness of FLA in highly defined groups of patients.

  5. We have had a 3-T mpMRI and are proceeding with FLA early next month. We surely hope to be a statistic that proves FLA is viable for men with the same risk as my husband. We all look forward to the day when it is a treatment you do not have to scour the Internet for but is widely available for all whom qualify and is covered by insurance and is presented as an option by all urologists. I agree that it will be wonderful also to be able to be screened more easily than having to wait 60 days to have an MRI because your urologist did a random biopsy on you. Let’s hope it is in the near future!

  6. In the era of mpMRI, can’t we treat the visible cancer with FLA, and then use mpMRI to find any new cancers which may appear?

    If you miss a small amount of high-grade cancer, is that really a big deal? If it grows, it should show up on a subsequent MRI, in time to treat.

    IMO, most old men have some small amount of high-grade prostate cancer.

    FLA debulks some amount of cancer, which radiation does not, and is much less disruptive than prostatectomy, leading to less release of cancer into the lymph system.

  7. Dear Doug:

    (1) With regard to the question of whether “If you miss a small amount of high-grade cancer, is that really a big deal”, the answer is yes, it may be. For example, it would be a big deal if you had FLA at 45 years of age and then your next sign of any real clinical problem was a sudden rise in your PSA and subsequent evidence of incurable micrometastasis. There is no guarantee — even in an era of 3-T mpMRI — that we can consistently identify recurrent disease after FLA early enough to always prevent such occurrences. This is a risk that any patient who elects to undcergo FLA nees to be fully aware of.

    (2) Your opinion that “most old men” (which may need better definition) “have some small amount of high-grade prostate cancer” has not been borne out by any autopsy data that I am aware of.

    (3) I know of no evidence to support your comments about tumor debulking and the possible release of cancer cells into the lymphatic system one way or another, but what I can tell you is that it is theoretically perfectly possible that this could occur when FLA is carried out, when radiotherapy is carried out, and when any other type of localized treatment is carried out too. Whether this comes with significant risk for later metastatic disease is utterly unproven (again, one way or the other).

  8. For those who are interested, Dr. Hashim Ahmed kindly brought to my attention two videos that are accessible on line that comprise a debate between Dr. Ahmed himself (“pro” focal therapy) and Dr. Patrick Walsh (“con” focal therapy) in lectures given at a focal therapy meeting in Pasadena, CA, in August this year.

    At the end of the day, it seems to me that — based on the available data — the use of focal therapy in any individual patient is very much a matter for individual discussion between a patient and his doctors. There are opportunities and there are risks, as with every other form of treatment for localized prostate cancer. In the end, only an individual patient can make the decision whether he wants to take the possible risks to gain what may be an uncertain set of benefits. Given that situation, the critical issue is whether the patient is being given all the information he needs to make an appropriate decision that really works for him.

    The bottom line is still that we need more data to really determine which are the most appropriate patients for this form of treatment and which are definitively not. Without such data, there is much hypothetical discussion and limited sound, long-term follow-up data, most particularly for focal laser ablation therapy (as opposed to other forms of focal therapy).

  9. Here is my own experience with prostate cancer and FLA:

    I was suspected to have prostate cancer on August 19, 2014, by DRE by my GP. THis was confirmed by my urologist on August 20, 2014. On August 29, a 3-T MRI by Dr. Joe Busch in Chattanooga showed a suspected, clinically significant cancer. On October 8, a 3-T MRI-guided biopsy by Dr. Busch revealed a single focus of Gleason 3 + 3 tumor, right side mid-gland, 24 mm of tumor occupying 69% of tissue, PNI, ERG overexpression, PTEN negative. I began my due diligence on courses of treatment.

    After consulting with my urologist, Dr. Ray Pak, I decided that focal laser ablation was the best corse of action. On November 3, FLA was performed successfully by Dr. Eric Wales at UTMB: no pain, no side effects other than a couple of days of urgency to pee, no more cancer.

    I have no illusions about my prostate cancer being gone forever, but think that if this gets me 5 to 10 years down the road, then it is worth it. My radiologist felt that with ERG overexpression, PTEN negative, and PNI the stage was set for the cancer to become more aggressive. Since the cancer was located mid gland, away from nerve bundle and urethra and had not escaped the prostate capsule, this made FLA an easy choice. It also took care of my BPH by reducing my overall prostate volume.

    I am glad to speak with anyone that would like more information.

    Henry

  10. Sitemaster,

    Thank you for urging caution with focal therapy.

    There was an abstract published last week by urotoday.com which looked at post-op RP specimens from patients with T2 disease and only 15% would have been candidates for focal therapy.

    Someone posted a comment here recently that he was opting for focal therapy with high-grade disease. You did not sound thrilled to hear this, but thank you for taking a position now about focal therapy and high risk disease.

    Like you have said, the decision to try focal therapy has to be carefully weighed. I for one would definitely want to get all the information I could about the prostate cancer before deciding, including mpMRI (preferably done before the biopsy) and genetic tests on the biopsy specimen. Even with that, there could still be unknowns, as you also sald.

    The literature reviews here are so good and on target. What a tremendous public service this site is providing. Thank you again.

  11. Dear Walter George:

    The paper referred to on the UroToday web site appears to be the same paper as the one referred to in the above commentary.

  12. With standard biopsy sampling less than 1% of the prostate, small volume high grade cancer must be missed all the time. Unless there is a decent volume of cancer, it must often be missed.

    My point is that prostate cancer is not treated until a decent volume of cancer exists, and a decent volume of high grade prostate cancer will be picked up on a mpMRI.

  13. Doug:

    Unfortunately: (a) we aren’t in an “era” when mpMRI is available to the vast majority of patients, and we won’t be for a considerable period of time; (b) we aren’t in an “era” when — even if mpMRI was available to most patients — there are enough specialist uroradiologists to interpret the prostate scans with accuracy; and (c) by the time a high-grade tumor is large enough for one to be “certain” to pick it up on an mpMRI scan, it is also large enough to have started to micrometastasize.

  14. Agree with your response, but major institutions are quickly adopting AS as the treatment of choice for men with Gleason scores of 7 or less.

    To me, FLA is basically AS + debulking.

    FLA must be more effective than AS, at least for men with Gleason scores of 7 or less.

    Comment?

  15. Doug:

    (1) Most men with prostate cancer in America are not getting treated at “major institutions”. They are getting treated at VA hospitals and community hospitals. They simply don’t have access to places like Memorial Sloan-Kettering or the Mayo Clinic or to all the things like 3-T MRIs and genetic tests and FLA that we discuss here … for either financial or logistical reasons. For that reason alone, your generalization is simply not reasonable.

    (2) AS is the currently recommended management (according to the NCCN guidelines) for men with very low-risk disease and a life expectancy of 10 to 20 years and for many men with a life expectancy of more than 20 years; AS is also the recommended management for men with low-risk disease and a life expectancy of 10 years or more. It still isn’t being widely implemented outside the “major institutions” you refer to. Why? Medical conservatism and the difficulties in getting surgeons to change their behavior patterns and their beliefs.

    (3) Since FLA could be used to treat the vast majority of these men if they showed an increase in their Gleason score (from 3 + 3 = 6 to 3 + 4 = 7 or 4 + 3 = 7), why would it make sense to treat them any earlier than necessary? They would gain no discernable clinical benefit, and FLA is not a completely side effect-free procedure.

    (4) I agree that FLA may be a highly appropriate form of therapy for some men with a life expectancy of 10 years or longer and organ-confined, low-volume, ideally uni-centric, Gleason 7 prostate cancer. AS is risky for such men anyway … particularly if they are about 70 years of age or younger (although it is not completely unreasonable for at least some of those men with Gleason 3 + 4 disease and a very slowly rising PSA level).

  16. Sitemaster and all,

    I agree with most of your comments, being 61, when I was diagnosed with Gleason 6 in August 2014, with a number of factors leading to a poor prognosis, I opted for FLA. I would not have opted for whole gland treatment and would have chosen AS if FLA were not available. A nodule was noticed on my prostate in 2005 so I had essentially been on AS for almost 10 years. For me, waiting for things to get worse and risk metastasis did not make sense.

    I think that there are a whole lot of men with Gleason 3 + 3 or 3 + 4 with 1 to 3 focal points that could benefit from focal treatments. All too often they are pushed toward whole gland therapies.

    I agree that, unfortunately, FLA is not a possibility for the general population due to the fact that there are only a handful of doctors qualified to perform the procedure, insurance coverage issues, and proximity to a doctor that can perform the procedure. Hopefully, this will change when Dr. Peter Pinto publishes his results from a 5-year trial on FLA at NIH, this coming spring. All indications are that the results will be extremely positive. This should move Medicare towards covering the procedure and more doctors getting trained.

    I am not trying to push FLA, but I do think that men need to know that FLA and other focal therapies are an option if your circumstances qualify you as a candidate. Right now, the vast majority of Docs do not even mention it as a possibility.

    Thanks for the work you do and information you provide.

    Henry

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