“Long-term” data on FLA in the treatment of localized prostate cancer

An important new paper in the Journal of Vascular and Interventional Radiology has just provided us with the first large set of data on the outcomes of men with prostate cancer treated with focal laser ablation (FLA).

These data come from Walser et al. at the University of Texas Medical Branch in Galveston, TX, where Dr. Walser has been providing FLA as a first-line treatment option for prostate cancer for several years. For interested readers, the link provided will take you to the full text of this paper.

The core question being addressed by the authors is whether the treatment of low- to intermediate-risk prostate cancer using FLA can preserve sexual and urinary function with low morbidity while providing adequate oncologic outcomes.

According to Walser and his colleagues FLA was conducted on 120 patients with low- to intermediate-risk prostate cancer. This was an “in-bore” procedure, and MRI thermometry was applied to control tissue ablation.

At 6 and 12 months, patients had clinical and MRI evaluation at follow-up, and biopsies were used to assess suspicious areas. The patients were also asked to complete surveys related to their sexual and urinary function.

Here is a summary of the results reported:

  • The 120 patients were treated between 2013 and 2017.
  • Average (median) patient age was 64 years (range 45 to 86 years).
  • The average (median) PSA level of patients prior to treatment was 6.05 ng/ml.
  • Pre-treatment biopsy Gleason scores were
    • 3 + 3 = 6 in 37/120 patients (30.8 percent)
    • 3 + 4 = 7 in 56/120 patients (46.7 percent)
    • 4 + 3 = 7 in 27/120 patients (22.5 percent)
  • Clinical stages pre-treatment were
    • cT1c in 89/120 patients (74.2 percent)
    • cT2a in 26/120 patients (21.7 percent)
    • cT2b in 5/120 patients (4.2 percent)
  • FLA was actually applied to
    • A single tumor site in 72/120 patients
    • Two tumor sites in 47/120 patients
    • Three tumor sites in just 1/120 patients
  • Average (median) follow-up was 34 months (range, 17 to 55 months).
  • 22/120 patients (18.3 percent) had a positive biopsy after FLA.
  • 20/120 patients (16.7 percent) required additional oncologic therapy within 1 year after FLA, when biopsy confirmed cancer following abnormal MRI.
  • There was no difference between functional scores before and after ablation.
  • The average (median) PSA level decreased to 3.25 ng/ml at 12 months post-treatment (P < 0.001).
  • Tumor diameter above the median (odds ratio [OR] = 3.36) was the only significant predictor for a positive MRI imaging after treatment.

Walser et al. conclude in their paper that

One year after FLA, selected patients had low morbidity, no significant changes in quality of life, and 83% freedom of retreatment rate. Sexual and urinary function did not significantly change after FLA.

The question raised by this paper is whether — based on these data — FLA has really “raised the bar” (yet) in the treatment of the majority of clinically significant cases of prostate cancer.

It is very clear that FLA is an option for

  • Carefully selected patients with low-risk disease who do not wish to go on active surveillance
  • Carefully selected patients with low-risk disease who have been on active surveillance and decide to seek treatment instead of staying on AS — even if there is no progression of their disease
  • Carefully selected patients with favorable intermediate-risk disease who have been on active surveillance and decide to seek treatment instead of staying on AS — even if there is no progression of their disease

What appears to be a great deal less clear, based on these data, is whether FLA is a reasonable option for anyone who is initially advised to seek early treatment for (say) unfavorable, intermediate-risk prostate cancer.

As with all new techniques, Walser and his colleagues’ outcomes data clearly improved with experience. There were two patients who had rectourethral fistulas among the earliest patients, but no more later on. Most of the patients in this cohort were treated in 2015 and 2016, with only 17 being treated in 2017.

The authors have apparently come to the conclusion that “true” FLA comes with sufficient risk for disease recurrence as to make it unwise. They state in the paper that:

The preferred method now is hemiablation of the involved side of the prostate assuming this can be done safely (i.e., the ablation zone will not affect the nerves or rectum). …Hemiablation involved laser destruction of the peripheral and transitional zone on 1 side of the gland with avoidance of the nerve root bundle, urethra, and ejaculatory ducts.

The “New” Prostate Cancer InfoLink is fully appreciative of the theoretical “attractiveness” of FLA compared to traditional forms of treatment for localized prostate cancer (radical surgery, radiotherapy, etc.). However, it seems that it may take us rather longer than some might have expected to determine the precise place of true FLA in the treatment of localized prostate cancer — if it actually has one.

5 Responses

  1. I’m not at all sure that FLA is a good idea for low-/favorable intermediate-risk patients on active surveillance (AS). Ablation interferes with the ability to accurately read mpMRIs and biopsies (tissue necrosis interferes with the flow of fluids picked up by a DWI-MRI and makes Gleason patterns virtually unreadable).

    Also, because FLA is focal, it interferes with the ability to use PSA as a monitoring tool. Even with the lesser accuracy of the conventional AS monitoring tools, 17% required re-treatment within the first year. This is comparable to the 25% treatment rate after a year on AS in Klotz’s study. And then, how many in 2 years? in 5 years? in 10 years? And what is the failure rate and morbidity of re-treatments?

    Even if there are no fistulas, there is greater risk of morbidity than with active surveillance.

  2. Interesting. Thanks for posting.

    Unfortunately, the paper does not segregate results by the traditional risk categories. It is likely that the hefty proportion of low-risk patients (assumed based on data provided) enhances the overall success rate, which would mean that the success rate for intermediate disease patients would be lower. My impression is that the likely success rate, even with the short-term data available, is not competitive for intermediate-risk patients; however, the technology is obviously in early development and may have better results if it matures. I understand the argument that FLA might be attractive to some “carefully selected” patients with favorable intermediate-risk disease or low-risk patients who are uncomfortable with active surveillance.

  3. Dear Allen:

    There are, indeed, very serious questions about the logic of this, given Walser’s data.

    The problem, I suppose, is … what do you do if you are psychologically unable to cope with the idea of active surveillance but you want to minimize the risk for side effects of treatment? It is easy to argue that all forms of focal therapy are significantly less than perfect.

  4. You asked “What do you do if you are psychologically unable to cope with the idea of active surveillance but you want to minimize the risk for side effects of treatment?”

    Let’s look at <a href="http://“>focal photodynamic therapy (PDT or TOOKAD), for which there are published, detailed, 2-year side effects, side-by-side with some toxicity outcomes of SBRT treatment. This is not a randomized comparison, so it should only be taken as ballpark comparisons. The list below shows the highest incidence of side effects reported by both studies. I chose this Georgetown study because they gave 2-year outcomes and because they included Grade 1+ toxicity — often only Grade 2 or higher toxicity is reported. As with focal therapy, almost all of the side effects were mild (Grade 1) and acute, occurring within the first month of treatment, and returning to baseline within 2 years. Potency retention was 79% at 2 years for SBRT; erectile dysfunction was 38% for PDT. Similar to focal ablation, only 1% had any serious (Grade 3) toxicity. However, none were life threatening.

    Grade 1+ side effects within the first 2 years after therapy:

    — Rectal bleeding: 4% PDT, 7% SBRT
    — Painful urination: 26% PDT, 29% SBRT
    — Urinary frequency/urgency: 11% PDT, 19% SBRT
    — Urinary incontinence: 10% PDT, 16% SBRT
    — Urinary retention: 10% PDT, 45% SBRT
    — Blood in urine: 29% PDT, 5% SBRT

    In the SBRT study, there were no biochemical failures in the first 2 years among the low-risk and intermediate-risk patients in the study. This compares to 51% with evidence of disease, and 28% with higher-risk prostate cancer already in the first 2 years for the focal PDT therapy, even with retreatment in some.

    If a man is psychologically unable to cope with the uncertainty of active surveillance, he creates even greater uncertainty for himself by choosing focal therapy because he loses or cripples his best monitoring tools. While radical therapy offers no guarantees of success, at least there are some well-validated tools for monitoring evidence of disease.

  5. An Unorthodox, Non-Focal Option for Appropriately Low-Risk Men Unable to Cope with the Idea of Active Surveillance for Prostate Cancer

    Sitemaster: Here is another option — one-time ADT3, plus maintenance

    One option not mentioned these days is going on a triple ADT program for about a year and then following it with continued use of Proscar (finasteride) as maintenance. Dr. Robert Leibowitz did pioneering work with that program for patients with T1 to T3 prostate cancer back in the late 1990s/early 2000s, prior to the advent of active surveillance (except in formal clinical series).

    Dr. Leibowitz’s data indicated a very high level of cancer control for his low-risk patients; we now know that these patients would have done fine, on average, with active surveillance, but his strategy also appeared to work well for an extraordinarily high percentage of his low-risk patients, which is superior to the usual results in an active surveillance program.

    His protocol, in essence, was to have his patients on ADT3 for about 13 months. Side effects gradually disappeared, generally, after the cessation of the LHRH agonist and antiandrogen components of ADT3. Also, based on the retrospective nature of Dr. Leibowitz’s main study (above), men who dropped out due to the side effect burden would not have been included in the data.

    He published at least one paper on his results, but it was retrospective and not in a major journal. He has also published a number of papers about his results in the PAACT newsletter and less formally. I know of two other large practices dedicated to prostate cancer that have used a highly similar but intermittent approach successfully for other groups of patients. I have seen no pertinent research that has put this approach for low-risk men to the test, and therefore I believe there is no research that effectively rebuts the gist of Dr. Leibowitz’s findings for low-risk men.

    I have one friend who was on this program for years (about a year of treatment followed by years of maintenance); he is now at about the 15-year point and has not had major treatment (but has annual or more frequent monitoring). This was also essentially the program I was on intermittently for my once life-threatening case between 2000 and 2013, when I had radiation therapy. I would resume the LHRH agonist and antiandrogen when my PSA was about 10 ng/ml and would take a vacation from these drugs when my PSA dropped to < 0.01, essentially. I later switched drugs a bit (and was always on Fosamax, Boniva, or Vivelle estradiol patches to protect bone mineral density), and my impression is that Avodart (dutasteride) would generally be a superior choice versus Proscar, but not for the few men who don't respond well to Avodart or experience bothersome side effects on that drug.

    All this said, I am convinced that active surveillance is the best approach for appropriate patients who find the strategy acceptable.

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