Picking the right men for initial management on AS

At the recently completed Canadian Uro-oncology Summit in Toronto, Dr. Laurence Klotz gave a very thorough update on active surveillance (AS) and its application in the management of lower-risk forms of localized prostate cancer. A detailed commentary of Dr. Klotz’s presentation is provided by Dr. Hanan Goldberg on the UroToday web site.

The following is a bullet-point summary of Dr. Klotz’s current views as expressed at this meeting:

  • There continues to be increasing appreciation of the value of AS in the management of localized prostate cancer and the minimization of risk for over-treatment of lower-risk forms of the disease.
  • We continue to learn more about the prognosis of specific patients with low- and intermediate-risk forms of localized prostate cancer based on their baseline parameters.
  • The role(s) for multiparametric MRI in the diagnosis, prognosis, and management of men on AS continue to evolve, but have become far more common that they had been.
  • It is now very clear that the metastatic potential of true Gleason pattern 3 prostate cancer is zero, but …
    • Misattribution of Gleason grade at the biopsy (particularly at the initial diagnostic biopsy) is “quite common” — i.e., in 25 to 30 percent of cases.
    • Biological grade progression of apparently Gleason 3 + 3 = 6 prostate cancer does seem to occur over time (at a rate of 1 to 2 percent of patients per year).
  • There is a diverse genomic landscape of clinically low-risk prostate cancer.
    • In men with Gleason Grade group 1 prostate cancer, there is a 2 percent score for genetic aberrance and aggressiveness.
    • In men with Gleason Grade group 2 prostate cancer, there is a 14 percent score.
  • The selection criteria for AS has varied considerably among the different centers conducting long-term AS cohort studies, and it is important to recognize this in evaluation of the reported data from the different centers.
  • AS has now been shown to be safe and effective in younger patients (< 60 years at diagnosis) as well as in older ones (≥ 60 years) with
    • Similar treatment rates
      • 74 percent in men < 60 years
      • 71 percent in men ≥ 60 years
    • Similar outcomes over time
      • Metastasis-free survival of 99.7 percent in men < 60 years
      • Metastasis-free survival of 99.0 percent in men ≥ 60 years
      • Prostate cancer-specific survival of 100.0 percent in men < 60 years
      • Prostate cancer-specific survival of 99.7 percent in men ≥ 60 years

Dr Klotz and the Sunnybrook group now consider that AS is an appropriate form of first-line treatment for the following sets of patients

  • Men with low-risk or very-low-risk prostate cancer
  • Men with intermediate-risk prostate cancer who have
    • Gleason pattern 3 + ≤ 5 percent of Gleason pattern 4 (often artifactually upgraded)
    • Low-volume Gleason grade group 2 with a negative mpMRI
    • Low-volume Gleason grade group 2 with favorable tissue-based biomarker scores
    • The right balance between risk, age, and co-morbidity status

He did, however, note that we still need to be able identify which is the “right” tissue-based biomarker test for the “right” patient.

He also noted that AS may not ever be appropriate for patients who have germline mutations to ATM, BRCA1, and BRCA2 genes. This still needs to be resolved, but seems increasingly unlikely for men with germline BRCA2 mutations.

It is very clear from Dr. Klotz’s presentation that he and others feel that significant progress has been and continues to be made in the correct and appropriate identification of men who are good-quality candidates for initial management on active surveillance … but we are still in learning mode.

8 Responses

  1. Assume that is supposed to be prostate cancer specific survival of 100% in men age < or = 60.

  2. At 2% grade progression per year, 22% will have progressed in 10 years. Not every study gives results that low. An active surveillance model at Johns Hopkins, which had strict annual biopsies, attempted to separate the misclassifications from the true grade progression. They estimated that the true grade progression rate in the first 10 years was 12%-24%. A similar model estimated the rate of total grade progression (true progression plus correction of prior misclassification) at about 4% per year during the first 10 years, and they determined that the time for those Gleason 6s that progressed to a Gleason 7 took an average of 14 months. Clearly, careful monitoring is necessary for the first 15 years.

  3. Typo?

    “Prostate cancer-specific survival of 10 percent in men < 60 years"

  4. Yes. Sorry. Will be corrected in 15 seconds.

  5. Dear Allen:

    The models all depend on the assumptions that went into them, and several of the models did not include something that really is essential before someone is formally entered into a high-quality AS protocol today: a multiparametric or at least a biparametric MRI scan (to avoid the need for a gadolinium-based imaging agent) and a repeat biopsy under MRI/TRUS fusion biopsy within 12 months of the initial diagnostic biopsy.

    “Progression” on AS within the first 12 to 14 months is usually not really “progression” at all. It is the finding of higher grade cancer that was almost certainly there at the time of initial diagnosis but which was not found on an initial 12-core blind biopsy.

    And on top of that, the whole point of active surveillance is that it is should involve a careful monitoring process over time. AS that does not involve careful monitoring over time is little better that watchful waiting.

  6. Simply, any man who, along with his treating physician, decides AS is a reasonable option, should still continue close “actual” active surveillance with appropriate diagnostics while in that AS status; if that doesn’t become the case, then the option is relegated to the old “watchful (just watching?) waiting!” This paper does not continue into what those appropriate diagnostics should be once a man begins the AS option. And, it is interesting (and important) to recognize that any man with germline BRCA2 mutations are not to be considered for AS.

  7. Dear Chuck:

    The “appropriate diagnostics” are going to depend on the initial status of the individual patient and any changes in his status over time. There is no “one size fits all” set of diagnostics that should be used for all AS patients over time.

  8. Dear Sitemaster,

    I didn’t intend to mean one size fits all, but there are several pretty well set considerations that should be included for every man on AS and yes, likely others depending on individual status.

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