Upgrading after re-biopsy in the Sunnybrook active surveillance cohort

In another key paper to be presented at the Genitourinary Oncology Symposium in Orlando tomorrow, Klotz and his colleagues have provided data on the rate of pathological upgrading at re-biopsy in their large cohort of patients on active surveillance at the Sunnybrook Health Sciences Center in Toronto.

This paper by Jain et al. includes data on all patients in the Sunnybrook active surveillance cohort who have received at least one repeat biopsy after their initial enrollment into the prospective database. A pathological upgrade was defined as a finding of an upgrade from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7 or higher or an upgrade from Gleason 3 + 4 = 7 to Gleason 4 + 3 = 7 or higher (depending on the patient’s original Gleason score at enrollment into the study cohort).

Here are the major study findings:

  • 593/862 patients in the cohort (68.8 percent) had at least one repeat biopsy.
  • Average (median) follow-up was 6.4 years (with a maximum follow-up of 20.2 years).
  • The total number of biopsies ranged from 2 to 6 in any individual patient.
  • The risk status of the patients in the cohort at baseline was as follows:
    • 79.7 percent were low risk.
    • 20.0 percent were intermediate risk.
    • 0.3 percent were high risk.
  • 185/593 patients (31.2 percent) were upgraded while on active surveillance.
  • The proportion of patients upgraded increased with time, suggesting that prostate cancer de-differentiated at a rate of 1.0 percent/year in this cohort.
  • The estimated rate of increase of upgrading was 2.5 times higher in patients with intermediate-risk disease at diagnosis (rate, 1.9 percent/year) compared with those with low-risk disease (rate, 0.75 percent/year).
  • 114/185 upgraded patients (61.6 percent) went on to have active treatment.
  • Compared to patients who were upgraded but remained on active surveillance, the patients who were upgraded and treated had
    • Significantly higher PSA velocities (median 1.2 ng/ml/y vs 0.42 ng/ml/y, p = 0.01) and
    • Significantly higher Gleason scores (21.8 percent Gleason 8 to 10 vs 2.8 percent, p<0.01).

The authors report that this is the largest re-biopsy cohort of men on active surveillance reported to date and conclude that rates of prostate cancer de-differentiation over time “appear higher in patients with intermediate risk prostate cancer compared with those who are low risk at baseline.” This conclusion is hardly a surprising one, and it does raise the question whether men with Gleason 7 disease (whether 3 + 4 or 4 + 3) are really good candidates for active surveillance unless they have serious co-morbid conditions and/or a life expectancy of < 10 years.

3 Responses

  1. Thanks as always for being our eyes, ears and especially mind in the field!

    This is interesting and should be encouraging to low-risk men on prostate cancer who choose active surveillance.

    Dr. Klotz has some patients in the cohort on finasteride, and perhaps on other lifestyle interventions. I’m wondering if he will some day look into how they might affect upgrading on biopsy. If you see him, would you mind asking?

    (On a personal note, having fiducials implanted today.)

  2. “it does raise the question whether men with Gleason 7 disease (whether 3 + 4 or 4 + 3) are really good candidates for active surveillance unless they have serious co-morbid conditions and/or a life expectancy of < 10 years."

    Indeed. I'm a bit surprised that any men with Gleason 7 are considered for active surveillance unless they have these other conditions.

    Also, I can't reconcile the upgrade rate (maximum 1.9 percent/year, average 1.0 percent/year) over an average of 6.4 years with a total upgrade of 31.2 percent. The upgrade rate seems too low for the total upgrade.

  3. Some 23 years ago Dr. Tribukait reported a 23% probability of tumor dedifferentiation after 24 months using needle biopsies. Why has it taken so much time to recognize that? Guess it is par for prostate cancer. …

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