Re-classification rates on repeat biopsy for men on active surveillance in the Hopkins cohort


So there is an interesting new paper on the ramifications of active surveillance in the forthcoming June issue of the Journal of Urology — based on the extensive data now collected by the Johns Hopkins group through their very conservative active surveillance cohort of > 1,200 men accumulated since 1995.

The new analysis by Alam et al. is limited to the outcomes of patients who had at least low-risk disease and met differing sets of criteria.

  • First, to be classified as having very low-risk disease, they had to meet all of the following:
    • A clinical stage of T1c
    • A PSA density of < 0.15 ng/ml/cm3
    • A Gleason score of ≤ 3 + 3 = 6
    • A maximum of two positive biopsy cores
    • A maximum of 50 percent cancer in any one positive core
  • Or, to be classified as having low-risk disease, they had to meet all of these criteria:
    • A clinical stage of T1c or T2a
    • A PSA level of < 10 ng/ml
    • A Gleason score of ≤ 3 + 3 = 6
  • Second, regardless of their risk status, they had to  comply with the “annual” biopsy requirement established by Johns Hopkins.

For the purposes of this analysis, patients were considered to meet the second “annual” biopsy criterion if the interval between their repeat biopsies was 18 months or less.

Note that a man who met all of the criteria defined for very low-risk disease could have a PSA level of 10 ng/ml or higher.

What Alam et al. set out to do was to look at the risk for reclassification of the status of these patients over time by measuring the time interval from diagnosis to re-classification in this cohort of men who met very strict enrollment and follow-up criteria. So here is what they found:

  • 557/1,298 men (42.9 percent) met the criteria for very low-risk disease and the biopsy criterion (Group A).
  • 251/1,298 men (19.3 percent) met the criteria for low risk disease and the biopsy criterion (Group B).
  • 490/1,298 men (37.8 percent) met the criteria for very low- or low-risk disease but did not meet the biopsy criterion (Group C).
  • Men in Group C tended to be older, to have lower PSA density levels at diagnosis, and to have fewer positive cores at diagnosis than the men in Groups A and B.
  • For the men in Group A
    • Median follow-up was 4.0 years (range, 0.0 to 18.0 years)
    • 14/557 (2.5 percent) died of something other than prostate cancer during follow-up.
    • 54/557 (9.7 percent) either withdrew from the study or were lost to follow-up.
    • 126/557 (22.6 percent) were reclassified by Gleason score (of whom 72 or 57.1 percent were reclassified within the first 2 years).
    • 273/557 (49.0 percent) were re-classified based on any biopsy-related criterion, including Gleason score (of whom 164 or 60.0 percent were reclassified within the first 2 years).
    • 245/571 (44.0 percent) were still on active surveillance.
  • For the men in Group B
    • Median follow-up was 3.0 years (range, 0.0 to 18.0 years)
    • 8/251 (3.1 percent) died of something other than prostate cancer during follow-up.
    • 10/251 (4.0 percent) either withdrew from the study or were lost to follow-up.
    • 109/251 (43.4 percent) were reclassified by Gleason score (of whom 69 or 63.3 percent were reclassified within the first 2 years).
    • 136/251 (54.1 percent) were re-classified based on any biopsy-related criterion, including Gleason score (of whom 83 or 61.0 percent were reclassified within the first 2 years).
    • 128/251 (50.9 percent) were still on active surveillance.
  • During the first 2 years on active surveillance, there was no significant difference in re-classification rates between men in Groups A and B.
  • After the first 2 years on active surveillance, men in Group B were 1.8 times more likely to be re-classified than men in Group A.
  • Beyond the first 2 years on active surveillance, men in Groups A and B who had not been re-classified had a 35 percent decrease in risk for re-classification with each subsequent biopsy.

Now one can choose to look at these data in two different ways:

  • Either, one can think, “See, about 30 percent of the men who go on active surveillance progress very quickly, within 2 years.”
  • Or, one can think, “See, the men who are still found to be good candidates for active surveillance after their first, careful repeat biopsy are at a rapidly decreasing risk for progression and re-classification.

We are merely going to point out that Alam et al. themselves state the following:

Because most men in our series underwent 12- or 14-core biopsies only, misclassification at diagnosis could explain the high re-classification rate within the first 2 years.

In other words, as we get better at making sure, through a really careful repeat biopsy within 12 months after initial diagnosis, preferably under MRI/TRUS fusion biopsy or similar, that patients on active surveillance really do meet at least the low-risk criteria, there is the potential to believe that one should see re-classification rates like this drop after that first re-biopsy.

It is also worth noting that because the men in Group C were generally older, had lower PSA density levels at diagnosis, and had fewer positive cores at diagnosis than the men in Groups A and B, it is not unreasonable to appreciate that they may have felt less need to get repeat biopsies at least every 18 months. However, it would have been interesting to know the re-classification rates of these 490 men too.

The other important factor to take away from this paper is that 373/808 or 46.2 percent of the patients who met the stringent criteria required by the Johns Hopkins protocol were still on active surveillance over the study follow-up period.

3 Responses

  1. “Beyond the first 2 years on active surveillance, men in Groups A and B who had not been re-classified had a 35 percent disease in risk for re-classification with each subsequent biopsy.”

    Is “disease” a spell check for “decrease”?

  2. Dear Michael … Yes … Thank you … It is now corrected.

  3. Active surveillance (AS) stands up as a tool to assess the harmlessness or seriousness of lower risk prostate cancer cases

    This study is consistent with other evidence that the first 2 years on AS are key in assessing whether the disease is truly indolent or whether it has some stealthy aggressive aspects. AS helps smoke out the wolves that are trying to hide among the sheep.

    It is very good to see the evidence mounding up that AS works very well, especially when that evidence is from one of the larger and longer running series. Perhaps someday the US Preventive Services Task Force will appreciate this evidence and will be nudged to recover from the horrible blunder they made — blinded to the science — in their recommendation against screening for prostate cancer.

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