Not all men with Gleason 8-10 disease are going to do badly after treatment

There is a perception among a lot of patients — especially when they get diagnosed — that having a high Gleason score of 8, 9, or 10 is essentially a “death sentence”, regardless of how they get treated. This is not actually the case at all. Plenty of men with Gleason 8 to 10 disease actually do well after treatment. And it has long been assumed that this was the case in particular if they were identified and treated early — while they had truly organ-confined disease.

A newly published paper by Fischer et al. has now confirmed this assumption through a careful retrospective analysis of data from > 450 men whose records could be identified in the SEARCH database, all of whom received surgical treatment for Gleason 8 to 10 prostate cancer.

Fischer and his colleagues set out to identify whether, among a large cohort of men who had pathologic Gleason scores of 8 to 10 after surgery, they could identify particular subsets who were at meaningfully greater of lesser risk for biochemical progression within 2 years of their surgery. To do this, they identified a total of 459 eligible patients within the SEARCH database and categorized these men into one of five different groups:

  • Group 1: Men with negative surgical margins, no extracapsular extension, and no seminal vesicle invasion (SM−/ECE−/SVI−)
  • Group 2: Men with positive surgical margins and no extracapsular extension, and no seminal vesicle invasion (SM+/ECE−/SVI−)
  • Group 3: Men with negative surgical margins and evident extracapsular extension, and no seminal vesicle invasion (SM−/ECE+/SVI−)
  • Group 4: Men with positive surgical margins and evident extracapsular extension, and no seminal vesicle invasion (SM+/ECE+/SVI−)
  • Group 5: Men with seminal vesicle invasion (SVI+)

They then used the data from these five groups of men to compare their risks for biochemical recurrence at 2 years, showing the following findings:

  • There was a clear correlation between pathological group and biochemical recurrence at 2 years post-surgery.
    • Patients in Group 5 had the highest risk for recurrence (at 66 percent).
    • Patients in Group 1 had the lowest risk for recurrence (at 14 percent).
    • Patients in Group 2, 3, and 4 all had comparable risk for recurrence (at about 50 percent).
  • Similar results were observed after adjustments were made to allow for variations in PSA level, age, and clinical stage.
  • Similar results were also observed after exclusion of men who received immediate adjuvant therapy.

In other words, men with pathological Gleason scores of 8 to 10 but who had negative surgical margins, no extracapsular extension, and no seminal vesicle invasion post-surgery had distinctly low risk for biochemical recurrence at 2 years post-surgery. However, having positive results for any one or more of these three characteristics significantly increased risk for biochemical recurrence within the same time frame.

There is nothing particularly surprising about these data. Indeed, they reflect very similar results to those predicted by the Kattan post-treatment nomogram for a 60-year-old man with a PSA of 9.5 at diagnosis and a pathological Gleason score of 8 who meets precisely comparable characteristics if his PSA drops to < 0.1 ng/ml at 3 months post-surgery, as shown in the following table:


On the other hand, it is helpful for patients to know that actual data from relevant retrospective analyses still continue to support the types of projections of nomograms like those developed by Kattan, Scardino, and their colleagues.

4 Responses

  1. Thanks for posting this interesting study.

    Does anyone have access to the numbers of patients out of the total number of 459 that were in each group? I’m wondering if that notably successful first group constituted a fairly hefty proportion of the whole group. (The group numbers were not in the abstract.)

    It would also be useful to know the span and “center of gravity” of the time frame of the patient database. It could be that many of the men in the study were not able to take advantage of the recent slew of impressive drugs for late-stage patients.

    This study is roughly similar in its prognosis function to the prognostic work on recurrences that Dr. Stephen Freedland, one of the authors here and now at Duke, did while he was at Johns Hopkins.

  2. Interesting study. I became concerned when I learned the meaning of Gleason 4 + 4. My general reaction was stoic in a Roman sense. I figured there was nothing besides maximally adequate treatment that anyone could do about cellular structure, and left it up to nature. But as I got radiotherapies, I wonder if anything analogous to the above can be said about that?

  3. George:

    Since one never really knows what the actual, pathological Gleason scores are for men who are treated using anything other than surgery, I don’t see any way to be able to develop a similar type of evaluation for men treated by radiotherapy of any type (or cryotherapy, or HIFU).

  4. Perhaps multi-parametric MRI (prior to treatment) will some day be able to give radiation patients and researchers on radiation patients insight to the pathology of their prostates, especially with the new “Epstein” grading system where the lowest grade groups those that are often not well detected by the mpMRI.

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