Active surveillance for men with Gleason 3 + 4 = 7 disease


The “New” Prostate Cancer InfoLink has taken the position for quite a while that active surveillance could well be a highly appropriate management strategy for some men  with a Gleason score of 3 + 4 = 7 at diagnosis (but far from all of them) — if they still met certain other criteria as good candidates for this form of management. The question (for us) has always been: How can we better determine which men with Gleason 3 + 4 disease might be “the best” candidates for active surveillance?

A new paper by a group of Korean researchers has now provided some initial suggestions that may be helpful in identification of such patients.

Kwon et al. (abstract or full text article) conducted a retrospective analysis of data from a total of 794 Korean patients, all of whom met relevant eligibility criteria and received a radical prostatectomy at their institution between January 2006 and December 2013. They classified these patients into two of three possible groups, as follows:

  • Group A comprised 577 patients who met active surveillance criteria used by any one of six well-recognized patient cohorts defined below, including having Gleason 3 + 3 = 6 disease.
  • Group B comprised 217 patients who met active surveillance criteria used by any one of the same six patient cohorts with the single exception that they could have Gleason 3 + 4 = 7 disease.
  • Group C comprised the entire cohort of 794 patients.

The active surveillance criteria of the six well-recognized patient cohorts were those used by: the Johns Hopkins cohort, in Baltimore, MD; the Memorial Sloan-Kettering Cancer Center cohort, in New York, NY; the University of Miami cohort, in Miami, FL; the University of California, San Francisco cohort, in San Francisco, CA; the University of Toronto cohort, in Sunnybrook, Ontario; and the PRIAS cohort in Europe. It should be noted that these six cohorts all have slightly different eligibility criteria for enrollment of patients and slightly different criteria for moving patients off active surveillance and on to invasive forms of localized treatment. The criteria used by Johns Hopkins and the University of Miami are generally recognized to be the most stringent; the criteria used by the University of Toronto are certainly the most inclusive.

Here are the study findings reported by Kwon et al.:

  • By comparison to patients in Group A, patients in Group B had, on average,
    • Significantly higher PSA levels at diagnosis (p < 0.001)
    • Significantly higher PSA densities at diagnosis (p < 0.001)
    • A higher number of positive cores at biopsy (p < 0.001)
    • A higher pathologic Gleason score at surgery (p < 0.001)
    • A higher pathologic stage at surgery (p < 0.001)
    • A higher proportion of unfavorable disease post-surgery (41.5 vs. 15.6 percent; p < 0.001)
  • By comparison to patients in Group A, all patients in Group C had, on average (at  a median follow-up of 38.5 months)
    • No significant difference in the proportion of unfavorable disease post-surgery for patients meeting 5 of the 6 sets of active surveillance criteria
    • A significant difference in the proportion of unfavorable disease post-surgery for patients meeting the University of Toronto criteria (p = 0.001)
    • No significant difference in biochemical recurrence-free survival for patients meeting any of the 6 sets of active surveillance criteria.
  • Looking at the patients in Group B,
    • Patients who met all non-Gleason 6 criteria from Johns Hopkins and the University of Miami showed no significant predictor of risk for unfavorable disease.
    • Patients who had a PSA density > 0.015 ng/ml/cm3 did have a significant risk for unfavorable disease.
    • Patients who had a Gleason 3 + 4 = 7 tumor length of > 4 mm did have a significant risk for unfavorable disease.
    • Overall, a PSA density of > 0.015 ng/ml/cm3 was a significant predictor of unfavorable disease (hazard ratio [HR] = 2.27; p = 0.011).
    • Overall, a Gleason 3 + 4 = 7 tumor length of > 4 mm was a significant predictor of unfavorable disease. (HR = 3.34; p = 0.011).
    • 34/217 men (15.7 percent) in Group B had neither a PSA density of > 0.015 ng/ml/cm3 nor a Gleason 3 + 4 = 7 tumor length of > 4 mm.
    • The proportion of unfavorable disease post-surgery in these 34 men was 14.7 percent (comparable to the 15.6 percent of men in Group A).

While we cannot use these data to say anything with certainty, for all sorts of reasons, they do offer a hypothesis, as follows:

  • Men with a Gleason score of 3 + 4 = 7 who meet all the active surveillance criteria applied by Johns Hopkins and the University of Miami (including a PSA density of < 0.015 ng/ml/cm3 and a Gleason 3 + 4 = 7 tumor length of > 4 mm) may be candidates for active surveillance who are just as good as those men in Group A above.

It does have to be stated clearly that the retrospective nature of this study, along with the limited median follow-up of the patients (at just over 3 years), do affect the power of the results of this study. However, these data do also appear to give strong support to the idea that roughly 15 percent of men with Gleason 3 + 4 disease are potentially good candidates for active surveillance. This rough estimate is similar to the expectations of The “New ” Prostate Cancer InfoLink (which we had always thought might be around 20 percent of men with Gleason 3 + 4 = 7).

3 Responses

  1. You state above “(including a PSA density of > 0.015 ng/ml/cm3 and a Gleason 3 + 4 = 7 tumor length of > 4 mm)” meet the criteria for active surveillance. It appears to me that you have your > incorrect and should read <.

  2. Let me add to my earlier response; in men with a Gleason score of 3 + 4 = 7, having either a PSA density of > 0.015 ng/ml/cm3 or a tumor length of > 4 mm are indications of having a “significant predictor of unfavorable disease,” and thus such men with one or both of these findings are probably not good candidates for active surveillance.

  3. Chuck:

    You were correct in your first statement and the symbol have been corrected above. In your second statement, I think that all we can say at this time is that, based on the data from this study, the evidence would suggest that, among men with a Gleason score of 3 + 4, only those who have a PSA density of < 0.015 ng/ml/cm3 and a tumor length of < 4 mm would appear to be good candidates for active surveillance … but that data from at least one other study would be helpful to confirm this hypothesis.

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