AS and management of Grade Group 2 prostate cancer


The abstract of a presentation to be given by Egan et al. — from the National Institutes of Health (NIH) at Bethesda, MD — at the upcoming, virtual Genitourinary Cancers Symposium has indicated that active surveillance (AS) seems to be a very reasonable option for first-line management for compliant patients initially diagnosed with Grade Group 2 prostate cancer.

These data come from a careful, retrospective review of 98 men enrolled on the AS protocol at the NIH, all of whom were initially diagnosed with Grade Group 2 disease, and all of whom had received MRI-targeted and systematic biopsies at time of enrollment. The patients were enrolled between 2007 and 2020. Patients were all monitored with annual MRI scans and PSA tests, and the majority of the patients were also given an annual, combined MRI-targeted and systematic prostate biopsy.

Patients with Grade Group 2, localized prostate cancer, a PSA level of < 10 ng/ml are considered to have favorable, intermediate-risk prostate cancer based on NCCN criteria.

Here are the core results of the study:

  • The average age of the 98 patients at enrollment was 64 years (and the majority were Caucasian).
  • Among these 98 patients
    • 62 (63 percent) showed no sign of progression
    • 36 (37 percent) progressed from Grade Group 2 to Grade Group 3 or higher while on AS (most of whom progressed to Grade Group 3)
  • Average (median) time to progression for the 36 patients who progressed was 71 months.
  • Average (median) PSA levels among these 36 patients were
    • 5.2 ng/ml at time of enrollment
    • 8.5 ng/ml at time of progression
  • Average (median) PSA densities among these 36 patients were
    • 0.12 at time of enrollment
    • 0.13 at time of progression.
  • The highest PI-RADS score on MRI for these 36 patients was largely unchanged.
  • Disease progression was the trigger for definitive treatment for these 36 patients.
  • All patients were alive at the end of the follow-up period.

Egan et al. conclude that:

AS is a reasonable option for compliant patients diagnosed with GG2 prostate cancer. While a significant percentage of these men will progress on AS, they do so at a median of 71 months, avoiding treatment-related harms of definitive therapy for over 5 years.

It is important to remember, in thinking about the overall value of AS as an initial management option, that the objectives of AS are

  • To defer treatment for the patient for as long as is reasonably possible while maintaining his quality of life
  • To ensure that treatment is implemented when it becomes apparent that there is a significant risk for onset of metastasis

AS is not a guarantee that any specific patient will never need treatment for their prostate cancer. Rather, it is a method for initial management of a patient with prostate cancer over time for as long as is possible (which may well mean that no treatment ever becomes necessary for some such patients). Based on this study, the 36 men who did progress over time deferred treatment for an average of 71 months (nearly 6 years), and the 62 men who did not progress were all still in process of deferring any treatment.

9 Responses

  1. Hi there
    Just wondering what 0.12 means in relation to PSA doubling times

  2. Would be very interesting to know how many of the 62 who did not progress opted for treatment???
    I recall the experience Peter Carroll often cites f rom his large AS cohort:
    1/3 progress
    1/3 opt for treatment
    1/3 remain on AS

  3. A third, essential aim of AS ought to be:

    — To commence potentially curative treatment in good time to avoid metastatic disease.

    While I fully accept that the treatment may well be worse than the disease, that is little consolation if the intervention is over-delayed, resulting in metastatic disease which a more timely intervention could have prevented. Lest we forget, it’s the metastases that kill, and cause most of the symptom.

    Bearing this in mind, it seems unlikely that a very small study, with no consideration of long-term outcomes, should be taken as a definitive guide to anything.

    All data on prostate cancer is useful; but this study does not — yet — provide enough useful data. Let’s hope the patients are still being followed for future presentations.

  4. Dear John:

    My mistake … that should have said “PSA densities” not “PSA doubling time”. Now corrected above.

    Thank you for bringing this to my attention.

  5. Dear Rick:

    As I understand it, none of these patients had opted for treatment if they were still Grade Group 2. Do note that Egan et al. describe this as a set of patients who were “compliant” with the AS protocol. It does not mean that there weren’t other patients who may have decided to have treatment even though they did not show any signs of progression.

  6. Dear heenan73:

    You seem to have entirely missed the point of the second objective of AS abovementioned, which is entirely focused on the importance of timely treatment when necessary and the consequent avoidance of metastasis!

    You also seem to keep missing the point of many of the commentaries on this web site. We are not trying to establish some sort of “truth” that applies to “all” patients. We are trying to inform patients about data that may affect their individual decisions. And we have explained carefully for some 20+ years that two men of the same age and health status and exactly the same prostate cancer diagnosis can very reasonably come to utterly different decisions about what they want to do about it — for all sorts of extremely complex reasons. There are very few “rights” or “wrongs” here.

  7. Dear Sitemaster:

    It’s a shame you are so intolerant of criticism of your utterly uncritical reviews of un-peer reviewed research (and I use the word critical in its correct definition).

    However, I have no wish to outstay my welcome, so goodbye.

  8. When I talk to patients about this, the key question I ask is. “What percent of the GS 3 + 4 is pattern 4?” Epstein at Johns Hopkins routinely provides this information, but not all pathologists do (another reason to get a second opinion from his lab!) According to the most recent ISUP guidelines, even 1 to 5% pattern 4 (with the rest pattern 3) is reported as GS 3 + 4. Such men are certainly good candidates for AS. Probably men with as high as 20% pattern 4 are still good candidates. Men with 25 to 33% pattern 4 are in an “iffy” situation, and, IMHO, men with any pattern 4 approaching 50% should be looking at immediate treatment.

    I also think that all men with GS 3 + 4 should get a biopsy-based Decipher test or a Prolaris genomic test (but not an Oncotype Dx test) to help inform treatment decisions.

    There are other considerations, such as location of a tumor close to the capsule edge (and, if available, a biopsy core through the capsule at that focus showing any infiltration). Also, men with any perineural invasion, cribriform pattern, IDC-P, or other rare subtypes should consider immediate treatment.

    With the recognition that “favorable intermediate-risk” and “unfavorable intermediate-risk” carry different prognoses, it is important to treat before the cancer crosses categories. Optimal treatments may vary with risk category. Brachy boost therapy has excellent outcomes for unfavorable intermediate-risk, but is over-treatment for favorable intermediate-risk, with unnecessary urinary toxicity.

  9. Sitemaster:

    Thank you for your last instructive comment!

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