Outcomes from a “watchful waiting” protocol for localized prostate cancer

A new study reports on retrospective analysis of data from a series of 218 patients diagnosed between 1991 and 2005 with localized prostate cancer and who were managed using a “watchful waiting” (as opposed to an active surveillance) strategy at the Massachusetts General Hospital (MGH).

According to Coen et al. these patients were followed using PSA monitoring and digital rectal examinations (DREs).

The top-line results of this study are as follows:

  • Average (median) age of patients at diagnosis was 71 years.
  • Average (median) PSA at diagnosis was 5.4 ng/ml.
  • Gleason scores at diagnosis were
    • Gleason 6 in 95 percent of patients
    • Gleason 7 in 4 percent of patients
    • Gleason 8 in 1 percent of patients
  • Clinical stages at diagnosis were
    • T1a,b in 6 percent of patients
    • T1c in 84 percent of patients
    • T2 in 10 percent of patients
  • Average (median) follow-up was 6.3 years.
  • Overall survival was 79 percent at 10 years.
  • Prostate cancer-specific survival was 100 percent at 10 years.
  • Re-biopsies were performed in 95/218 patients.
  • 5 percent of patients showed evident, distant metastasis.
  • 15 percent of patients received treatment with salvage androgen deprivation therapy.
  • 70 percent of patients were free of any clinical intervention.
  • 15 percent of patients had a PSA doubling time of ≤ 3 years.
  • 16 percent of patients had a PSA velocity of ≥ 2 ng/ml/yr
  • Among the 95 patients who received a follow-up biopsy
    • 25 percent showed an increase in their Gleason score (grade progression).
    • 33 percent showed an increase in the percentage of positive biopsy cores (volume progression).

The authors conclude that in a carefully selected series of patients, generally with low risk prostate cancer, watchful waiting appears to have been associated with low rates of clinical intervention and cancer progression. They further conclude that PSA doubling time and volume progression were the important triggers for clinical intervention, and state that these triggers will be incorporated into MGH’s current active surveillance protocol. (In that context, it is interesting to note the data from the Sunnybrook group, reported just the other day, suggesting that PSA doubling time is not necessarily a particularly good trigger for clinical intervention in patients on active surveillance!)

What is interesting about this paper is that, even under a much less structured “watchful waiting” protocol dating back into the early 1990s, some 70 percent of the carefully selected patients never required any form of intervention, that prostate cancer-specific mortality did not occur, and that only 5 percent of the patients ever showed evidence of metastatic prostate cancer. These data further substantiate the clinical utility of careful monitoring as opposed to active treatment for carefully selected patients known to have relatively low-risk prostate cancer — and particularly for such patients with an otherwise limited life expectancy.

4 Responses

  1. This is in line with active surveillance (AS) research that indicates AS is a worthy prime option for men with low-risk prostate cancer.

    It’s notable that the men in this study did very well despite not having the monitoring associated with AS. Someday it may be possible to relax a bit or refine the six consensus criteria associated with AS in the 2007 conference called by Dr. Peter Carroll (PSA level, Gleason score, stage, PSA density, PSA velocity, and percent of cores positive). Already there is some use of color Doppler ultrasound to refine AS eligibility.

    Does anyone know who is leading the MGH AS program, or when it started, or how large it is? Have they reported results?

  2. It is important to note that the average (median) age of patients at diagnosis was 71 years. With that in mind and considering the 100 percent prostate cancer survival at 10 years, active surveillance seems to be an excellent path to follow for patients of a certain age.

    It would be interesting to find out the 20-year prostate cancer mortality of younger patients, e.g. a median age of 50. For younger men, with a longer life expectancy of 25-35 years it may make more sense to choose a more aggressive treatment.


    Hi Reuven,

    I’m responding to your post of October 14, 11:03 PM in which you speculated that it might make sense for younger men to choose more aggressive treatment than AS.

    Of the six major AS programs that have been around a while and have reported results, probably a majority, maybe all of them, would have agreed with that at one time. Some may still agree, but a consensus of leaders in AS at that conference on AS called by Peter Carroll in 2007, mentioned in the first response here, was that age did not matter.

    For example, Dr. Klotz, who leads the Toronto program, has said that he looks for excellent eligibility criteria results for younger men entering AS and monitors them extra carefully in the early years, but he stated as early as 2007 that he was comfortable with patients of any age.

    When you think about it, a biopsy, perhaps stemming from a PSA rise due to infection, can happen to catch one of those indolent cases in a younger man, the kind that is never going to be a problem in his lifetime.

    I was glad to see that age was not included in the consensus eligibility criteria for active surveillance. (The criteria are: PSA level <10, PSA velocity <2, PSA density <0.15, Gleason score <7 (with some leeway for older and/or comorbid men in the Toronto and perhaps other programs), a DRE that is negative for nodules, and percentage of biopsy cores that are positive for cancer <34%. The concept in these consensus criteria is that a patient needs to be okay on all of these to be eligible for AS.) Some doctors are also adding color Doppler ultrasound or saturation biopsies to ensure a very strong likelihood of long-term success.

    The new book by Ralph Blum and Mark Scholz, MD, has very informative coverage of AS, including a recap of key points from the conference on AS in 2007. It has a chart showing the criteria on page 66.

  4. I’ve never understood why age is a criterion in the decision chain for AS where the diagnosis is a suitable one.

    The number or percentage of men who die from prostate cancer under the age of 60 is very small indeed, so a man with a low-risk diagnosis who is in his 40s has 20 years to go before he starts getting to the “danger zone” and almost 40 years to go until he gets to the median age for disease-specific death — half the men who die from prostate cancer are over the age of 80.

    A lot can happen in 40 years — but probably not prostate cancer-specific death for low-risk men.

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