Formal update on Sunnybrook active surveillance data at AUA annual meeting

Over the weekend, Klotz et al. provided interesting new information in the third and most recent, formal update of the prospective data from the active surveillance series being monitored at Sunnybrook Cancer Center in Toronto, Canada.

As indicated in the original abstract of this presentation (abstract no. PD-14-03; click here for access), and reported by Dr. Martin Hofmann of the University of California Irvine on behalf of UroToday, Klotz et al. report that:

  • The most recent analysis encompasses 840 men, all diagnosed with low- to intermediate-risk prostate cancer that was histopathologically confirmed within 12 months after enrollment in the study.
    • 206/840 patients have been followed for ≥ 10 years.
    • 60/840 patients have been followed for ≥ 15 years.
  • Intervention was offered to (but not necessarily required by) all those patients with a PSA doubling time of < 3 years, a Gleason score progression (to 4 + 3 = 7 or greater), or unequivocal clinical progression.
  • Primary outcome measures included overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients.
  • The percentages of patients who remain on active surveillance over time have been
    • 77.1 percent after 5 years
    • 63.4 percent after 10 years
    • 52.3 percent after 15 years
    • 52.3 percent after 20 years
  • 693/840 patients (82.5 percent) enrolled are still alive.
  • 147/840 patients (17.5 percent) enrolled had died as of this analysis.
  • 208/840 patients (24.8 percent) have elected to have treatment (for cause or by choice).
    • 44/208 patients (21 percent) have experienced biochemical progression (i.e., 5.2 percent of the total cohort)
    • Biochemical progression has been observed in
      • 11 percent of the patients electing to have surgery
      • 22 percent of the patients electing to have radiation therapy
    • 30/840 patients (2.7 percent) have developed metastatic prostate cancer.
    • 14/840 patients (1.7 percent) have died of prostate cancer (all of whom had metastatic disease prior to their deaths).
    • Another 16/840 patients (1/9 percent) had metastases at the time of this analysis.
  • The actuarial prostate cancer-specific  survival rates are
    • 97.9 percent at 10 years
    • 93.5 percent at 15 years
    • 86.3 percent at 20 years
  • The hazard ratio for non-prostate to prostate cancer-specific mortality was 9.7:1.

It has been clear for many years that no form of monitoring was going to be a “perfect” way to manage prostate cancer. In other words, men electing to have active surveillance as a primary management option (as compared to immediate intervention) were always going to be at some degree of risk for progression and potentially for metastatic disease and the possibility of prostate cancer-specific mortality. However, the 20-year actuarial cancer-specific survival rate of 86.3 percent in the Sunnybrook series (which includes men diagnosed with Gleason 3 + 4 disease and men with PSA levels at diagnosis of up to 15 ng/ml) is probably far higher than many had ever expected, and is confirmed by the fact that men in this series were nearly 10 times more likely to die of something other than prostate cancer than from prostate cancer itself.

The Sunnybrook series now includes > 1,000 patients, and it seems reasonable to believe that advances in methods for identification of higher risk patients (through the use of multiparametric MRI scanning, MRI/TRUS fusion-guided biopsies, and genomic testing) will allow Klotz and his colleagues to become far better at early identification of higher-risk patients than they were able to be when this study was initiated in the mid-1990s.

The “New” Prostate Cancer InfoLink is convinced that high-quality expectant management is an entirely appropriate form of care for many men being diagnosed today with very low-, low-, and some intermediate-risk forms of prostate cancer. However, we would add the proviso that has proven to be true (to date) for the use of any method for the management of prostate cancer: the skill and experience of the treating physician and his/her support staff is crucial to the overall outcome for individual patients. Active surveillance is no exception to that general rule, and patients who want to consider this management option would be wise to consult with clinicians who have skill and experience in the oversight and ongoing management of such cases.

10 Responses

  1. Was or is mpMRI being used in monitoring of patients? If perineural invasion was found on any pathology, would that kick the patient out of eligibility automatically?

  2. Dear Gerald:

    mpMRI has already been integrated into monitoring of men on active surveillance at several specialized practices in the USA and Canada, and probably in other countries too. What is not yet clear, however, are the “best practices” that need to be adopted in applying this technology. For starters, there is no uniformity among radiologists, as yet, about how to report what is being seen on such scans, and it takes considerable experience to interpret such scans with accuracy.

    With regard to perineural invasion, I don’t think anyone is clear on just how significant perineural invasion really is in men with otherwise low-risk or very low-risk prostate cancer. So it is hard to answer your question with any degree of accuracy. My suspicion is that perineural invasion would be a finding that is a strong indicator of the importance of a confirmatory re-biopsy, and that other factors (e.g., the age and life expectancy of the patient, as well as his general health, may become important in deciding whether active surveillance would be an appropriate form of care). I’d be surprised if anyone has an absolutely sound answer to this question as yet.

  3. Wow. 52% after 20 years remained on AS. How often did they undergo a biopsy?

  4. Sam:

    In the Sunnybrook series, all patients received an initial re-biobsy within 1 year of the initial diagnosis. However, Dr. Klotz and his colleagues have long understood that annual re-biopsies come with their own risks and so very few patients have received annual re-biopsies. As far as I can tell, re-biopsies have been occurring at more like 2- to 4-year periods depending on factors indicative of potential for risk (rising PSA levels, other clinical symptoms, etc.)

  5. I can testify to the lack of uniformity in reading mpMRI scans. I was told initially I had an extracapsular tumor involved in one nerve bundle. However, I have had four opinions that it was not outside the capsule at all from physicians who I feel are much more experienced with this technology.

  6. All I can really say is “Wow.” It would be interesting to compare the results of a comparable risk pool who chose immediate treatment. How many died directly from prostate cancer in spite of treatment?

    At least for the low-risk pool, it matters more what you have than what you do.

  7. I’m still aiming to be in the 86.3 per cent of survivors at 20 years!!

  8. From what I understand, this is very different from Peter Carroll’s UCSF cohort, which is about the same size but less mature — I think around 12 years. In that cohort, roughly one-third progress to treatment through disease advancement, one-third opt for treatment, and one third remain on active surveillance.

  9. Rick:

    If I assume these numbers to be correct, this may be telling us more about Americans’ levels of fear about the word “cancer” than it is about the effectiveness and safety of active surveillance in the management of low- and intermediate-risk disease.

  10. Absolutely, Mike … and another good reason to consider new terminology like IDLE.

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