Active surveillance, upgrading on repeat biopsy, and consequent management

In February this year we commented on an article that argued in favor of active surveillance as an appropriate initial management strategy for “favorable” intermediate-risk prostate cancer.

A new article by Hussain et al. in the Journal of Urology (available as a full-text article) now appears to extend that argument to men already on active surveillance who are upgraded from low-risk disease to “favorable” intermediate-risk disease. In other words, Hussain et al. state that their study confirms that patients who are on active surveillance but have a slight upgrade in their status don’t necessarily have to rush into treatment. They can take their time to think through all of their options and come to a decision that really works for them as individuals … and it is not unreasonable to simply remain on active surveillance.

There is a nice discussion and summary of the data published by Hussain et al. on the Medscape Oncology web site (if you are signed up as a member of that web site, which is free). Basically, what the authors show is the following:

  • They conducted a retrospective analysis of a cohort of 219 men with lower risk disease managed initially with active surveillance (for a minim,um of 6 months) and upgraded to Gleason score 3 + 4 or higher.
  • Among this cohort of patients
    • 150/219 (68 percent) were upgraded to Gleason 3 + 4 = 7.
    • 69/219 (32 percent) were upgraded to Gleason 4 + 3 = 7 or higher.
  • Median time to upgrade after initiation of active surveillance was 23 months.
  • 163/219 patients (74 percent) sought treatment after their upgrade (most by radical prostatectomy).
  • The treatment-free survival rates at 5 years post-upgrade were
    • 22 percent for the patients upgraded to Gleason 3 + 4 = 7 disease
    • 10 percent for the patients upgraded to Gleason 4 + 3 or higher
  • Among the patients who were upgraded and treated by radical prostatectomy
    • 34 percent of cancers were downgraded on post-surgical pathology
    • 6 percent of cancers were upgraded on post-surgical pathology
  • Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (odds ratio [OR] = 3.33, p = 0.02).

The authors conclude that:

After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

It is worth noting that such relatively recent innovations as multi-parametric MRIs and molecular and gene expression profiling of biopsy tissue were not being used in the evaluation of any of the patients included in this cohort of patients. The authors are careful to note that  such innovations

appear to be promising tools to improve the differentiation between indolent and aggressive tumors, and may assist in identifying the subset of men who may benefit most from early treatment and those that can be put safely under surveillance.

3 Responses

  1. Love this. Excellent!

  2. The $64,000 question — that will take time to answer — is whether the cohort who elected primary treatment after being upgraded face a higher rate of recurrence than men treated initially with comparable disease demographics. This is the question we as advocates often have to answer — does active surveillance carry with it a greater risk of disease progression.

  3. Rick:

    The ProtecT trial from the UK is expected to give us the answer to that question … maybe as early as next year.

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