Active surveillance — a comprehensive review (with comment)

In another article in European Urology, Dall’Era et al. have provided a thorough review of published outcome data from the seven largest known series of patients being managed under active surveillance (AS). Unfortunately the full text of this article is not available on line.

The authors carried out a systematic and comprehensive search of all published literature from 1980 to 2011. Their goal was to identify all appropriate studies of active surveillance or watchful waiting that included a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention.

Their finding are good (to the extent that they confirm what we thought we knew) and less good (because they also confirm the existence of issues that need resolution).

Here are the key findings:

  • Data from seven large series of patients being managed on AS met study criteria and were systematically reviewed.
  • Eligibility criteria for inclusion in the seven AS studies vary very considerably, as do the full study protocols.
  • The longest, published, median follow-up period in any of these studies is still only 6.8 years (although data have been reported at medical/scientific symposia based on longer follow-up periods).
  • Prostate cancer-specific mortality of men enrolled on these AS studies remains low (at 0 to 1 percent).
  • Repeat biopsy with a minimum of 12 cores appears to be important and customary for monitoring changes in tumor histology.
  • Up to 33 percent of patients receive deferred therapy after a median of about 2.5 years of surveillance.
  • The definitive triggers for intervention with deferred therapy again vary among institutions and include
    • Histologic reclassification based on re-biopsy ( in 27 to 100 percent of cases)
    • PSA doubling time < 3 years ( in 13 to 48 percent of cases)
  • Between 7 and 13 percent of men receive deferred treatment despite no evidence of progression (i.e., because of anxiety and other reasons).

Dall’Era and his colleagues conclude that AS offers a real opportunity to limit intervention to patients who will likely benefit the most from radical treatment; that AS comes with a low risk of prostate cancer-specific mortality in the short to intermediate term; and that early, confirmatory biopsy (with a minimum of 12 biopsy cores) is essential for limiting risk of under-estimation of tumor grade and tumor volume.

However, the degree of variation in eligibility criteria for active surveillance is still potentially disturbing because, as yet, we are unable to offer any sound, evidence-based criteria for initiation of active surveillance to community-based physicians. The National Comprehensive Cancer Network (NCCN) guidelines strongly recommend monitoring as the primary, first-line form of management for two groups of men:

  • Men with a life expectancy < 20 years with very low-risk prostate cancer (defined by a clinical stage of T1c, a PSA level < 10 ng/ml, a Gleason score of ≤ 6, a PSA density of ≤ 0.1 ng/ml/g, fewer than 3 biopsy cores positive for cancer, and ≤ 50 percent of any positive core to be cancerous)
  • Men with a life expectancy of < 10 years with low-risk prostate cancer (defined by a clinical stage of T1-T2a, a PSA level < 10 ng/ml, and a Gleason score of ≤ 6)

These are “safe” recommendations — but they are not truly evidence-based. What they unfortunately do not address is the real issue of what we mean by “indolent” prostate cancer. If a significant percentage of prostate cancers truly are “indolent,” then they are just as indolent when they are found in men of 40 as they are in men of 85. Neither of these patients should be advised to have any form of immediate treatment, but we have no way to really define “indolent” disease.

There is still a long way to go if we are to be able to accurately resolve Whitmore’s paradox — that while cure may well be possible in those for whom it is necessary, the issue is whether it necessary for those in whom it is possible!

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