From the past to the future … the appropriate use of active monitoring

A new article just published in the journal Cancer concludes that “active surveillance is underused” in the management of low-risk prostate cancer. However, one has to be careful about how one interpret the data in (and the conclusions of) this particular article.

The new article by Chamie et al. was published on line just last week, and commentary about this article is already appearing on sites like HealthDay and MedPage Today. It was also supported on publication by a media release from UCLA.

The problem with a good deal of the reporting on this article, however, is that it neglects the fact that Chamie et al. are reporting on men who were being diagnosed between 2004 and 2007 and were followed only through 2009. During that time frame, it would be true to say that active surveillance had still not been widely embraced and endorsed by large numbers of urologists, and so any form of monitoring was often not really active surveillance at all, but was more appropriately being thought of as “watchful waiting.”

So, first let’s get clear what Chamie and his colleagues are actually reporting and then we can discuss the implications.

Their paper examines data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare databases on 37,687 men, all aged 65 years or older, all diagnosed with prostate cancer between 2004 and 2007, and followed through to December 31, 2009. And here is what they were able to show:

  • 3,656 of these 37,000+ men were just being monitored (on either active surveillance or watchful waiting).
    • 1,972 men (52.5 percent) had a clinical stage of T1.
    • 1,642 men (44.9 percent had a clinical stage of T2.
    • 2,507 men (68.6 percent) had a Gleason score of 6 or less.
    • 865 men (23.7 percent) had a Gleason score of 7.
  • During the first 2 years after diagnosis
    • 166 men (4.5 percent) were on active surveillance (as defined in the study).
    • 3,490 men (95.5 percent) were on watchful waiting (i.e., monitored but not on active surveillance).
    • 2,569 men (69.2 percent) had < 4 PSA tests in this time frame.
    • 1,032 men (28.2 percent) had 4 to 8 PSA tests in this time frame.
    • Only 460 men (12.6 percent) had a repeat biopsy in this time frame
  • The frequency of PSA testing did increase after the first 2 years of the study, and had roughly doubled by the last 2 years of the study.

Now there is no doubt at all that experts in active surveillance would not generally have considered this type of monitoring to be active surveillance. It looks and smells (generally) like a weak form of watchful waiting. Chamie et al. only characterized men as being on active surveillance if — within the first 2 years post-diagnosis — they received

  • At least 4 PSA tests
  • At least 4 office visits
  • At least 1 repeat biopsy

Some would argue that even this was a less than assertive form of active surveillance.

Based on this study, a fair conclusion is that the vast majority of Medicare patients in this cohort, diagnosed between 2004 and 2007, who were placed on any form of monitoring, were

  • Being undermonitored
  • Were quite certainly not on a modern form of active surveillance

On the other hand, since all the men in the study were 65 years or older, it is hard to know exactly what percentage of them were really good candidates for active surveillance anyway. The study does not break down the age ranges of the men bveing monitored. It states only that,

the plurality of the cohort was ages 70 to 74 years, white, married, without any comorbid conditions, and diagnosed in a metropolitan environment in the west [of the USA]

Since most of them had clinical stage T1 tumors and a Gleason score of ≤ 6, and their life expectancy would have been of the order of 11 to 17 years (based on actuarial data), it certainly appears that they should have been being closely monitored on a true active surveillance protocol. But in 2004 there was no clear guidance as to what that really meant.

Thus, this paper by Chamie and his colleagues is really important because it gives us a baseline against which to insist on change. By 2020 The “New” Prostate Cancer InfoLink is very clear that the majority of the men with characteristics similar to those in this study should be receiving regular monitoring on a true active surveillance protocol, which probably implies:

  • A repeat biopsy within 12 months of initial diagnosis (preferably under MRI/TRUS fusion biopsy)
  • PSA testing every 3 or 4 months (along with an associated office visit for a DRE and to discuss any occurrence of symptomatic disease)
  • An annual multiparametric MRI
  • Additional biopsies as necessary based on PSA data, DRE results, MRI data, and any signs of clinical symptomatology.

We would note, however, that many centers of excellence no longer consider a simple rising PSA level to be an exclusive indicator for a repeat biopsy unless the PSA level is rising fast. Changes in PSA density levels to > 0.15 may be a better indicator of risk for progression than PSA levels themselves.

There is still a degree of variation from center to center about exactly who is a reasonable candidate for active surveillance, all centers would seem to agree that any man over 65 with a clinical stage of ≤ T2a and a PSA level of < 10 and a Gleason score of ≤ 6 and a PSA density of < 0.15 is a candidate for active surveillance is he has a life expectancy of 10 years. Some centers will offer active surveillance to men significantly younger than this who have the same characteristics — with the acknowledgement that such younger men probably do have a higher risk of needing treatment over time. And then there are a few centers (e.g., the Sunnybrook Center in Toronto) that will extend the PSA entry criteria out to more like 15 ng/ml and will also willingly consider active surveillance for men with small amounts of favorable intermediate-risk disease characterized by a Gleason score of 3 + 4 = 7 disease.

Hopefully, within another couple of years, we will have some greater consensus about both the entry criteria for active surveillance as well as the appropriate patterns for  monitoring these patients. At that point in time, we should be insisting that the term “watchful waiting” be restricted to men with a life expectancy of < 10 years who would not be expected to benefit from treatment in terms of the ability of such treatment to extend their life. Thus there would be some men who might be monitored on active surveillance from (say) age 65 to 75 but at that pont could simply be switched to watchful waiting since localized treatment would be highly unlikely to extend their life even if they did have disease progression.

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