Numbers progressing and time to progression on active surveillance

A new study just published in the World Journal of Urology has provided us with data from the Prostate Cancer Outcomes Registry — Victoria (in Australia) on the progression of men initially managed on active surveillance.

At this point in time we continue to feel that it is important to emphasize that something like a third to half of men who are initially managed on active surveillance are going to show signs of disease progression if they are followed for long enough. Active surveillance is not a “treatment” for prostate cancer. It is a method of managing the disease until it becomes clear whether or not each individual patient really does need to have treatment.

So the new study by Sampurno et al. looked at data from nearly 1,000 newly diagnosed prostate cancer patients in the State of Victoria who were diagnosed with Gleason 3 + 3 = 6 prostate cancer, who were in initially managed on active surveillance, and who all received at least one repeat biopsy during their follow-up on active surveillance.

We can summarize the study findings as follows:

  • The study included 951 patients with low-risk prostate cancer.
  • The median patient follow-up was 2.2 years.
  • 39 percent of the patients had their Gleason score upgraded to 3 + 4 = 7 or higher during the follow-up period.
  • Compared to men initially diagnosed with clinical stage T1 disease, men initially diagnosed with T2 disease were 30 percent more likely to be upgraded (hazard ratio [HR] = 1.3; p = 0.048).
  • Gleason score upgrading occurred in
    • Half the men initially diagnosed with  clinical stage T2 disease within 1.6 years
    • Half the men initially diagnosed with clinical stage T1 disease within 2.7 years
  • Patients who were initially diagnosed at regional community hospitals and who had a follow-up biopsy at a metropolitan hospital were twice as likely to have a Gleason upgrade as men who had their initial diagnostic and their surveillance biopsies at metropolitan hospitals (adjusted HR: = 1.9; p = 0.029).
  • Other factors also increased risk for upgrading:
    • A percentage of cancerous core involvement of > 25.0 (adjusted HR = 1.6)
    • A PSA velocity of > 1.01 ng/ml/year (adjusted HR of 1.5 to 1.6)

The authors suggest that, when placing men on active surveillance and monitoring them over time, clinicians need to

… pay particular attention to the likely accuracy of the diagnostic specimen, their tumor stage, volume of tumor (percent of core involvement), and rising PSA.

They also note that men with clinical stage T2 disease, with > 25.0 percent of core involvement, and/or with a PSA velocity > 1 ng/ml/year

… should be counseled on the importance of following the recommended surveillance regimen.

At least in this cohort of “real life”, community-diagnosed patients, half had disease that progressed to a higher grade based on biopsy data within 2 years of diagnosis. Of course this does not mean that every patient who is upgraded from Gleason 3 + 3 = 6 to 3 + 4 = 7 when being monitored on active surveillance necessarily requires immediate treatment. Other factors would need to be taken into account in reaching conclusions about what to do for any particular patient (including things like the patient’s age, life expectancy, volume of cancer, and personal attitudes to his risk).

3 Responses

  1. Regarding the odds of Gleason score upgrading reported in the paper:

    It was not clear from the abstract how they determined that patients were placed on active surveillance.

    It seems almost a logical certainty that a more rigorously selected group for active surveillance would have decreased odds of upgrading on follow-up biopsy. In other words, here it appears the authors selected only patients with Gleason scores of 3 + 3 = 6 as “eligible” for AS, while in modern practice in the US factors like percentage of cores positive < 34%, PSA < 10, Gleason 6 or lower (or favorable Gleason 7), PSA density < 0.15, no felt nodules, and PSAV < 2 in combination have been used (2007 consensus, Dr. Peter Carroll). Of course now additional tools such as mpMRI and even genetic testing are being added.

    Sitemaster noted some non-disease factors that are very important.

  2. Dear Jim:

    With respect, I think you are over-analyzing the intent of this paper that is based on data from a patient registry. The authors’ sole significant point (in my opinion) is that among all the patients in the registry who were initially placed on active surveillance and who had a Gleason score of 6 at the time they were initiated on active surveillance, a very significant percentage were upgraded within a relatively short time frame.

    The question of whether all of the patients initially placed on active surveillance should or should not have been placed on active surveillance at all is a much more complex question. For example, the issue of how many of these patients had a confirmatory re-biopsy before they were actually placed on active surveillance is not discussed in this paper. My bet is that a lot of these men never had a formal re-biopsy prior to being managed on active surveillance and so their first follow-up biopsy was, in fact, the confirmatory re-biopsy. In that case it is hardly surprising that many of the men were found to have higher-grade disease than that found on their initial biopsy.

  3. Thank you.

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