Albertsen on the problems of screening and active surveillance

A paper just published in European Urology addresses pathologic outcomes among men initially managed with active surveillance and subsequently treated by deferred radical prostatectomy (RP). The paper stimulated an important set of editorial comments by Albertsen, which we strongly recommend to readers (along with the response from the authors of the original paper).

The original paper by Bul et al. is available in full on line. The authors set out to evaluate the pathological findings among a cohort of men participating in the so-called PRIAS study, in which men diagnosed with low-risk prostate cancer (defined as clinical stage T2, PSA < 10 ng/ml, PSA density < 0.2 ng/ml/ml, one or two positive biopsy cores, and Gleason 6) are initially managed on active surveillance. If patients show clear signs of risk reclassification — either because of a Gleason score > 6 or > 2 positive biopsy cores on a repeat biopsy or because of a PSA doubling time of < 3 years — they are then advised that a deferred RP (or some other form of treatment) may be appropriate. Men could also opt to have treatment simply because of anxiety about being on active surveillance or for other reasons, even if there was no increase in their risk level.

Bul et al. looked specifically at a cohort of men who went on to have a deferred RP after an initial period on active surveillance. Their data showed that:

  • The cohort comprised a total of 189 patients.
    • 143/189 men (75.7 percent) met protocol-based recommendations for deferred RP.
    • 24/189 men (12.7 percent) requested deferred RP because of anxiety.
    • 22/189 men (11.6 percent) had a deferred RP for other reasons (given in the full text).
  • Median time from initial diagnosis to RP was 1.3 years.
  • Relevant pathology results were available in 167/189 cases (88.4 percent).
  • 134/167 patients (80.8 percent) had organ-c0nfined disease.
  • 32/167 patients (19.2 percent) had extracapsular extension.
  • Gleason scores were
    • 3 + 3 = 6 in 79/167 patients (47.3 percent)
    • 3 + 4 = 7 in 64/167 patients (38.3 percent)
    • 4 + 3 = 7 in 21/167 patients (12.6 percent)
    • 4 + 4 = 8  in 3 patients (1.8 percent)
  • Unfavorable pathological results (pT3-4 disease and /or a Gleason score of 4 + 3 = 7 or higher) were identified in 49/167 patients (29 percent).
  • 33/49 men (67 percent) with unfavorable pathological results had a biopsy-associated reason for deferred RP.

The authors conclude that most men in this cohort (71 percent) initially followed on active surveillance still have organ-confined disease and favorable Gleason grading at the time of deferred RP and that, also in most cases, there was a sound protocol-based reason to switch from active surveillance to deferred RP.

So now let’s turn to Albertsen’s editorial (the full text of which is also freely available on line). We are not going to try to summarize this editorial because we really believe that this set of comments needs to be read in full. However, what we will do is quote two key sentences:

The main message coming from the paper by Bul et al. is that we have relatively poor tools to identify clinically significant PCa. While trials have shown that screening reduces PCa mortality, the absolute reduction is modest.

While Bul et al. note that future research needs to be focused on improving our ability to identify men at real need for curative therapy as opposed to active surveillance, Albertsen’s point is that — at present — we are still trying to identify and confirm the accuracy of the tools we need to do this. Could some form of imaging test be helpful here? Sure it could. Do we have well-established data demonstrating that such an imaging test is currently available? No, we don’t.

In their response to Albersen’s editorial, Bull and her colleagues make the very reasonable point that, until we have truly discriminatory tests, we are stuck with using what we have (the PSA test and various types of image-guided biopsy), and we will just have to do the best that we can with what is available.

One Response

  1. I wholeheartedly agree with Bul et al. that we need better tests for detecting significant prostate cancer. Until we do that, we are just playing roulette with whether to go with active surveillance or not. Yes, for most people, active surveillance may turn out to be better choice, but as an individual, I would probably choose immediate treatment as a safer choice.

    As a side note, I did find some statements in Albertson’s editorial as somewhat misleading. For example, I will disagree with his statement, “Given that PSA testing identifies an excessive number of men with potentially indolent Gleason 6 tumors, …” A high PSA value just raises a red flag with the chances of prostate cancer increasing with an increase in PSA value. But it is the prostate biopsy which determines the cancer and its grade (even though it could do better on that). Thus, PSA tests may be blamed for excessive biopsies, but not for finding excessive prostate cancer.

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