Yes, you are at risk … but risk of exactly what?

An article just published in Urologic Oncology has reported — perhaps not surprisingly — that men who have a single, initial negative biopsy as a consequence of suspicion of prostate cancer are at significant risk for actual diagnosis of prostate cancer over the next 20 years.

This paper by Sayyid et al. is based on data from a cohort of 95,675 men who received a single, initial negative prostate biopsy in Ontario, Canada, between 1994 and 2014 — and of course most of the early biopsies would have been TRUS-guided six-core as opposed to systematic 12-core biopsies, and the vast majority would have been done without the benefit of a prior MRI. (See also this report in Renal & Urology News.)

Now we know that the development and diagnosis of prostate cancer correlates strongly with patient age, and this is a key factor in understanding some of the findings reported by Sayyid and his colleagues, as follows:

  • Average (median) follow-up of all patients was 8.1 years.
  • 31.5 percent of the initial cohort of 96,675 men went on to have at least one repeat biopsy.
  • The cumulative data at 20 years after the initial negative biopsy among all patients showed
    • A prostate cancer diagnosis rate of 23.7 percent
    • A prostate cancer-specific mortality rate of 1.8 percent
  • 629/96,675 men (0.65 percent) went on to die of prostate cancer.
  • The cumulative data at 20 years after the initial negative biopsy also showed
    • A prostate cancer-specific mortality rate of 3.2 percent among 18,417 men who were 70 to 79 years of age at that initial biopsy
    • A prostate cancer-specific mortality rate of 6.4 percent among 1,982 men who were 80 to 84 years of age at that initial biopsy
  • Higher socioeconomic status and urban residence were associated with
    • A higher probability of later diagnosis of prostate cancer
    • A lower probability of prostate cancer-specific mortality

However, … there are critically important data missing on all of these men. We don’t know anything about their

  • PSA level(s) prior to biopsy
  • Clinical stage at time of biopsy
  • Family history of prostate cancer (if any)
  • Ethnicity
  • Biopsy-derived Gleason score at actual diagnosis
  • Number of biopsy samples actually taken
  • Imaging data at time of biopsy

And we don’t know most such data for either their initial biopsy or later biopsies

Consequently, we have no meaningful insight into the risk categories of these 96,675 men either initially or when they were actually diagnosed, and without such insight it is extremely difficult to assess what this paper is actually telling us.

Clearly, in the 20,399 men who appeared to need a biopsy when they were between 70 and 84 years of age, but whose initial biopsy was negative, there was a higher risk for prostate cancer-specific mortality than there was among the 75,276 men who were between 40 and 69 years of age at the time of their first negative biopsy.

Also clearly, there is therefore a significant risk of dying of prostate cancer even if you aren’t diagnosed until your 70s or 80s.

On the other hand, this is not exactly new or surprising information (although it is certainly of epidemiological and academic interest).

The unanswered question we are faced with, however, is this one:

  • What percentage of men ≥ 70 years of age in this cohort were given at least one unnecessary biopsy in Ontario between 1994 and 2014 because either they were never diagnosed with prostate cancer on repeat biopsies or, even if they were diagnosed with prostate cancer, they were diagnosed with low-risk forms of the disease that presented no risk to their life or even their health and the quality of their life?

It is certainly very important for us to gain better understanding into the risk for diagnosis with clinically significant prostate cancer that could lead to prostate cancer-specific mortality among men in the 70s and early 80s. However, what may be even more important is the avoidance of over-diagnosis and over-treatment of men of these ages whose real “risk” is for clinically insignificant prostate cancer that is unlikely to have significant impact on their health or their lifespan.


2 Responses

  1. “would [not] have been done without the benefit of a prior MRI”?

  2. Dear SUM:

    If you’re not careful I shall start sending you these pieces to review before I put them up on the site! :O)


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