How accurate is an initial, negative prostate biopsy at predicting risk for prostate cancer-specific mortality?

A new paper in this week’s issue of Lancet Oncology comes from analysis of data on the outcomes of > 60,000 men given a prostate biopsy for risk of prostate cancer in Denmark between 1995 and 2011 and followed for up to 20 years thereafter.

Klemann et al. used data from the Danish Prostate Cancer Registry to explore the risk of overall and prostate cancer-specific mortality in men with an initial benign (i.e., negative) set of biopsy data. In other words, they looked at just how many men ended up dying of prostate cancer when they had no sign of prostate cancer in their prostates on their first biopsy.

It’s important, in looking at these data, to appreciate that, in Denmark, the national prostate cancer registry includes information on all men whose initial prostate biopsy tissue (and whose subsequent surgical or repeat biopsy prostate tissues) undergo histopathological examination; it is a truly national database. So, …

The study database included all men in Denmark who had a prostate biopsy over the 17-year period from January 1, 1995, to December 31, 2011. Follow-up data was examined as of April 28, 2015, and included prostate cancer-specific mortality and all deaths from other causes (which could also be extracted from the Danish national database system).

Here are the study findings:

  • The database included 64,430 men who had had an initial TRUS-guided prostate biopsy within the study period.
  • 63,454 men (98.5 percent) were eligible for inclusion in the study (because all relevant data was available).
  • The average (median) follow-up was 5.9 years
  • The total follow-up (from enrollment of the first patient until extraction of data on causes of death) was 20 years.
  • Among the > 35,000 men who had an initial biopsy result that was positive for prostate cancer
    • 10,407/35,159 men (29.6 percent) actually died of prostate cancer
  • Among the > 27,000 men who had an initial biopsy result that was negative for prostate cancer
    • 541/27,181 men (2.0 percent) actually died of prostate cancer
  • The actuarial estimate of 20-year all-cause mortality for all 63,454 men was 76.1 percent
  • The cumulative incidence of prostate cancer-specific mortality at 20 years was
    • 25.6 percent among all men in the study
    • 5.2 percent among all men in the study who had an initially negative prostate biopsy
      • 0.7 percent when the men had an initially negative biopsy and a PSA level of ≤ 10 ng/ml (n = 2779)
      • 3.6 percent when the men had an initially negative biopsy and a PSA level of > 10 and ≤ 20 ng/ml (n = 855)
      • 17.6 percent when the men had an initially negative biopsy and a PSA level of > 20 ng/ml (n = 454)
  • The cumulative incidence of non-prostate cancer-related mortality at 20 years was
    • 50.5 percent among all men in the study
    • 59.9 percent for men in the study who had an initially negative prostate biopsy

The authors present the following interpretation of their study data:

The first systematic transrectal ultrasound-guided biopsy set holds important prognostic information. The 20-year risk of prostate cancer-specific mortality in men with benign initial results is low. Our findings question whether men with low PSA concentration and a benign initial biopsy set should undergo further diagnostic assessment in view of the high risk of mortality from other causes.

Now this is a reasonable interpretation of the study results — when applied in general. Based on these data, if your initial PSA level is < 10 ng/ml and you have a negative initial biopsy result, there is an 0.7 percent chance (i.e., 1 in 143) that you will subsequently die of prostate cancer within the next 20 years. If one were to be 70 years of age at the time of that initial prostate biopsy, you might very reasonably decide that you never wanted another prostate biopsy at all.

However, the applicability of these results and this interpretation arguably become less reasonable for patients who are younger. If you have a PSA of 9.0 when you are 55 years of age, and your prostate biopsy is negative, then yes, you only have an 0.7 percent chance of dying of prostate cancer by the time you are 70, but what about when you are 80? And what if you PSA has risen to 10.1 ng/ml or higher the following year? Then you risk of dying from prostate cancer has risen to 3.6 percent or 1 in 28 men.

We haven’t seen the complete text of this paper, just the abstract, so we don’t know if the authors were able to make any assessment that correlated risk for prostate cancer-specific mortality with age at first biopsy (which would be interesting). What this paper does do, however, is add to the current knowledge about the very low risk for prostate cancer-specific mortality among men of 70 years and older who may well have an elevated PSA level but then have a negative biopsy result.

Lancet Oncology also carried an editorial commentary by Emberton on the data from this study. As yet we haven’t been able to read the full text of that commentary either.

3 Responses

  1. I assume that many of the men were already symptomatic by the time of the first biopsy, since 55% were biopsy positive (compared to about a third in the US), and their PC mortality rate was 30% within a median 6 years of follow-up (which is a much lower survival rate than treated high-risk men in the US). I assume the average age at biopsy was very high if three-quarters of the men were dead of all causes (and half from other causes) after a median of 6 years. I think Denmark should reconsider their PSA screening guidelines — they seem to be waiting too long for a first PSA test.

  2. Allen:

    These data go back to 1995. Almost no European nation was even using the PSA test much back then … and PSA testing wasn’t even widespread then in the USA.

  3. The median follow-up here was only 6 years (maximum 20 years), and men in this study had biopsies through 2011 with follow-up through 2015, so most were biopsied relatively recently. Something is rotten in the state of Denmark.

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