Swedish data support PCPT re-analysis: no increase in high-risk prostate cancer after use of 5-ARIs


Another study, just published in the British Medical Journal, appears to further debunk the idea that use of 5α-reductase inhibitors (5-ARIs) is associated with a significant increase in risk for development of high-grade prostate cancer.

This new Swedish study (by Robinson et al.) has finally looked at a question that we raised several years ago, which was what we could learn from the enormous amount of data available on the use of 5-ARIs in men being treated with these drugs for benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) associated with this non-cancerous condition. The full text of this article is available on line.

Robinson and his colleagues compiled data on the use of 5-ARIs by men in Sweden before a diagnosis of prostate cancer by using the National Prostate Cancer Register, the National Patient Register, and the Prescribed Drug Register, as well as the Swedish census. They then used these data to compare risk for prostate cancer between men who got a diagnosis of prostate cancer and “matched controls” who did not get prostate cancer over time. (A “matched control” is a man of similar characteristics to a diagnosed patient: similar age and health status, for a similar area of the country, etc. The nature of the Swedish health-care databases makes this particularly easy because every patient has a unique medical identification.)

Here are the core data from the study:

  • The researchers identified a total of 26,735 cases and 133,671 matched controls (after random selection of five matched controls in the background population for each men diagnosed with prostate cancer).
  • Men with lower-grade cancers tended to be younger than men with higher-grade cancers.
    • Men who had cancers with Gleason scores of 2 to 6 had an average (mean) age of 66.6 years.
    • Men who had cancers with Gleason scores of 7 had a mean age of 70.0 years.
    • Men who had cancers with Gleason scores of 8-10 had a mean age of 74.0 years.
  • More men in the case group than in the control group had undergone a biopsy before the date of their diagnostic biopsy.
    • 9.1 percent of men in the case group had had a biopsy before their diagnostic biopsy.
    • 2.5 percent of men in the control group had had a biopsy.
  • The case group included slightly higher proportions of married men, men with high education, and men with no co-morbidities than the control group.
  • In total, 7,815 men (1,499 cases and 6,316 controls) had received treatment with a 5-ARI.
  • 412 men had had been treated with a 5-ARI before the diagnosis of a cancer with a Gleason score of 8, 9, or 10.
  • Men on 5-ARI treatment for more than 3 years had an overall decrease in their risk for a diagnosis of prostate cancer (odds ratio [OR] = 0.72).
  • The same decrease in risk was evident for cancers with Gleason scores of 2 to 6 and Gleason scores of 7; however, …
  • There was no decrease in risk for cancers with Gleason scores of 8 to 10.
    • For men exposed to a 5-ARI for 0 to 1 years, OR = 0.96.
    • For men exposed to a 5-ARI for 1 to 2 years, OR = 1.07.
    • For men exposed to a 5-ARI for 2 to 3 years, OR = 0.96.
    • For men exposed to a 5-ARI for > 3 years, OR = 1.23.

Robinson et al. conclude that:

Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years’ treatment.

There are, of course, both strengths and limitations to a study of this type. For example, one of the limitations is that this is a retrospective, case-control analysis. On the other hand, one of the strengths is that this is a study with a large number of cases and controls and that it is based on data from “real world” patients and not just men eligible for entry into a pre-designed clinical trial.

It is certainly the case that this study supports the data published by Thompson and his colleagues in their re-analysis of data from the PCPT, in which they were able to show that there was no effect from the use of 5-ARIs on risk for prostate cancer mortality. It is also interesting to note that the overall reduction in risk for a diagnosis of prostate cancer in this study was about 28 percent (similar to that observed in the original PCPT).

Conversely, it also seems to be clear that, for those men who go on to develop high-grade prostate cancers with a Gleason score of 8 to 10, 5-ARI treatment has no preventive impact on the development of these types of aggressive cancers.

2 Responses

  1. For men exposed to a 5-ARI for > 3 years, OR = 1.23 for Gleason 8-10.

    As men are often on these drugs for many years, I fail to see how this can be construed as good news.

    Call me crazy.

    Doug

  2. Doug:

    In the PCPT study the fact that men had this type of small increase in risk for a diagnosis of Gleason 8 to 10 was not associated with any increase in risk of mortality at 15 years of follow-up. You need to look at what the two independent studies are saying together.

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