5-ARIs and risk for high-grade prostate cancer: yet another data set


The question of whether the use of 5α-reductase inhibitors (5-ARIs) like finasteride (Proscar) and dutasteride (Avodart) is really associated with a significantly increased risk for diagnosis of high-risk and/or lethal prostate cancers remains unanswered. However, yet another set of data from the Health Professionals Follow-up Study (HPFS) has offered us some additional insights.

As The “New” Prostate Cancer InfoLink has observed on a number of prior occasions, if the use of  5-ARIs really is associated with a significant increase in the likelihood of a diagnosis of high-risk and/or lethal prostate cancers, then wouldn’t this risk be apparent among the tens of thousands of men who have been getting treatment (often for years) with 5-ARIs for benign prostatic hyperplasia (BPH) — the very common enlargement of the prostate that occurs with increasing age?

The HPFS research team (see Preston et al.) therefore looked at their data on 38,058 men who had been followed from 1996 to 2010, and specifically at data from those men who had been diagnosed with prostate cancer during that timeframe and the use of 5-ARIs by these men during that same timeframe.

Here is what they found:

  • 3,681 cases of incident prostate cancer were identified among 448,803 person-years of follow-up.
    • 289 cases were “lethal” (i.e., metastatic disease or actual death from prostate cancer).
    • 456 cases were high grade (i.e., a Gleason score of 8 to 10 at diagnosis).
    • 1,238 were intermediate grade (i.e., a Gleason score of 7).
    • 1,600 were low grade (i.e., a Gleason score of 2 to 6).
  • 2,878/38,058 men (7.6 percent) said they had used a 5-ARI between 1996 and 2010.
  • After making appropriate adjustments for things like age, PSA testing, and other confounding factors, it was shown that, during the study period, compared to non-users of 5-ARIs who were diagnosed with prostate cancer,
    • 5-ARI users had a significantly lower overall risk for diagnosis of prostate cancer (hazard ratio [HR] = 0.77).
    • 5-ARI users had a significantly lower risk for diagnosis with Gleason 7 disease (HR = 0.67).
    • 5-ARI users had a significantly lower risk for diagnosis with low-grade (i.e., Gleason 2 to 6) prostate cancer (HR = 0.74)
    • 5-ARI users had a comparable risk for diagnosis with high-grade (i.e., Gleason 8 to 10) prostate cancer (HR = 0.97)
    • 5-ARI users had a comparable risk for diagnosis with lethal prostate cancer (HR = 0.99).
  • Increased duration of use of 5-ARIs was associated with
    • A lower overall risk for diagnosis of prostate cancer (HR for 1 year of additional use =0.95)
    • A lower overall risk for diagnosis of localized prostate cancer (HR for 1 year of additional use =0.95)
    • A lower overall risk for diagnosis of low-grade (i.e., Gleason 2 to 6) prostate cancer (HR for 1 year of additional use =0.92)
    • No increase in risk for lethal, high-grade, or Gleason 7 prostate cancer.

The authors conclude that:

While 5-ARI use was not associated with developing high-grade or lethal prostate cancer, it was associated with a reduction in low-grade, GS 7, and overall prostate cancer.

However, they appropriately note also that

Because the number of patients with high-grade or lethal prostate cancer in our cohort was limited, we cannot rule out potential risk of harm with 5-ARI use.

While these data can not be used to make an absolute statement that there is no association between the use of 5-ARIs and risk for high-grade or lethal prostate cancers, they do add to the data suggesting that such risk, if it does exist, is extremely small.

What would, of course, be extremely helpful would be an analysis by the HPFS research team of all men in their database who took 5-ARIs during the study period and the occurrence of prostate cancer among this cohort, compared to the occurrence of prostate cancer in those who did not take a 5-ARI. Whether funding exists to examine that question, we do not know.

4 Responses

  1. Thanks. A little more assurance is always good. After 5 years of taking finasteride, my PSA continues to go down and BPH issues mostly resolved. Now if only more positive studies about inflammation and development of prostate cancer. I will continue to ignore the USPTF recommendations for PSA screening and colon cancer screening as more evidence is developed in favor of such screenings, even for people older than 75.

  2. Obviously a report which I find supportive to my long-known personal opinion of the importance of 5AR inhibitors (preferably dutasteride/Avodart) as that third medication along with an LHRH agonist/antagonist and antiandrogen for those men moved to androgen deprivation therapy (ADT) as their primary treatment.

  3. An important tool to prevent prostate cancer. Highly recommended while on active surveillance. Shown not to cause high-grade disease. When will 5-ARIs will be accepted? Not any time soon …

  4. Yes, it’s in line with what a lot of us have thought for years, and kudos to the researchers for touching this base. While this is what I would have predicted, it is still reassuring to me as I have now been on a 5-ARI drug continuously since September 2000 as part of my arsenal to battle a challenging case of prostate cancer, now possibly cured with 39 sessions of TomoTherapy IMRT last year supported by a fourth round, 18 months of ADT. I’m staying on Avodart at present — kind of as a safety net or security blanket.

    I watched live video of the whole FDA hearing on 5-ARIs for prostate cancer, back in December of 2010 off the top of my head. There was a lot of support for 5-ARIs and clear explanation of the research data, but Dr. Patrick Walsh, a long-time opponent of 5-ARI use but with apparently no experience using them in his own practice, buffaloed and hustled the advisory committee into taking a negative view.

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