The short-term, potential future of prostate cancer prevention

A recent article in the Journal of General Internal Medicine argues that using 5α-reductase (5-ARI) therapy (i.e., with dutasteride or finasteride) to prevent the early onset of prostate cancer is not justified by the available data. … And we entirely agree, when the argument is based on the premise that such preventive therapy should not be used in a widespread manner by the primary care community.

Hoffman et al. have put forward a strong and coherent recommendation, based on the acknowledged facts that:

  • Data from the PCPT and REDUCE trials show a limited benefit from 5-ARI therapy (a roughly 25 percent reduction in risk of diagnosis over about 4 years).
  • There was a small but increased risk for diagnosis of Gleason 8-10 prostate cancer in men on 5-ARI therapy.
  • Long-term follow-up data are not available
  • Most of the benefit shown for preventive use of 5-ARI therapy appears to have been confined to low-risk patients identified through regular testing (“screening”) for prostate cancer — which has itself yet to be clearly associated with a mortality benefit in the US.

There is no doubt at all in our minds that the use of 5-ARIs by the primary care community as agents for the widespread prevention of prostate cancer would be highly inappropriate based on these currently available data.

We are already over-treating low-risk prostate cancer (just as we are probably over-treating a whole bunch of other conditions — in children and in adults).

Some would argue that we are also over-diagnosing prostate cancer (and other disorders). A different way to think about this, however, is to acknowledge that — as a society — we have limited ability to recognize and appreciate that having a diagnosis of some type does not and should not necessarily mean it needs to be treated. There are excellent examples of “conditions” that we do not treat, such as monoclonal gammopathy of undetermined significance (MGUS), which is a potential precursor to multiple myeloma, but which is never treated, just monitored. The increasing acceptance and application of active surveillance in the management of low-risk prostate cancer has been a major step forward, and we expect the use of active surveillance to increase over the next decade.

However, the question that we believe is still unanswered is whether there is a subset of men at high risk for prostate cancer who do get a very real benefit from the potential of 5-ARIs to delay a diagnosis of prostate cancer. This subset would potentially include — at a minimum — men of African American ethnicity and other men with a clear family history of progressive prostate cancer. And we would strongly suggest that the preventive use of 5-ARIs in such patients should normally be carried out by experienced urologists and oncologists rather than by members the of the primary care community.

We are also well aware of a subset of men in whom fear of a diagnosis of prostate cancer is a highly debilitating effect. This is probably a very small number of men compared to the population as a whole, but one is again tempted to wonder whether such men would actually benefit from chemoprevention with a 5-ARI.

For a variety of reasons, it is likely that we will never see a trial of another 5-ARI to prevent prostate cancer in high-risk patients. Indeed, as we have said previously, one of the consequences of the recent decision not to approve dutasteride as a chemopreventive agent for prostate cancer is likely to be abandonment by the biopharmaceutical industry of further attempts to seek FDA approval for chemopreventive agents. The cost is too high and the probability of success too low.

The good news, of course, is that apparently drinking pomegranate juice or taking pomegrante extract tablets really does appear to delay the diagnosis and the progression of low-risk prostate cancer — just like the 5-ARIs — with no clinically significant side effects at all. Perhaps the primary care community will feel that this is a more acceptable strategy. Of course it’s a strategy that can’t be supported with a prescription … but maybe that’s a good thing. The individual who believes he is at risk will be able to make his own decision and pay for it without needing that decision to be formally “authorized” by a physician and an insurance company. Certainly for all those men over 40 who are passionately in favor of repeal of the Patient Protection and Affordable Care Act, a daily dose of pomegranate juice or extract would appear to be a defining opportunity in the future of American health care.

2 Responses

  1. I was wondering whether the drug companies would abandon studying chemoproventive drugs like dutasteride if they knew they had a market of just African Americans?

  2. Robert:

    I really don’t think that is the issue. Drugs have been developed in the past specifically for African American target audiences.

    The problem has much more to do with the fact that the Food & Drug Administration (for many good reasons) is highly unwilling to approve chemopreventive agents if there is any possibility of a signal that use of the drugs in question might induce additional problems. However, since one has to carry out very large trials over a significant period of time to demonstrate a chemopreventive effect, there is a significant possibility that such complications may occur in a very small number of people. From a drug company’s point of view, one has to ask whether the cost of doing such trials is worth it if there is only a very low likelihood of getting a drug approved for a chemo preventive indication — regardless of the ethnicity or socioeconomic status of the target audience.

    About 20 years ago, Merck developed a drug called ivermectin which could be used to treat and prevent a parasitic disease called onchoceriasis, which is common in West Africa. I can’t believe they made any money at all on developing this drug for onchoceriasis, but they probably learned a great deal scientifically, and they certainly did make money selling this drug to dog owners in the developed world to prevent a canine parasitic infection known as heartworm.

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