Statins in the prevention and management of prostate cancer: an update

A recent review article in the journal Nature Reviews: Urology has concluded that, while we are learning a lot more about the potential role(s) of statins in the prevention and management of prostate cancer, we still have no definitive evidence of their value.

Statins are drugs like simvastatin (Zocor), pravastatin (Pravachol), atorvastatin (Lipitor), and (rosuvastatin) Crestor, that are very widely used by primary care physicians and others in the management of elevated cholesterol levels. In the past decade or so, we have also learned how important cholesterol levels can be in helping to “feed” the biochemical pathways leading to elevated levels of secondary hormones that can be converted to dihydrotestosterone — a key metabolite in the development and progression of prostate cancer.

However, what has not been shown yet, in any large, definitive, prospective, randomized clinical trial is:

  • Whether treatment with a statin can actually reduce risk for diagnosis with prostate cancer (and most especially risk for diagnosis with clinically significant prostate cancer)
  • Whether treatment with a statin (in combination with other forms of therapy) can actually delay progression of higher-risk and/or more advanced forms of prostate cancer.
  • Whether treatment with a statin (in combination with other forms of therapy) can improve either prostate cancer-specific or overall survival in men diagnosed with prostate cancer

In their recent review, Alfaqih et al. make a series of key points about what we currently do and do not know:

  • The use of statins appears to be associated with improved prostate cancer-specific survival, most particularly in men who receive radiation therapy as a form of first-line treatment
  • Pre-clinical, laboratory studies have shown that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models.
  • The apparent effects of statins in men with prostate cancer could possibly be caused by one or more of several cholesterol-mediated and non-cholesterol-mediated mechanisms that affect pathways essential for cancer formation and progression.
  • “Sufficient data are lacking to support the use of statins for the primary prevention of prostate cancer”.
  • “Secondary and tertiary prevention trials in men who have been diagnosed with prostate cancer might soon be performed.”

At this time there are only a small number of ongoing, prospective clinical trials designed to test whether statins have an effect in the management of prostate cancer:

  • In Toronto, the LIGAND trial is a randomized, Phase II trial designed to test whether the combination of metformin and atorvastatin may be able to delay the need for androgen deprivation therapy (ADT) in men who have a rising PSA after inital treatment for prostate cancer with surgery and/or radiation therapy.
  • Also in Toronto, another very small trial is testing whether treatment of higher-risk patients with a combination of a statin (Lescor) + pimonidazole prior to surgery for their prostate cancer might affect their risk for progression post-surgery.
  • In New Jersey and Michigan, an even smaller trial has been in progress for 6 years to test whether treating men with a combination of atorvastatin + celecoxib (Celebrex) may be able to actually stop any progression of prostate cancer in men originally7 diagnosed with localized prostate cancer who have a rising PSA after definitive local therapy with either surgery or radiation therapy.

We are going to need much larger trials than these if we are ever going to actually prove that the use of statins can significantly impact the risk for diagnosis with prostate cancer or the risk for progression after a diagnosis of prostate cancer in well-defined groups of patients.

3 Responses

  1. The downside is limited from taking both metformin and a statin — for most people reported co-morbidities are minimal. Anecdotally, I know many men with more advanced disease who have decided to err on the side of caution and use both drugs — if they can get them prescribed.

  2. A minor correction: the drugs being administered in the “very small trial” you refer to are Lescol (a statin) and pimonidazole (a hypoxia marker).

  3. Thank you Tom … duly corrected above.

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