Should all patients starting on ADT be on a statin too?

A newly published article in JAMA Oncology has now suggested that adding a statin to a patient’s treatment regimen at initiation of androgen deprivation therapy (ADT) may significantly impact time to disease progression among men diagnosed with progressive, hormone-sensitive prostate cancer. This new paper by Harshman et al. is available on line as a full text article.

We should be very clear up front that the authors’ suggestion is based on a combination of laboratory data and a retrospective analysis of data from a relatively large patient cohort, but it is not based on any type of prospective clinical trial, and so no one is actually recommending that all men starting on ADT should also be started on a statin (yet).

Harshman et al. did two things:

  • They carried out laboratory studies to demonstrate that the use of statins can interfere with the uptake of dehydroepiandrosterone sulfate (DHEAS) — a known precursor of testosterone. (And they had previously shown that DHEAS is a substrate for another molecule called SLCO2B1, and that statins use SLCO2B1 to enter cells.)
  • They looked back through the available data on the cohort of 900+ patients treated with ADT through the Dana-Farber Cancer Institute in Boston to assess how many of those patients were on statin therapy at the time of initiation of ADT and whether being on a statin appeared to affect patient outcomes over time.

With respect to the second part of the study, here is what they found:

  • 283/926 patients in their ADT cohort (31 percent) were taking a statin at the time of initiation of ADT.
  • Average (median) follow-up was 5.8 years.
  • During the follow-up period, 644/926 patients (70 percent) exhibited disease progression while receiving ADT.
  • Average (median) time to disease progression (TTP) while on ADT was 20.3 months.
    • For men on statin therapy at initiation of ADT, median TTP was 27.5 months.
    • For men not taking a statin at initiation of ADT, median TTP was 17.4 months
    • This difference was statistically significant (P < 0.001).
    • The association was still statistically significant after adjusting for predefined prognostic factors (adjusted hazard ratio [aHR] = 0.83; P  = 0.04).
  • The positive effect of being on a statin was observed for patients with and without metastases.
    • For M0 patients, aHR = 0.79.
    • For M1 patients , aHR = 0.84.

The authors conclude that, in this study:

Statin use at the time of ADT initiation was associated with a significantly longer TTP during ADT even after adjustment for known prognostic factors. Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.

There is an increasing amount of evidence that statin therapy may be beneficial in at least some men with prostate cancer, and in particular among men being treated with ADT for progressive and advanced forms of prostate cancer. According to Harshman et al. there are currently some 10 prospective trials ongoing or maturing that should help us to further understand the potential role(s) for statin use in the management of prostate cancer.

On the up-side, what we do know is that statins have a well-established and well-understood safety profile and that they have other benefits already for many older men because of their effects as cholesterol-lowering agents (and their consequent impact on cadriovascular disorders). However, if we can prove through randomized, prospective clinical trials that statin therapy also extends time to disease progression (and possibly survival too) for men with progressive forms of prostate cancer, this may be a considerable step forward.

3 Responses

  1. Do we know if these men were on CHT or IHT?

    Do we know the type and dose of statins? Probably all over the map.

    Years ago I had moderately high cholesterol and was put on a statin. Despite my very good cholesterol numbers I stay on a statin because of the possible benefits for prostate cancer. I’ve taken a statin for all the time I was on hormone therapy and for the last 33 months that I’ve been on a hormone therapy vacation.

    Oddly, and I’m sure it’s just a coincidence, my PSA became detectable just recently when I switched from simvastatin to rosuvastatin (Crestor).

  2. Jerry:

    As far as I can tell, at a quick glance, the actual paper gives no detailed information at all about the types of ADT or the types of statins being used by the patients. However, my guess would be that the majority of these men would have been on continuous as opposed to intermittent ADT.

  3. In my experience as a patient and a prescriber, statins are not totally benign drugs. I was personally able to achieve an elevated CK level along with muscle cramps while taking a statin when my cholesterol rose courtesy of ADT. Switching to a different statin seemed to take care of that problem. My fear is that they might now be prescribed by physicians who wish to take advantage of a theoretical benefit, but who are not familiar with the need to monitor patients for real adverse effects.

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