Statin therapy appears to extend progression-free survival for men on ADT


A combination of two studies by a group of researchers at the Dana-Farber Cancer Institute in Boston has provided some further evidence of the potential benefits of statin therapy for men being treated with androgen deprivation therapy (ADT) … but the evidence is preliminary and needs validation.

According to an article by Harshman et al., published today in JAMA Oncology, along with a media release from the Dana-Farber Cancer Institute, men who are taking a statin at the time they start ADT, and who continue with statin therapy during the course of their ADT, had a significantly longer time to biochemical progression than men who were not taking a statin.

These data come from a retrospective analysis of data from 926 patients treated with ADT at Dana-Farber, of whom 238 (31 percent) were receiving a statin at the time of initiation of ADT.

The core study findings are as follows:

  • Median patient follow-up was 5.8 years.
  • 644/926 patients (70 percent) exhibited disease progression while receiving ADT.
  • Median times to disease progression (TTP) during ADT were
    • 20.3 months for all 926 patients
    • 27.5 months for men taking statins
    • 17.4 months for men not taking statins
  • This association between statin use and TTP was statistically significant, and remained remained statistically significant after adjustment for predefined prognostic factors (adjusted hazard ratio [aHR] = 0.83; P = 0.04).
  • The positive statin effect was observed for
    • Patients with evident metastasis (aHR= 0.84)
    • Patients with no evidence of metastasis (aHR = 0.79)
  • Laboratory data also confirmed that statin use helped to block uptake of dehydroepiandrosterone sulfate (DHEAS).

This finding is clearly important, but it really only adds to the pressure to conduct randomized trials of the use of statins in the management of prostate cancer. We have seen before that associations like this, based on retrospective analyses of data that were never collected to examine such an effect, can out to be misleading and potentially dangerous. If we want to know that this potential utility of  a statin is “real”, what we need is an randomized, double-blind trial in about 500 men who are randomized to statin or non-statin therapy at the time of initiation of a uniform type of ADT.

 

6 Responses

  1. Do we know if they were on CHT vs IHT? And what type of ADT?

  2. It appears that they were all on continuous ADT … but it is not clear exactly what type, and I suspect that that may have varied over time.

  3. It does appear that the authors looked at whether delayed biochemical progression in men who received a statin meant improved quality of life or increased survival time.

  4. Strikingly short progression-free periods -– explanation: metastasis at start of ADT for majority of patients in the study

    As a veteran of 14 years of successful IADT for a challenging case, I was struck by the remarkably short success spans before disease progression for ADT treatment in this study: a median of just 20.3 months for all 926 patients, with slightly over a 10-month advantage for men taking statins compared to those not taking statins, but a median progression-free span of just 27.5 months even for those on statins. That’s an impressive difference from the viewpoint of statin use, but not so hot for those of us hoping for long-term success with ADT. (As the paper states, “Progression was defined as a minimum of 2 increases in PSA level.”)

    It was clear that some of the patients in this study group were metastatic, and a high proportion of metastatic patients could explain the relatively short median success spans for ADT, as ADT is well known to be a lot less successful in men who are already metastatic, especially if mets are widespread. (Of course, the study was done with older drugs, not the new power-house agents like abiraterone, Xytiga, and Firmagon, with other newer drugs in support; those should make a difference in ADT treatment for men with metastatic disease, and then there are other drugs like Xofigo, Provenge, etc. that are now in the arsenal of treatments.)

    That heavy proportion of men with metastatic disease at the start of ADT turns out to be the case, and that explains the short “median” success spans for ADT. As the study states in Table 1, 60% had metastases at the time ADT was initiated. As it takes just 50% of members of a study to establish a median value (half of all members above a value, half below), it turned out that a strong majority of those progressing were men who were already metastatic when they started ADT. Figure 3 in the complete paper displays results for the non-metastatic and metastatic patients. Median time of successful ADT in the non-metastatic group was about 3 years for non-statin users and about 4 years for statin users, in contrast to corresponding figures for metastatic men of about 1 year and 1.5 years.

    Regarding type of ADT, the paper tells us that 71% were also on an antiandrogen, but just 4% were on a 5-alpha reductase inhibitor (Table 1).

  5. Jim,

    The short progression-free time was what I noticed as well. I’m a rookie IHT guy at 5.5 years and it took a veteran of 14 years to clear that up for me. … Thanks.

    Was there any information about the type of statin or the dose taken?

  6. The above summary completely fails to mention what for me is the most interesting part of this paper: a proposed biological mechanism for the effect of statins on progression, and in vitro studies that provide support for this mechanism.

    Briefly, the authors propose that statins competitively inhibit uptake of DHEAS into cancer cells by binding to a molecular transporter called SLCO2B1, which transports both statins and DHEAS into the cell. DHEAS is an androgen precursor which continues to be produced by the adrenal glands even when on ADT. Thus, the presence of a statin in the extracellular environment could plausibly slow progression in any prostate cancer cells that are able to convert DHEAS to dihydrotestosterone.

    Figure 1 in the paper shows the relative effect of four different statins in two prostate cancer cell lines in this in vitro study. As noted, this paper is available for free (and, with free registration, can be downloaded in PDF form).

    As theoretical work, I find this really interesting. But, as sitemaster rightly points out, the clinical implications of this work are far from clear, and attempts to draw clinical implications in the absence of good clinical studies can be misleading and potentially dangerous.

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