Statins may reduce prostate cancer deaths

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Findings may prompt more statin use

The findings by Dr. Yu and her colleagues add important new information supporting a link between statin use and a lower risk of prostate cancer–related mortality.

While similar associations were seen in a 2012 meta-analysis and in five subsequent epidemiologic studies, the current findings nicely illustrate the need to identify the specific window of timing for the effects of a chemopreventive agent. Attention to timing of an exposure may help resolve apparent discrepancies across epidemiologic studies and is essential in guiding the design of randomized trials.

But where do the findings lead at this point?

A randomized primary prevention trial seems unlikely because of the need to test statin use prior to diagnosis, and because such a trial would have to be large and lengthy – and thus may not be feasible. On the other hand, a pre-prostatectomy, neoadjuvant study of men undergoing surgery could be useful for elucidating the molecular mechanisms of statins on the local tumor environment.

Administrative medical databases with linkage to long-term outcomes might also help.

Meanwhile, as we wait, the current data may be sufficient to sway some clinical decisions toward statin use for men who are on the borderline for cardiovascular disease prevention.

Lorelei A. Mucci, Ph.D., and Dr. Meir J. Stampfer are with the Harvard School of Public Health in Boston. They made their remarks in an editorial that accompanied Dr. Yu’s study (J. Clin. Oncol. 2014;32: 1-2). Both reported having no disclosures.



The use of statins following a prostate cancer diagnosis was associated with a decrease in all-cause and prostate cancer–related mortality risks in a large cohort of men from the United Kingdom.

The risk reduction was greatest among those who also used statins prior to their diagnosis, said Dr. Oriana Yu, of Jewish General Hospital, Montreal, and her colleagues.

The findings support experimental evidence suggesting a possible antitumor effect of statins on prostate carcinogenesis. Additional observational studies are needed to confirm the findings before a randomized controlled trial is launched to assess the effects of statins in the adjuvant setting, they said.

The study subjects were 11,722 men (mean age, 71.3 years) who were retrospectively identified from a large population-based electronic database. All were newly diagnosed as having nonmetastatic prostate cancer between April 1, 1998, and Dec. 31, 2009. During a mean follow-up of 4.4 years, 3,499 died, including 1,791 who died from prostate cancer.

Those who used statins after their prostate cancer diagnosis had a 24% decrease in the risk of prostate cancer mortality (hazard ratio, 0.76), and a 14% decrease in the risk of all-cause mortality (HR, 0.86). Statin use post diagnosis also was associated with a decreased risk of distant metastasis (HR, 0.77).

Among those who also used statins prior to their diagnosis, the corresponding hazard ratios for prostate cancer–related and all-cause mortalities were 0.55 and 0.66, compared with 0.82 and 0.91, respectively, for those who only used statins after diagnosis, the researchers reported (J. Clin Oncol. 2014; 32:5-11).

"A dose-response relationship was observed in terms of cumulative duration of use and dose, with the HRs becoming progressively more protective with longer durations of use and higher cumulative doses," they wrote.

For example, the adjusted hazard ratios for those using statins for less than 1 year and for those using statins for 3 or more years were 0.99 and 0.61, respectively. The adjusted hazard ratios for cumulative doses of less than 365 mg and 1,096 mg or more were 0.84 and 0.57, respectively.

Accumulating evidence suggests that statins have antitumor effects. Observational studies have looked at the association between statin use and prostate cancer outcomes, but the findings have been inconsistent, and none have specifically assessed whether prediagnosis use of statins modified the association seen between postdiagnosis use and outcomes, the investigators said.

The findings of an effect modification by prediagnostic use of statins in this study could be explained by several factors.

• Tumor characteristics may be more favorable in those using statins before diagnosis, resulting in improved prostate cancer outcomes, the investigators said. In the current study, however, those using statins before diagnosis were slightly more likely to have higher Gleason scores compared with nonusers.

• Duration of statin use is longest among those who used statins before their diagnosis, as in this study.

• Men who start statins before their prostate cancer diagnosis may differ from those who start after diagnosis. "Specifically, it is possible that the latter group required statins as a consequence of certain treatment, such as androgen deprivation therapy, which is known to increase lipid levels," and typically is prescribed to those with advanced prostate cancer, which would make statins seem to have more modest effects.

This study was supported by the Canadian Institutes of Health Research. Dr. Yu reported having no disclosures. One of her coauthors, Samy Suissa, Ph.D., reported serving as a consultant or adviser for AstraZeneca, Boehringer Ingelheim, and other companies.

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