STATINS AND PROSTATE CANCER

If their findings are confirmed, statins could help patients avoid androgen deprivation therapy, the researchers said in a report published online April 26th in the Journal of Clinical Oncology.

Statins are known to have antiproliferative, proapoptotic, and radiosensitizing properties, according to senior author Dr. Stanley L. Liauw and colleagues at the University of Chicago.

Of 691 men with nonmetastatic prostate cancer treated at their hospital, 189 (27%) took statins either during or after curative-intent radiotherapy. The median follow-up period was 50 months.

The men who used statins had improved freedom from biochemical failure, defined as a prostate-specific antigen (PSA) level 2 ng/mL above the nadir.

At 4 years, the rate of freedom from biochemical failure was 93% in statin users and 80% in nonusers (p < 0.001). This outcome was better in statin users regardless of their risk status, their radiation dose, and whether or not they received androgen deprivation therapy.

Statin use also improved the rate of relapse-free survival (84% vs 69%, p < 0.001) and freedom from salvage androgen deprivation therapy (p = 0.0011).

In fact, the authors report, "the effect of (androgen deprivation therapy) was not as strong as that of statin use in any risk group."

On multivariable analysis, factors associated with freedom from biochemical failure were statin use (hazard ratio 0.43) and log PSA (HR 1.7). Factors associated with relapse-free survival were statin use (HR 0.57), Gleason score < 7 (HR 0.73), log PSA (HR 1.5) and radiotherapy dose > 74 Gy or brachytherapy (HR 0.75).

Statin use did not affect overall or cause-specific survival or freedom from distant metastases, however.

Most patients were taking atorvastatin (n = 96) or simvastatin (n = 49). Outcomes did not differ by choice of statin or by doses above or below 40 mg simvastatin equivalents.

Lower LDL cholesterol level was linked with improved freedom from biochemical failure. The authors point out that "cholesterol is a precursor for androgen formation, and it is conceivable that by lowering cholesterol levels, statins may lower levels of intraprostatic androgens."

Because of the observational nature of the study, the research team says that a randomized trial will be required to verify their findings.

In an editorial, Dr. Anthony V. D'Amico from Brigham and Women's Hospital, Boston, points out that statin users may be more health conscious or have increased access to care compared with nonusers. He recommends that future studies adjust for other known adverse prognostic factors, such as PSA velocity and advanced grade tumors, to make sure that findings can't be explained by an imbalance favoring statin users.

"Ultimately," Dr. D'Amico says, "a prospective randomized trial is needed to assure that selection bias does not exist to properly evaluate whether statin use reduces the risk of PSA recurrence and prostate cancer specific mortality in men undergoing radiation therapy with or without hormone therapy."

J Clin Oncol 2010.