Statins during RT may lower risk of prostate ca relapse

LOS ANGELES-Men who have undergone high-dose radiation therapy for prostate cancer have a reduced risk of relapse if they were taking statins during their radiation therapy, finds a retrospective study reported at the 2007 ASTRO annual meeting (abstract 203). The benefit was greatest among those men with high-risk disease.

"There are some studies that have shown or suggested that statins may interfere with antiapoptotic pathways and may, in fact, act as radiation sensitizers in experimental tumor models," said senior author Michael J. Zelefsky, MD, of Memorial Sloan-Kettering Cancer Center.

The researchers assessed associations between use of statins during high-dose 3D conformal/intensity-modulated radiation therapy (75.6 to 86.4 Gy) and various outcomes among 871 men with clinical stage T1c to T3 prostate cancer treated between 1994 and 2000 at the center.

Nineteen percent of the patients were taking a statin at the time of diagnosis and continued to do so during radiation therapy, Dr. Zelefsky said. Some 29% had favorable-risk disease, 46% had intermediate-risk disease, and 25% had high-risk disease. About half (54%) were treated with neoadjuvant hormonal therapy.

Improved relapse-free survival

With a median follow-up of 7 years, the 10-year estimated probability of survival free of a PSA relapse was significantly higher among the statin users than among the nonusers overall (76% vs 66%), Dr. Zelefsky said.

By risk category, the difference was marginal among the intermediate-risk group (P = .07) and significant among the high-risk group (P = .005).

In a multivariable analysis, the likelihood of biochemical control was nearly doubled in the intermediate-risk group and more than tripled in the high-risk group with statin use (see Table).

Statin use was also associated with a higher estimated probability of distant-metastases-free survival in the high-risk group (P = .04), Dr. Zelefsky said. In a multivariable analysis, statin use conferred a significant tripling of the likelihood of distant control in this group (HR 3.07). However, neither overall survival nor cause-specific survival was significantly affected by statin use.

Study limitations

"Clearly, because of the inherent limitations of such a study, we would recognize that only a prospective randomized trial would be able to confirm these findings," Dr. Zelefsky said. "We cannot really comment with confidence regarding the optimal statin dose, the optimal duration of a statin, and which particular statin would confer the greatest benefit for patients who are treated with radiotherapy."

Dr. Zelefsky agreed with an attendee who questioned whether statins may somehow interact with androgen suppression, thereby explaining the greater benefit among men at high risk, about 75% of whom received this therapy. "As part of a trial, it would be interesting to explore the use of statins in conjunction with hormonal therapy and in isolation of hormonal therapy," he said.