Philadelphia—Extending life is the greatest challenge with prostate-cancer patients who have a high PSA and Gleason scores of 8 or more.

Two commonly prescribed medications—cholesterol-lowering statins and the diabetes therapy metformin—have shown promise as having anticancer effects, according to a report in Cancer Medicine, but it remained unclear which of the two, often prescribed together, contributes the most and whether they can extended survival in high-risk prostate cancer.

Thomas Jefferson University researchers now can report that statins, alone or with metformin, increase survival in men with hard-to-treat prostate cancer.

“Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately,” explained senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center—Jefferson Health.

The study team notes that preclinical studies suggested that metformin and statins may delay prostate-cancer metastases but that data in humans were limited. “To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high-risk PCa,” the authors write.

To do that, researchers conducted a population-based retrospective cohort study identifying patients from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database. The Medicare Prescription Drug Event files were used to document use of metformin and statins by 12,700 patients with high-risk PCa.

Results indicated that statins alone or in combination with metformin were significantly associated with reduced all-cause mortality (hazard ratio [HR]: 0.89; 95% CI, 0.83-0.96; and HR: 0.75; 95% CI, 0.67-0.83, respectively) and PCa mortality (HR: 0.80; 95% CI, 0.69-0.92) and 0.64; 95% CI,  0.51-0.81, respectively.

“The effects were more pronounced in post-diagnostic users: combination use of metformin/statins was associated with a 32% reduction in all-cause mortality (95% CI, 0.57-0.80), and 54% reduction in PCa mortality (95% CI, 0.30-0.69),” the study found.

Yet no significant association of metformin alone was observed with either all-cause mortality or PCa mortality, the researchers write.

“With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone,” explained Dr. Lu-Yao. “Those taking metformin alone were relatively rare, and there was no significant association with all-cause mortality.”

Men using atorvastatin, pravastatin, or rosuvastatin—but not lovastatin—had a reduction in mortality compared with nonusers, according to the study, which points out that those results were consistent with a recent population-based cohort study using Taiwan National Health Insurance Research Data.

Of the three statins studied, men on atorvastatin also had longer median time to progression on androgen-deprivation therapy compared with those who were not treated with statins. “Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits a potent lipid-lowering effect per dose of any statin, and has the greatest bioavailability and one of the longest half-lives,” Dr. Lu-Yao emphasized, adding, “Our study showed that the effects were more pronounced in patients taking statins after the diagnosis of prostate cancer, 54% reduction in PCA mortality among patients with high-risk prostate cancer.”

In fact, researchers determined that the magnitude of reduction is comparable to the results of men treated with androgen-signaling inhibitors.

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