August 22, 2017
In men who took a statin after they were diagnosed with prostate cancer, cancer-specific and overall mortality rates were lower than in men who did not take a statin, a nationwide Danish registry study has found.
"Increasing evidence indicates that the use of statins may delay prostate cancer (PC) progression," write the authors, led by Signe Benzon Larsen, PhD, Danish Cancer Society Research Center, Copenhagen, Denmark.
"Our study adds to the increasing evidence that statin use is associated with reduced PC mortality," the investigators add.
The study was published online August 14 in the Journal of Clinical Oncology.
Dr Larsen and colleagues carried out a nationwide study of Danish men aged 35 to 85 years who had been diagnosed with prostate cancer from 1998 to 2011. The final cohort consisted of 31,790 men whose median age at the time of diagnosis was 70 years. The patients had either localized or advanced prostate cancer.
During a median follow-up of 2.8 years, 23% of the cohort died of prostate cancer; 37% died of another cause.
Slightly more than one fifth of the cohort (21%) took a statin during the first year after their diagnosis. This percentage ranged from a low of 4% among men who were diagnosed with prostate cancer from 1998 to 2001 to a high of 29% among men who received the same diagnosis from 2007 to 2011.
"Among postdiagnosis statin users, we observed a 17% reduction in PC mortality and a 19% reduction in mortality from all causes," the researchers report.
Two sensitivity analyses in which statin use was determined on the basis of patients filling two or more prescriptions for a statin either 1 year or 5 years after their diagnosis yielded comparable results, they add.
Results were similar when investigators assessed both cancer-specific and all-cause mortality among men who continued to take a statin after their diagnosis, as well as those who used a statin for the first time after receiving their diagnosis.
The investigators found that neither the dose or type of statin used, nor the clinical stage of disease, Gleason score, or use of a statin prior to the diagnosis of prostate cancer had a discernible effect on mortality rates.
The investigators point out that during the study period, 23% of the cohort died of prostate cancer and that overall survival of men with the malignancy was "markedly lower" in Denmark than in other Scandinavian countries.
This might be explained by the fact that prostate-specific antigen testing is used less often in Denmark than in other Nordic countries and that as a consequence, men tend to present with more advanced disease, they comment.
Other Studies With Similar Findings
A number of epidemiologic studies indicate that the use of statins following a diagnosis of prostate cancer is beneficial. However, some studies have suggested that the benefit is greater among men who were taking a statin before being diagnosed with prostate cancer, note experts in an accompanying editorial.
Editorialists Lorelei Mucci, MPH, from the Harvard T. H. Chan School of Public Health, Boston, Massachusetts, and Philip Kantoff, MD, from the Memorial Sloan Kettering Cancer Center, in New York City, comment:
"If we believe the finding is causal, the next question is whether there is sufficient evidence to recommend prescribing a statin for men who are diagnosed with prostate cancer and, if not, what additional evidence is needed to translate the findings clinically."
The editorialists indicate that a proof-of-concept trial is needed before physicians start routinely prescribing a statin for men with prostate cancer. "At the least, we believe that clinicians can assure patient who are taking statins that they can continue their use during prostate cancer care, as there is no evidence of harm reported by epidemiologic studies," they write.
Bias in Studies?
However, a group of investigators suggests that the reductions in mortality that have been reported in various observational studies may be the result of selection bias and other biases.
Writing in an article published online August 20 in JAMA Oncology, Louise Emilsson, MD, PhD, Harvard T. H. Chan School of Public Health in Boston, and multicenter colleagues argue that after different kinds of biases are taken into consideration, observational studies that show a survival advantage among statin users with different kinds of cancers no longer demonstrate any advantage of statin therapy.
Dr Emilsson and colleagues examined data on 17,372 patients with cancer from the Surveillance, Epidemiology and End Results–Medicare database from 2007 to 2009. They found that initiating statin therapy within 6 months of a patient's receiving a diagnosis of colorectal, breast, prostate, or bladder cancer had little or no effect on either cancer-specific or overall mortality during a 3-year follow-up period when corrected for selection and "immortal-time" bias. Immortal-time bias was defined as patients using a statin and surviving during at least part of the follow-up period.
"When applying a methodological approach that minimizes immortal-time and selection bias, we found no suggestion that initiation of statin therapy after cancer diagnosis improves the early survival in patients with stages I through III cancer," the team concludes.
"In an analysis that was susceptible to neither selection bias nor immortal-time bias, the HRs [hazard ratios] were essentially null," they add.
Dr Larsen has received travel and accommodation expenses from Janssen Oncology. Dr Mucci has received research funding from Astellas, Medivation, Sanofi, and Bayer. Dr Kantoff has numerous financial relationships with industry, as noted in the original article. Dr Emilsson has disclosed no relevant financial relationships.