Use of statins and prostate cancer recurrence among patients treated with radical prostatectomy
Version of Record online: 25 APR 2013
© 2013 BJU International
Volume 111, Issue 6, pages 854–856, May 2013
How to Cite
Kirby, M. (2013), Use of statins and prostate cancer recurrence among patients treated with radical prostatectomy. BJU International, 111: 854–856. doi: 10.1111/j.1464-410X.2012.11722.x
- Issue online: 25 APR 2013
- Version of Record online: 25 APR 2013
Prostate cancer is the most commonly diagnosed malignancy and one of the leading causes of cancer mortality in the western world . The prospect that statins may reduce the risk of cancer and cancer recurrence is intriguing. Statins may have the ability to inhibit tumour cell proliferation and induce apoptosis . There are also potential benefits regarding anti-angiogenic, anti-inflammatory, and anti-invasive properties which may affect tumour cell viability and metastatic potential [3, 4].
A recent study looked at statins and the risk of cancer after heart transplantation . The cumulative incidence of tumours 8 years after transplantation was reduced in patients receiving statins (34 vs 13%; P < 0.003) and statin use was associated with improved cancer-free and overall survival (P < 0.001). Statins reduced the risk of occurrence of any malignancy by 67%, but it was impossible to adjust for all potential confounders because of the very long follow-up period (1985–2007).
A recent comprehensive review of statin use and cancer risk concluded that there were few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed . Data on the positive effects of statins on cancer prognosis in secondary prevention were lacking, with the exception of consistent evidence that statins are associated with a reduced risk of advanced/aggressive prostate cancer. The authors of the review also concluded that the prospect of reducing the incidence and burden of some of the most prevalent cancers with safe, affordable and tolerable medication that already reduces the risk of the leading cause of death and cardiovascular disease warrants further exploration in clinical trials and observational studies of prognosis and survival. They reported only one ongoing clinical trial of statin use in prostate cancer, registered in clinicaltrials.gov. That trial looked at the effect of preoperative simvastatin vs placebo on the mevalonate pathway synthesis and target activation in benign and malignant prostate cancer among men undergoing prostatectomy as their primary treatment for prostate cancer . We are therefore unlikely to get an answer to this conundrum for some time.
Statins have been reported to reduce PSA levels. This may be particularly important with regard to diagnosis as it may delay the decision for prostate biopsy and prostate cancer diagnosis , but it may also bias the detection of recurrence when comparing statin users vs non-statin users.
The present paper by Chao et al.  concluded that statin use may not prevent prostate cancer progression after radical prostatectomy. Their findings do not provide support for the pursuit of a prospective clinical trial of statin use as secondary prevention among patients with surgically treated prostate cancer. The present paper was a retrospective study involving men with incident prostate cancer, diagnosed between 2004 and 2005, who subsequently underwent radical prostatectomy in Southern California. A total of 1200 men were included, of whom 37% had preoperative and 56% had postoperative statin use. There was a much higher incidence of obesity, diabetes, coronary heart disease and hypertension in the statin-treated group. Of these men, 74.6% received lovastatin, 20% simvastatin, 5% atorvastatin and 0.4% pravastatin. The men were followed up for 5 years after prostatetctomy.
The majority of men in the present study were taking lovastatin. This drug has been shown to inhibit the cell cycle in vivo and this is probably through its cholesterol-lowering effect. High concentrations (50 μm) are required for lovastatin's pleiotropic effects . With regard to cholesterol lowering, there is no evidence that there is a significant inverse association with any of the other cholesterol-lowering agents. This suggests that statin pleiotrophy is important with regard to anti-tumour properties .
Observational studies are always difficult to interpret. In the present study, we do not know when the patients' glycaemic index breached the diabetes threshold or when the patients were diagnosed with diabetes. There is no information on the degree of insulin resistance in these overweight subjects and what drugs were prescribed for diabetes, particularly the use of insulin. Nevertheless, it is interesting that there was an inverse association related to biochemical recurrence for postoperative statin use (hazard ratio = 0.66 (0.41–0.92) P = 0.08). This was measured as the proportion of follow-up time exposed to statins (>67% of follow-up time exposed to statins); however, no dose–response relationship was found. The authors note that follow-up time in the present study was only 5 years and studies with significantly longer follow-up and a greater number of events would be required to shed further insight on the dose–response relationship for the potential protective signals of postoperative statin use as seen in their study.
The authors acknowledge the weaknesses of their study, which include incomplete capture of obesity and smoking, lack of evaluation of the effect of a cumulative dose of statins, a short follow-up time of 5 years, the low number of events, and whether or not biochemical recurrence is always clinically meaningful.
Unfortunately it is highly unlikely that a randomized control trial involving statins in this situation will ever be performed. The majority of men in the 50+ years age group do require a statin for cardiovascular prevention and it is highly likely that any control group would be contaminated by the end of the study.
There is often resistance to taking statin therapy because of excessive media activity about the issue of muscle side effects, but it is widely accepted that the benefit of statin therapy far overcomes the very small risk of myopathy. An editorial published in the Lancet online in May this year showed that statins reduced the risk of serious vascular events by ∼ 21% for a 1 mmol/L reduction in low-density lipoprotein cholesterol in each of five baseline risk groups, including those with the lowest risk of vascular disease. The editorial suggested that we should at least treat everybody with a ≥10% risk over 10 years, but there is benefit from treatment even in patients at lower risk than this .
- 7ClinicalTrials.gov. Statin therapy versus placebo prior to prostatectomy. Available at: http://clinicaltrials.gov/ct2/show/NCT00572468?cond=prostate+cancer&intr=statins&rank=2. Accessed 1 October 2012