Tampere, Finland—The use of statins to lower cholesterol affects prostate-specific antigen, but it has not been clear how that impacts PSA screening performance.
A study published in JAMA Oncology sought to determine whether statin use was associated with outcomes of a randomized PSA-based prostate cancer screening intervention.
In the post hoc subgroup analysis of a cohort of 78,606 men, median age 59 years, in the Finnish Randomized Study of Prostate Cancer Screening, PSA screening was associated with a lower incidence of advanced prostate cancer regardless of statin use but also was associated with a smaller increase in detection of low-grade tumors among statin users. On the other hand, according to Tampere University–led researchers, the association between screening and prostate cancer mortality did not vary by statin use.
"In this study, prostate-specific antigen-based prostate cancer screening was associated with less overdiagnosis of low-risk cancer among statin users, with similar mortality outcomes as in nonusers," the authors write.
A key issue is that PSA screening for prostate cancer is shown to be linked to a small reduction in mortality but, at the same time, a higher rate of overdiagnosis of low-risk tumors.
The study randomized men to PSA screening or routine care from March 1, 1996, to December 31, 1999, with follow-up continuing until December 31, 2015. Included were all men aged 55 to 67 years at baseline and residing in the Tampere or Helsinki districts of Finland. Information on statin purchases from 1996 to 2009 was obtained from a national prescription registry. Data were analyzed from January 1, 2019, to March 31, 2021.
"Although PSA screening was associated with increased prostate cancer incidence among statin nonusers (screening vs control, 11.2 vs 8.6 per 1000 person-years); rate ratio [RR], 1.31; 95% CI, 1.24-1.38), no similar increase in incidence was observed among statin users (6.9 vs 5.9 per 1000 person-years; RR, 1.02; 95% CI, 0.95-1.10; P <.001 for interaction)," the researchers report. "Incidence of low-risk (Gleason score 6) and localized tumors was lower among statin users, whereas detection of tumors with a Gleason score of 8 to 10 was similar. Screening was associated with a lower incidence of metastatic tumors regardless of statin use."
Their findings "suggest that statin use does not materially compromise benefits of PSA-based screening," the authors advise.
"Systematic screening for prostate cancer (PCa) has resulted in overdiagnosis of low-risk tumors and only a modest reduction in PCa mortality," according to the study. "Screening is considered beneficial for early detection of clinically significant PCa and decreasing PCa mortality."
"Currently, the harms of systematic PSA-based PCs screening are considered to exceed the benefits by causing unnecessary diagnoses of clinically insignificant cancers," the researchers add.
Complicating matters is that serum PSA is influenced by benign conditions such as prostatic inflammation, meaning that some commonly used medications, including statins, influence PSA levels. Statins, which inhibit endogenous cholesterol productionÊand block protein prenylation, may lower PSA by reducing intraprostatic inflammation or by inhibiting androgen signaling, according to the study.
"The possible influence of statins on PSA levels could result from improved accuracy of PSA screening in detection of clinically relevant cancer owing to lower PSA levels among statin users, with fewer prostate biopsies for borderline PSA elevations and a reduction in detection of clinically irrelevant cancers," the authors suggest. "On the other hand, lower PSA levels could presumably also lead to delayed detection of PCa, causing cancers to be diagnosed more often at an advanced stage."
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