Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study

Abstract

Background: Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level.

Methods: All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments.

Results: A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiagnostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72-0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74-0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55-0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64-0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality.

Conclusion: In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.

Fig 1. Flowchart of patients.

NSSN stands for the National Social Security Number in Belgium.

Fig 2. Subgroup analyses of the association between statin use after diagnosis and overall mortality in patients with ovarian cancer.*

The study population was divided into subgroups according to several categorical covariates. A horizontal line on the figure represents one subgroup and it is divided between postdiagnostic statin users and nonusers (with the size, the number of deaths (+%), and the number of person-years). For each subgroup (ie. line), the survival of postdiagnostic statin users and nonusers were compared and the obtained estimations were graphically represented and reported as HR (CI95%) with corresponding P-values. * CI denotes confidence interval. ^a Adjusted model contains age in categories (≤49 years, 50–74 years, ≥75 years), year of diagnosis (in 3-years bands), stage, cancer treatment within the 9 months (none, surgery only, chemotherapy only, neoadjuvant and adjuvant chemotherapy), comorbidities (diabetes and cardiovascular diseases). ^b Statin use before diagnosis was defined as at least one statin prescription in the year prior to the diagnosis.