Statins are Associated with Reduced Overall and Cancer-Specific Mortality in Patients Undergoing Radical Cystectomy for Bladder Cancer

Abstract

BACKGROUND: Existing literature provides contrasting data on statin use and bladder cancer (BC) outcome. OBJECTIVE: We evaluated whether (chronic) statin use was associated with clinical outcomes in patients with BC undergoing radical cystectomy (RC). METHODS: Using provincial health administrative databases, we retrospectively identified BC patients undergoing RC in Quebec province in 2000-2015, and collected data from two years before RC until December 2016 or death. We compared patients who chronically used statins before RC to never statin users. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. Covariates in multivariable analyses were age, sex, Charlson's comorbidity index, year of RC, distance to hospital, hospital type, hospital's and surgeon's annual RC volume, and neoadjuvant chemotherapy. RESULTS: Our cohort contained 1406 chronic and 1754 never statin users. Five-year overall, BC-specific and recurrencefree survival rates were 40.5% (95% confidence interval (95%CI) 37.8-43.2%), 52.8% (95%CI 49.8-55.7%), and 50.1% (95%CI 47.2-53.0%) for chronic statin users, versus 34.9% (95%CI 32.5-37.2%), 45.5% (95%CI 42.9-48.1%), and 43.4% (95%CI 40.9-45.9%) for never statin users (p ≤ 0.001). In multivariable analyses, hazard ratios (HR) for death, BC-specific deaths and recurrences were 0.83 (95%CI 0.75-0.91), 0.81 (95%CI 0.72-0.91), and 0.83 (95%CI 0.74-0.93) for chronic statin users, respectively. Similar observations were made in patients with diabetes and/or cardiovascular comorbidities (p ≤ 0.001). Clinical outcome was not improved in patients who started statins in the year following surgery compared to never statin users (p > 0.4). CONCLUSIONS: Chronic statin use is associated with improved clinical outcome in BC patients undergoing RC in Quebec.

HMG co-reductase expression and response to intravesical Bacillus Calmette-Guérin in patients with high grade non-muscle invasive urinary bladder cancer receiving statins

“…A similar observation has been reported in muscle invasive urinary bladder cancer by Wissing et al 27 This suggests that the role of statin as a long-term therapy to reduce distant metastasis and bladder cancer mortality needs further research. An increased HMGCR expression seen in our study in non-responders indicates that statins induced inhibition of HMGCR and inhibited the mevalonate pathway within the tumour or by lowering circulating levels of cholesterol negatively increased expression of HMGCR proteins.…”

Chronic prednisone, metformin, and nonsteroidal anti-inflammatory drug use and clinical outcome in a cohort of bladder cancer patients undergoing radical cystectomy in Québec, Canada

“…In Québec province in Canada, we have linked several provincial administrative datasets to create a cohort of patients undergoing radical cystectomy (RC) for bladder cancer between 2000 and 2015 [ 4 ]. Using this cohort, we previously identified an association with chronic statin use and improved survival in bladder cancer patients [ 5 ], but could not confirm earlier reports that 5α-reductase inhibitors and α 1 -blockers may be associated with improved bladder cancer outcome [ 6 ].…”

“…Similar to previous publications [ 5 ], patients were considered to be chronic, preoperative users of medication when the time between first and last prescription in our database was ≥ 365 days, and when the date of first prescription was before the date of RC. For postoperative medication use, we included all patients who had ≥ 1 prescription in the year following surgery.…”

“…Endpoints were recurrence-free, bladder cancer-specific, and overall survival. Detailed definitions of these outcome parameters have been provided previously [ 5 , 6 ]. Date of RC was considered t = 0.…”