Statins Are Not Associated with Improved Bladder Cancer Outcomes in Patients with Early-Stage Bladder Cancer Treated with BCG Immunotherapy

TL;DR

This study found that taking statins alongside BCG treatment for bladder cancer does not improve cancer outcomes, despite a link to better overall survival.

Contribution

The study provides real-world evidence that statins do not enhance BCG immunotherapy outcomes for non-muscle invasive bladder cancer.

Findings

Statin use was not associated with reduced cancer recurrence or progression in BCG-treated bladder cancer patients.

Statin use was linked to improved overall survival but not cancer-specific survival in these patients.

The study confirms statins' cardiovascular benefits but not their benefit for bladder cancer outcomes.

Abstract

While BCG immunotherapy remains the gold standard of care for non-muscle invasive bladder cancer (NMIBC) with an intermediate or high risk of progression, many problems have come to light with its increasing clinical application, including its attainability, intolerance, and relapse odds. There are conflicting reports on the use of statins in addition to standard cancer treatment to improve outcomes for patients due to its inhibition of DNA replication, cell proliferation, and TH1 cell inhibition with various cancers in vitro. This study aims to examine the presence of any sort of relationship between BCG treatment, statins, and their potential concomitant effect on non-muscle invasive bladder cancer. If statins prove to be the miracle addition that some studies have claimed them to be, it could mean a breakthrough in cancer treatment options.

Background: Statins are commonly used cholesterol-lowering drugs with evidence of additional chemoprotective and immunomodulatory effects resulting from the inhibition of DNA replication, cell proliferation, and TH1-cell inhibition. There are conflicting reports regarding the potential benefit of concurrent statin treatment on non-muscle invasive bladder cancer (NMIBC) and specifically on intravesical Bacillus Calmette–Guerin (BCG) outcomes. We therefore aimed to analyze the effects of concurrent BCG and statin use in patients with NMIBC. Methods: National Veterans Affairs databases were used to retrospectively identify men with NMIBC between 2000 and 2010 who were treated with BCG. Pharmacy data was interrogated, and patients were divided according to statin therapy status. Statins had to be given at the beginning of BCG treatments and continued for at least 6 months. Cox proportional hazard ratios after inverse propensity score-weighted and competing risks adjustments were calculated for recurrence, secondary events (e.g., progression), cancer-specific survival, and overall survival. Results: Among 8814 patients, with a median follow-up of 11.3 years, statins were used by 38% of the patients. Patients taking statins were older (71 vs. 68, p < 0.0001), had more comorbidities (Charlson Comorbidity Index (CCI > 2; 38.6% vs. 31.4%, p < 0.0001), and had a higher-grade disease (40.2% vs. 34.3%, p < 0.0001) compared to those not on statins. After adjusting for stage, grade, age, race, CCI, agent orange exposure, and year of diagnosis, Cox proportional hazard analysis revealed no association with recurrence (HR 1.05, 95% CI 0.97–1.15, p = 0.23), secondary events (HR 0.91, 95% CI 0.80–1.05, p = 0.189), or bladder cancer specific survival (HR 0.88, 95% CI 0.76–1.02, p = 0.09) of statin use. However, statins were associated with improved overall survival (HR 0.89, 95% CI 0.83–0.96, p = 0.002). Conclusions: Concurrent statin and BCG use in patients with NMIBC was associated with improved overall survival, but not recurrence, secondary events, or bladder cancer-specific survival. These results confirm the real-world well-established cardiovascular benefit of statin treatment and primary preventive care. However, this large population study did not find any association between statins and the outcomes of patients with NMIBC treated with BCG immunotherapy.

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