Can daily intake of aspirin and/or statins influence the behavior of non-muscle-invasive bladder cancer? A retrospective study on a cohort of patients undergoing transurethral bladder resection
The purpose of this retrospective study was to compare the behavior of non-muscle-invasive bladder cancer (NMIBC) between patients who had undergone transurethral bladder resection (TURB) in chronic treatment with aspirin, statins, or a combination of these two drugs and similarly operated patients who were not treated with aspirin or statins. Using our cohort of patients and the results of other studies on epithelial neoplasms, we aimed to determine whether daily treatment with these medications, widely used for the prevention of cardiovascular disease, can affect the prognosis of Urothelial Bladder Cancer (UBC).The main target in determining the chemopreventive effect of aspirin and other non-steroidal anti-Inflammatory drugs (NSAIDs) is the inhibition of cyclooxygenase (COX) or prostaglandin-endoperoxide synthase, especially its isoform 2, which is overexpressed in many tumor cell lines, including bladder cancer (BC). Many studies have shown that COX inhibitors have a preventive effect and are able to induce remission of BC in animal models.
An additional aim of our study was to analyze the behavior of NMIBC in patients treated daily with statins undergoing TURB. The primary effect of statins is the reduction of low-density lipoproteins, an effect that is associated with an anti-inflammatory action. The possible role of statins in the processes of carcinogenesis and, particularly, in UBC is still not completely defined.
We also focused our attention on patients treated with both aspirin and statins. The effect of this therapeutic combination on the progression and behavior of NMIBC after TURB has not been studied previously. We compared results obtained in this population with results in the other treatment sub-populations and in untreated patients.
Methods and results
This retrospective study was conducted on 564 patients diagnosed with NMIBC who underwent TURB between March 2008 and April 2013. The study population was divided into two main groups: treated (aspirin and/or statins) and untreated. The treated group was further divided into three therapeutic subgroups: Group A (100 mg of aspirin, daily for at least two years); Group B (20 mg or more of statins, daily for at least two years); and Group C (100 mg of aspirin and 20 mg of statins together).
More resections (2,073) and a higher rate of recurrence (54%), number of recurrences (1,073), and number of lesions in recurrence (mean, 2.44) were observed in the treated group than in the untreated group (p < 0.05). In the treatment subgroups, significantly fewer resections, recurrences, and number of lesions in recurrence, as well as a lower percentage of patients with recurrences, were found in Group A than in Groups B and C (p < 0.05).
In our study, long-term aspirin treatment reduced the risk of bladder tumor recurrence, average number of resections, and number of lesions in recurrence in patients who underwent TURB for NMIBC. In contrast, the use of statins increased recurrence rates and progression of the disease and appeared to reduce the protective effect of aspirin in patients treated with both drugs.To the best of our knowledge, this is the first study that investigated the effects of combined aspirin and statin use on the behavior and progression of NMIBC. The results of this group (combined therapies) have demonstrated a statistically increased number of resections (2,143), rate of relapsing patients (57,1%), number of recurrences (1,143), and number of lesions in relapse (2,57) compared with those outcomes in the untreated group and, especially, in aspirin Group (A). Our results suggest that aspirin therapy has a protective role in BC but that statin therapy alone and statin therapy coupled with aspirin therapy do not. Based on this retrospective review, we intend to conduct a prospective, randomized controlled study to conclusively determine the effects of these two categories of drugs on the recurrence rate and the progression of BC.
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