Significant role for lifetime cigarette smoking in worsening bladder cancer and upper tract urothelial carcinoma prognosis: a meta-analysis

PURPOSE: Although cigarette smoking is a well-established risk factor for urothelial cancer (UC), its role in UC prognosis is still undetermined. This meta-analysis aimed to quantify the role of lifetime smoking history on bladder cancer recurrence, progression and survival, by pooling available data on non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC) and upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A total of 24 studies, comprising data from 13,114 BC and 2,259 UTUC patients, were included in this meta-analysis. Publication bias was addressed through Eggers test and the heterogeneity between studies was assessed by the I2 test statistic and subgroup analyses. RESULTS: Current smokers at diagnosis are at an increased risk of developing local recurrences in NMIBC (HR=1.27, 95% C.I. = 1.09-1.46) and smoking MIBC patients are at an increased risk of dying due to BC (HR=1.23, 95% C.I. = 1.02-1.44). In the UTUC population smokers have both an increased risk of recurrence in the operative bed (HR=1.57, 95%C.I. = 1.19-1.95) and of dying due to UTUC (HR=1.53, 95%C.I. = 1.13-1.92). We did not identify significant heterogeneity between included studies. CONCLUSIONS: The body of evidence is limited due to the absence of prospective studies. However, the results from this meta-analysis unambiguously support the hypothesis that lifetime cigarette smokers are at an increased risk of developing a more malignant type of urothelial carcinoma associated with worse prognosis.