Effect of smoking on outcomes of urothelial carcinoma - a systematic review of the literature

CONTEXT: Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC). However, the effect of smoking on outcomes of UC patients remains debated.

OBJECTIVE: To integrate the available evidence regarding the impact of smoking status and smoking exposure on recurrence, progression, cancer-specific mortality, and any-cause mortality in patients with UC of the bladder (UCB) and upper tract UC (UTUC) treated with transurethral resection of the bladder (TURB), radical cystectomy (RC), or radical nephroureterectomy (RNU).

EVIDENCE ACQUISITION: A systematic search of the literature was conducted using the Medline, Embase, and Scopus databases, which was limited to articles published in English between January 1974 and March 2013. Articles were also extracted from the reference lists of identified studies and reviews. We selected 29 articles (15 TURB, 7 RC, and 7 RNU) according to predefined inclusion criteria and the Preferred Reporting Items for Systematic Reviews and Meta-analyses.

EVIDENCE SYNTHESIS: The majority of studies demonstrated an association with disease recurrence in patients treated with TURB, while evidence for associations with disease progression, cancer-specific mortality, and any-cause mortality was less abundant. While two studies showed no association of smoking with outcomes of T1 UCB, there was mixed evidence for an association of smoking with response to intravesical therapy. For patients treated with RC, there was minimal support for an association of smoking with all outcomes. In a majority of studies of patients receiving RNU for UTUC, smoking was associated with intravesical recurrence, disease recurrence, cancer-specific mortality, and any-cause mortality. There was also evidence for a beneficial effect of smoking cessation on UC prognosis. Finally, findings regarding gender-specific effects of smoking on prognosis were contradictory. We note that there was marked heterogeneity in patient populations and smoking categorizations across studies, precluding a meta-analysis.

CONCLUSIONS: Smoking may lead to less favorable outcomes for UCB and UTUC patients, and smoking cessation may mitigate this effect. The current evidence base lacks studies on the effects of smoking on prognosis in numerous clinical demographic subgroups of UC patients, as well as prospective investigation of smoking cessation.