Does Smoking Cessation Reduce Bladder Cancer Recurrence?

Smoking status has been associated with both an increased risk of developing bladder cancer and worse prognosis, but its impact on the risk of nonmuscle-invasive bladder cancer (NMIBC) recurrence remains controversial.^1–3 Prior studies have used patient self-reporting of smoking status, which may not be as reliable as laboratory-based biochemical measures of smoking status,⁴ leading to an unclear relationship of smoking with bladder cancer recurrence. In this issue of The Journal, Furberg and colleagues (page 1200) evaluated the association between the risk of NMIBC recurrence and current smoking status.⁵ Among a robust prospective sample of 354 ever smokers with recently diagnosed NMIBC, the authors used urinary or salivary measures of cotinine as an objective, biochemically verified measure of smoking exposure.

This study did not find an association with continued smoking and risk of bladder cancer recurrence.⁵ Recurrence risk was, unsurprisingly, significantly associated with receipt of bacillus Calmette-Guérin treatment and prior recurrence rate. Although urinary cotinine provides a more objective assessment of smoking status, limitations of this approach include the transient bioavailability of cotinine (not detectable after 7 days of smoking cessation) and potentially categorizing patients with secondhand smoke exposure and light or intermittent smoking as unexposed to smoke, all which may impact disease recurrence. Cotinine testing does detect nicotine replacement therapy as well as ENDS (electronic nicotine delivery systems), including e-cigarettes, and patients using these would have been classified as current smokers in this study.

As the authors acknowledge, very few patients endorsed using these products, and it seems unlikely that their classification would impact the overall conclusions even though the safety profile of these products is not well known.⁵ Additionally, the predominance of high-grade NMIBC in this study likely represents bladders that have already accumulated tumorigenic mutations due to previous carcinogen exposure and, therefore, smoking cessation does not reduce recurrence risk. While the authors did not identify an association between grade and recurrence risk, stratification of low-risk tumors per the American Urological Association NMIBC risk stratification categories may enrich for tumors with fewer accumulated mutations and demonstrate a different response to smoking cessation. Furthermore, this study did not evaluate the impact of smoking cessation on the progression of bladder cancer, which could also be impacted by persistent exposure to carcinogens through smoking. Despite these acknowledged critiques, the authors appropriately conclude that within this cohort of patients with generally higher-risk NMIBC post-diagnosis smoking exposure was not associated with recurrence, at least in the intermediate term.

An equally important finding is the fact that 22% of ever smokers in this cohort study continued to smoke following a bladder cancer diagnosis.⁵ The authors effectively highlight this finding in the context of the imperative need for continued smoking cessation counseling at all points of urological bladder cancer care regardless of the lack of evidence to suggest an impact on NMIBC recurrence. There remain gaps to advance tobacco use treatment in the urological setting,^6–8 and several opportunities for improvement exist, including partnerships with implementation scientists to break through barriers and provide patient-centered interventions to effectively encourage patients to quit.⁹ Incorporating tobacco use screening and smoking cessation counseling into bladder cancer guidelines may also set the framework to enhance tobacco treatment in bladder cancer survivors.¹⁰