Association of Biochemically Verified Post-Diagnosis Smoking and Nonmuscle-Invasive Bladder Cancer Recurrence Risk

Abstract

Purpose:Our goal was to determine the association between biochemically verified post-diagnosis smoking exposure and nonmuscle-invasive bladder cancer (NMIBC) recurrence risk.Materials and Methods:We conducted a prospective study of 354 NMIBC patients with a smoking history undergoing care between 2015 and 2018. Patients contributed at least 2 biospecimens during followup which were tested for cotinine to determine biochemically verified post-diagnosis smoking exposure (yes/no). Our primary endpoint was time to first recurrence after study start date. We examined whether post-diagnosis smoking exposure was associated with recurrence risk in multivariable Cox proportional hazards models that accounted for demographics, clinicopathological variables, time since diagnosis and pack-years.Results:Patients were predominantly White, male and had a median age of 68 years. Most patients had Ta disease (62%) and tumors of high grade (68%). Intravesical bacillus Calmette-Guérin was given to 63% of the cohort. Patients were followed for a median of 3.6 years since study start. Post-diagnosis smoking exposure was detected in 22% of patients, and 38.7% (137) of patients experienced a recurrence during followup. In multivariable models, only bacillus Calmette-Guérin treatment and prior recurrence rate were significantly associated with recurrence. There was no association between post-diagnosis smoking exposure and recurrence risk (HR: 0.73, 95% CI: 0.45–1.20).Conclusions:In a cohort of patients with predominantly high risk NMIBC, post-diagnosis smoking exposure was not associated with NMIBC recurrence. However, smoking cessation support remains a critical component of cancer care given that the benefits of quitting extend far beyond NMIBC recurrence.

This Month in Adult Urology

“…Furberg at al (page 1200) from New York, New York add more detail to this discussion with a prospective study of 354 patients with bladder cancer and assessing biochemically verified post-diagnosis smoking exposure. 5 In this cohort, most with higher risk nonmuscle-invasive bladder cancer, smoking exposure was detected in 22% of patients. After a median followup of 3.6 years, the authors were unable to detect any association between post-diagnosis smoking exposure and recurrence risk.…”

Does Smoking Cessation Reduce Bladder Cancer Recurrence?

“…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.…”

“…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.…”

“…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.…”

“…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.…”