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Smoking linked to poor neoadjuvant chemotherapy response, recurrence in bladder cancer
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Cigarette smoking appeared significantly associated with poor pathological response to cisplatin-based neoadjuvant chemotherapy among patients with muscle-invasive bladder cancer who underwent radical cystectomy, according to results of a single-center study.
Additionally, current smokers had a significantly higher risk for disease recurrence.
“Tobacco smoke inhalation appears to be the most common risk factor for bladder cancer, causing more than 50% of bladder cancer cases,” Luca Boeri, MD, urology resident in the division of experimental oncology at IRCCS Ospedale San Raffaele in Italy, and colleagues wrote. “The intensity and duration of smoking have been shown to affect the grade and stage of the bladder cancer, and to be linearly related to the increased risk of disease development.
Boeri and colleagues hypothesized that current smoker status would be linked to higher risk for chemoresistance and impaired response to neoadjuvant chemotherapy among patients with invasive bladder cancer treated with radical cystectomy.
They also sought to test the association between smoking status and disease recurrence or survival.
The researchers consulted a prospectively sustained, institutional radical cystectomy registry to identify 201 patients (median age, 64 years; interquartile range [IQR], 58-72) who underwent the procedure at Mayo Clinic between 1999 and 2015.
They categorized patients’ smoking status as never (n = 58), former (n = 87), and current (n = 56), and classified pathological response to neoadjuvant chemotherapy as complete (ypT0N0), partial (ypTis/Ta/T1,N0) and none (ypT2-4 or ypN+).
Logistic regression analyses assessed the relationship between smoking status and pathological response to neoadjuvant chemotherapy, and Cox regression analyses analyzed risk factors associated with recurrence, overall mortality and cancer-specific mortality.
The researchers found that current smokers had higher rates of significant comorbidities (P = .048) and clinical extravesical disease (P = .017), higher pathological T stage (ypT) and a higher prevalence of preoperative hydronephrosis (P = .02) than patients in the other groups.
Median follow-up was 24.6 months (IQR, 12.3-46.7) for survivors and 22.4 months (IQR, 10.5-48.4) for those who did not experience recurrence.
During the course of the study, 72 patients (35.8%) had disease recurrence and 82 (40.8%) died of secondary causes and 66 (32.8%) died of muscle-invasive bladder cancer.
Current smokers frequently did not respond to neoadjuvant chemotherapy (73.2%; P = .007). Likewise, heavy smokers had a higher rate of no response than never smokers (63.7% vs. 31%; P = .02).
An analysis adjusted for age, sex, Charlson comorbidity index and clinical stage revealed significant associations between former smoker status (OR = 2.28; P = .024) and current smoker status (OR = 4.52; P < .001) and no response to neoadjuvant chemotherapy.
Researchers also found independent associations between current smoking status (HR = 2.14; P = .03) and extravesical pathological tumor stage (HR = 3.31; P < .001) and increased risk for disease recurrence after radical cystectomy. Multivariable analyses confirmed these findings.
Researchers also observed significant associations between overall mortality risk and older age (HR = 1.05; P = .004), extravesical pathological tumor stage (HR = 4.95; P < .001) and lymphovascular invasion (HR = 2.63; P = .001).
large, prospective studies are needed to assess the impact of smoking and smoking cessation on survival outcomes in patients receiving neoadjuvant chemotherapy and radical cystectomy,” the researchers wrote. “As a whole, these results suggest that physicians should have a proactive role in educating patients regarding the detrimental effect of smoking on cancer-specific and overall health outcomes.” – by Jennifer Byrne
Disclosure s : The researchers report no relevant financial disclosures.
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Boeri L, et al. BJU Int. 2019;doi:10.1111/bju.14612.
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