Active Smokers Far More Likely to Fail on Chemo for Bladder Ca

Patients with muscle-invasive bladder cancer undergoing radical cystectomy had worse rates of pathological response to neoadjuvant chemotherapy (NAC) if they were current smokers, a single-center study found.

Among 201 patients examined, former smokers were twice as likely (OR 2.28, P=0.024) and current smokers four times more likely (OR 4.52, P<0.001) to show no response to cisplatin-based chemotherapy compared with never smokers, according to Robert Jeffrey Karnes, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.

And both current smoking status (HR 2.14, P=0.03) and tumor stage (HR 3.31, P<0.001) were independently associated with an increased risk of recurrence after radical cystectomy, they reported in BJU International.

“Our present study showed, for the first time, that smoking status was associated with adverse pathological response to NAC in patients with muscle-invasive bladder cancer,” the researchers wrote.

The single-center study included 58 never smokers (28.9%), 87 former smokers (43.3%), and 56 current smokers (27.9%) with muscle-invasive bladder cancer who were treated with cisplatin-based chemotherapy prior to radical cystectomy at the Mayo Clinic.

Current smokers had the highest rate of no response to NAC (73.2%), followed by former (56.3%) and never smokers (39.7%); and rates of complete response were worse in active smokers (17.9%) compared with former (26.4%) or never smokers (43.1%, P=0.007).

While the researchers concluded that large, prospective studies are needed to further assess the impact of smoking and smoking cessation on outcomes in patients with bladder cancer receiving NAC and radical cystectomy, they added that the findings have immediate clinical implications.

“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,” they wrote.

The researchers noted that smoking is responsible for more than half of bladder cancer cases, and that smoking duration and intensity have been shown to impact the grade and stage of disease.

Previous studies have shown a link between smoking and disease progression and recurrence in non-muscle-invasive bladder cancer, but little was known about the impact of smoking on muscle-invasive disease, they wrote.

Several studies have also suggested that smoking may be associated with increased resistance to cisplatin-based chemotherapy.

“In the last decade, the rates of utilization of NAC in patients with muscle-invasive bladder cancer have gradually increased following reports demonstrating survival benefit as compared to radical cystectomy alone,” Karnes and colleagues wrote. “Moreover, several of these trials have shown that pathological response to NAC at the time of radical cystectomy was associated with improved survival. Therefore, the identification of modifiable clinical factors that may affect NAC response is of primary importance.”

With this aim, the researchers examined the impact of smoking status on response to NAC and survival outcomes in this patient population. They reviewed the cases of 201 patients treated with NAC and radical cystectomy for cT2-cT4N0M0 bladder cancer from 1999 to 2015.

Pathological response to NAC was defined as complete, partial, or no response, and clinical and pathological characteristics were analyzed according to smoking status (current, former, never). Logistic regression analyses were used to test the association between smoking status and pathological response to NAC. Cox regression analyses tested risk factors associated with recurrence and overall, and cancer-specific mortality.

ORs for the main findings were adjusted for age, gender, Charlson Comorbidity Index, and clinical stage. The researchers also found that for each unit increase in pack-year history, the risk of having no response to NAC was significantly increased.

“Overall, these findings suggest that both smoking status and smoking quantity may be considered as potential predictors of cisplatin-based NAC response in the clinical setting,” Karnes and colleagues concluded.