Smoking After Diagnosis Leads to Worse Renal Cell Carcinoma-specific Survival

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Cigarettes may favor VHL-intact RCC, but it is unclear whether cigarette smoking selects for more aggressive histology of RCC in a similar way to, for example, the TP53 mutation in lung cancer.
Cigarettes may favor VHL-intact RCC, but it is unclear whether cigarette smoking selects for more aggressive histology of RCC in a similar way to, for example, the TP53 mutation in lung cancer.

Previous studies linked active cigarette smoking with worse outcomes in genitourinary malignancies such as urothelial carcinoma and prostate cancer, but its effect on outcomes in renal cell carcinoma (RCC) are not well-studied.1,2

Smoking is among the known risk factors for RCC.3 One of the early studies establishing this relationship was the Nurses' Health Study and the Health Professionals Follow-Up Study, which was published in 2005.4 This prospective study included more than 100,000 women and almost 50,000 men and showed that increasing pack-years of smoking was independently associated with the risk for RCC in men and women.

In 2010, data from the Surveillance, Epidemiology, and End Results (SEER) Program database again established a strong correlation between cigarette smoking and kidney cancer.5 More recently, a meta-analysis of more than 24 studies of RCC showed that tobacco smoking significantly increased the risk for RCC and that the risk was greatest among current smokers.6

“Unlike bladder or lung cancers, the causal relationship between smoking and RCC is not as strong,” Dominick Bossé, MD, a clinical research fellow at the Dana-Farber Cancer Institute in Boston Massachusetts, told Cancer Therapy Advisor.

Smoking at Diagnosis

In addition to being a risk factor for RCC development, recent research showed that active cigarette smoking is independently associated with worse overall and cancer-specific survival in patients diagnosed with advanced RCC.7 A multi-institutional Japanese study of 963 patients with stage III or later RCC that showed that smoking 20 or more cigarettes daily at diagnosis was associated with poorer overall and cancer-specific survival.

A 2014 study of 278 patients with metastatic RCC treated with sunitinib again found that active smoking negatively affected progression-free and overall survival.7 A similar study of patients with RCC treated with targeted therapy found that while there was no effect on progression-free survival, active smoking significantly shortened overall survival compared with non-smokers.8

According to Dr Bossé, treatment options for RCC may be limited or affected by a patient's smoking status.

“Patients with severe lung cardiovascular or respiratory comorbidities due to cigarette smoking may not be fit for cytoreductive nephrectomy, which is proven to increase survival in metastatic RCC,” Dr Bossé said. “The selection of systemic therapy for RCC is not driven mainly by the smoking status of patients, however, in those with recent or multiple cardiovascular events, such as myocardial infarction or thromboembolic events. VEGF–tyrosine kinase inhibitors and monoclonal antibodies must be used with caution and may require closer monitoring.”

Smokers are also at greater risk of hypertension, a common adverse effect of the VEGF-targeting therapies.

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