Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis

Abstract

Objective: To systematically review the evidence that smoking cessation after diagnosis of a primary lung tumour affects prognosis.

Design: Systematic review with meta-analysis.

Data sources: CINAHL (from 1981), Embase (from 1980), Medline (from 1966), Web of Science (from 1966), CENTRAL (from 1977) to December 2008, and reference lists of included studies.

Study selection: Randomised controlled trials or observational longitudinal studies that measured the effect of quitting smoking after diagnosis of lung cancer on prognostic outcomes, regardless of stage at presentation or tumour histology, were included.

Data extraction: Two researchers independently identified studies for inclusion and extracted data. Estimates were combined by using a random effects model, and the I(2) statistic was used to examine heterogeneity. Life tables were used to model five year survival for early stage non-small cell lung cancer and limited stage small cell lung cancer, using death rates for continuing smokers and quitters obtained from this review.

Results: In 9/10 included studies, most patients studied were diagnosed as having an early stage lung tumour. Continued smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% confidence interval 1.15 to 7.54) and recurrence (1.86, 1.01 to 3.41) in early stage non-small cell lung cancer and of all cause mortality (1.86, 1.33 to 2.59), development of a second primary tumour (4.31, 1.09 to 16.98), and recurrence (1.26, 1.06 to 1.50) in limited stage small cell lung cancer. No study contained data on the effect of quitting smoking on cancer specific mortality or on development of a second primary tumour in non-small cell lung cancer. Life table modelling on the basis of these data estimated 33% five year survival in 65 year old patients with early stage non-small cell lung cancer who continued to smoke compared with 70% in those who quit smoking. In limited stage small cell lung cancer, an estimated 29% of continuing smokers would survive for five years compared with 63% of quitters on the basis of the data from this review.

Conclusions: This review provides preliminary evidence that smoking cessation after diagnosis of early stage lung cancer improves prognostic outcomes. From life table modelling, the estimated number of deaths prevented is larger than would be expected from reduction of cardiorespiratory deaths after smoking cessation, so most of the mortality gain is likely to be due to reduced cancer progression. These findings indicate that offering smoking cessation treatment to patients presenting with early stage lung cancer may be beneficial.

Conflict of interest statement

Competing interests: PA has done consultancy work for the manufacturers of smoking cessation drugs. AP has been reimbursed by Pfizer for attending a conference.

Figures

Fig 1 Flow of studies through trial

Fig 2 Effect of continued smoking on all cause mortality and recurrence in non-small cell lung cancer. Weights are from random effects analysis. *Adjusted for age, sex, type of operation, histology, postoperative radiotherapy, N status, T status, and previous malignancies. †Adjusted for sex, histology, and cumulative smoking

Fig 3 Effect of continued smoking on all cause mortality, development of a second primary, or recurrence in small cell lung cancer. Weights are from random effects analysis. *Adjusted for sex, age, and volume of limited disease. †Adjusted for sex, age, performance status, etoposide, radiotherapy, and cumulative smoking