Quantified smoking status and non-small cell lung cancer stage at presentation: Analysis of a North Indian cohort and a systematic review of literature

Background: There are variable observations in published literature regarding smoking status and stage of lung cancer (LC) with positive, negative and no associations being reported. In particular, data regarding the association of quantified smoking status (QSS) with non-small cell lung cancer (NSCLC) stage at the time of diagnosis is limited. In India, bidi - the hand rolled form of tobacco wrapped in the dried tendu leaf - is the most common smoking product. The current study was conducted to assess stage differences, if any, based upon QSS, among newly diagnosed LC patients. 
Methods: A systematic review of English literature was performed for previous publications that had assessed NSCLC stage differences in relation to QSS. Collected data on demographic and disease characteristics of 654 LC patients presenting to the authors’ institute was also analyzed. Smoking index (SI) was used for QSS and was defined as number of bidis and cigarettes smoked per day multiplied by years smoked. Patients were categorized as never-smokers [Group I, n=151]; light/moderate smokers (SI=1-300) [Group II, n=202] and heavy smokers (SI ≥301) [Group III, n=301]. Multivariate logistic regression analysis (LRA) was performed to derive adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Among the 520 NSCLC patients, mean [standard deviation (SD)] age in groups I, II and III was 54.5 (12.5), 58.6 (9.9) and 61.2 (9.4) years respectively (P<0.001). Percentage of males in the three groups was 48.1%, 88.0%, and 97.9% (P<0.001). Age and gender differences between groups I, II and III were also significant among 134 small cell lung cancer patients with mean (SD) ages of 44.0 (10.6), 55.7 (10.3) and 58.9 (9.3) years (P<0.001) and percentage of males being 50.0%, 90.4% and 95.5% respectively (P<0.001). Among NSCLC patients, distribution in groups I, II and III respectively of squamous (28.1%, 50.0% and 57.9%) and non-squamous histologies (59.3%, 37.3% and 27.2%) differed significantly (P<0.001). Stage distribution observed for NSCLC patients in groups I, II and III respectively was as follows: stages I-IIIA (8.1%, 19.3 and 18.7%), stage IIIB (24.4%, 34.7% and 42.1%) and stage IV (67.4%, 46.0% and 39.1%). The difference was statistically significant (P<0.001). Differences remained significant (P<0.001) for presence of extrathoracic disease [ETD] (41.5%, 28.0% and 16.6%). On multivariate LRA, SI ≥301 was the only variable that was independently associated with both advanced stage (IIIB-IV) [OR=0.25 (95% CI=0.11-0.61)] and ETD [OR=0.29 (95% CI=0.16-0.53)] at presentation.
Conclusions: Among newly diagnosed NSCLC patients in North India, significant differences exist, based upon SI, for disease stage. Heavy smoking was independently associated with lower odds of having advanced stage as well as with lower odds of having ETD at the time of diagnosis. This observation of the current study however requires confirmation by larger prospective studies.