Lung Cancer Prognosis
In general, a “never smoker” is a person who has smoked no more than 100 cigarettes in his/her lifetime. Getting reliable data on the occurrence of lung cancer amongst non-smokers is difficult because most cancer registries (population-based), including the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database, generally do not gather information related to the patient’s smoking habits. Data available with SEER has been associated with tobacco use information (population-based), but it can only be used to determine occurrence of lung cancer amongst never smokers within wide geographic areas.
Incidence
Globally, the incidence of lung cancer amongst never smokers comprises around 15% of cases in men and about 53% in women. Major geographic differences exist, especially in Asia, where around 60 to 80 percent of female lung cancer patients are never smokers.
In an analysis carried out in the United States, it was estimated that around 19% of lung cancer cases in females occurs in never smokers, in comparison to around 9% in males. These results have been derived from an analysis of data pertaining to patients in five large cohort studies conducted in the United States. The age-adjusted occurrence rate of lung cancer in case of never smokers (within the 40 to 79 age bracket) varied between 11.2 and 13.7 for every 100,000 person-years for males and between 15.2 and 20.8 for every 100,000 person-years for females. These occurrence rates are similar to the occurrence rates of myeloma in males (13.2 per 100,000) or cervical cancer in females (15.4 per 100,000) in the United States. In comparison, the age-adjusted rates, relevant to the incidence of lung cancer amongst current smokers in the same cohorts were about 12 to 30 times higher.
During an analysis of lung cancer patients who were diagnosed between 1991 and 2005 in Southern California, a unique test-mining programming algorithm was used to assess smoking status based on data and information sourced from electronic medical record abstracts available with the regional cancer registry. It was determined during the study that approximately 8.9 percent of more than 25,000 patients classified under the known smoking status were never smokers. This included 6 percent of male patients and 14 percent of female patients.
However, in another analysis involving 13 cohorts and 22 cancer registries, there was no apparent difference in the occurrence rate of lung cancer amongst never smokers by sex overall, even though the incidence rate amongst never smokers was higher in case of women in comparison to men aged 40 to 59 years. It was demonstrated through this multinational analysis that the age-standardized occurrence rates for lung cancer (per 100,000 as per the 2000 world population age standard) in case of female patients were 15.0 for Asian women, 12.4 for women of European descent, and 19.4 for women of African American descent. This compared to incidence rates of 12.9, 11.2, and 12.3, respectively, for men of Asian, European, and African-American background.
With studies generating conflicting results, it is not clear whether there is a change in the incidence of lung cancer amongst never smokers:
- A study conducted under the Swedish construction worker’s health care program that is associated with their national cancer registry, demonstrated a significant increase in the age-adjusted occurrence rate of non-smoking lung cancer. In this study, incidence rates for the period 1976 to 1980 were compared with those of 1991 to 1995 (1.5 against 5.4 per 100,000).
- In two American Cancer Society prevention study cohorts, a statistically significant, yet smaller increase was recorded in the mortality rate in women resulting from non-smoking related lung cancer. Between 1982 and 2000, data from the period 1959 to 1972 was compared to that of 1982 to 2000 (12.3 against 14.7 per 100,000). There was no change in case of men.
- Indirect evidence is available from a series of approximately 12,000 patients diagnosed with lung cancer in Southern California. Comparisons of data between 1995 to 1999 and 1999 to 2003 revealed that the percentage of never smokers diagnosed with bronchioloalveolar carcinoma rose to 26 percent from 19 percent, whereas in case of other types of lung cancer, it increased to 9.4 percent from 8.6 percent.
- Data available from the United Kingdom does not show any evidence of an increase in the incidence of lung cancer amongst never smokers. In a comparison involving 2 case-control studies carried out at the same hospitals and community environment in 1950 and in 1990, there was no change in the percentage of never smokers among men with lung cancer, even though in case of never smokers among the controls, the percentage increased to 19 percent from 4.5 percent. During this time, the percentage of lung cancer amongst female never smokers dropped dramatically, whereas the rate of smoking amongst the controls recorded a less significant drop.
- In a single institution evaluation carried out in Japan, it was revealed that during the 30-year period between 1974 and 2004, the percentage of never smokers, early stage NSCLC patients increased to 33 percent from 16 percent,
As opposed to this, the large pooled study of 13 cohorts compared new observed rates with those in Connecticut during the 1930s when smoking amongst women was very rare and did not find any significant change in due course.
In order to carefully evaluate trends in the occurrence rate of lung cancer in never smokers, cancer registry data will be required to collect information about the smoking status of patients. It can be a challenge to obtain self-reported smoking status, but the effectiveness of this method has been established in several studies which have recorded only small smoker misclassification rates.
Sex
In spite of the higher occurrence rate of lung cancer amongst never smokers in women in comparison to men in several studies, the age-adjusted mortality rate of lung cancer amongst never smokers was higher in case of men in comparison to women in two American Cancer Society cancer prevention study cohorts. Both these cohorts combined included a significant percentage of patients of European descent in a larger pooled assessment of 13 cohort studies and several different cancer registries which recorded age-standardized lung cancer mortality rates of 12 for every 100,000 in case of men and 9.5 for every 100,000 in case of never smoking women of European descent. Amongst Asians, the rates were 26 and 16.1 per 100,000 respectively for men and women. Even though women with lung cancer have higher life expectancy in comparison to men, it is not known whether this is enough to explain the differences recorded between incidence and mortality.
In comparison, in a Japanese study, it was noticed that 33 percent of lung cancer related deaths in men and 85 percent of lung cancer related deaths in women were not associated with cigarette smoking. The percentage of never smoking women diagnosed with lung cancer is much higher in Japan.
Ethnicity
The risk of developing smoking-related lung
cancer varies by race/ethnicity.
Precise data on the variation in rates of lung cancer (based on race or
ethnicity) amongst never smokers is extremely limited.
- Results derived from a SEER database study carried out in the western United States demonstrated higher rates of lung cancer histologies related to non-smoking lung cancer amongst Filipina and Chinese women in comparison to white women, indicating that these groups have higher percentage of never smoking lung cancer.
- In a Southern California analysis involving more than 20,000 patients demonstrated that in case of women, 46 percent of all lung cancer cases in Asia Pacific was in never smokers in comparison to 25 percent in Hispanics, 10 percent in non-Hispanic Whites and 11 percent in African Americans.
- In a Northern California study of lung cancer cases registered between 1998 and 2008, it was revealed that in case of women, of all identified lung cancer cases, 71 percent of cases amongst Asian/Pacific Islanders involved never smokers. In comparison, it was 35 percent in case of Hispanic women and 40 percent in case of non-Hispanic whites.
- More data on this subject is available from a large pooled examination of cohort and registry data which shows wide differences in incidence and mortality rates of non-smoking related lung cancer, even within specific Asian countries, including Thailand and China, but largely increased rates in African Americans in comparison to other ethnic groups.
More research is required to gain a better understanding of the racial/ethnic differences associated with this disease.
Age
While it has been suggested that lung cancer,
in case of never smokers, occurs at a younger age, the same has not been
confirmed in a recent cohort study in Western populations. However, in
studies conducted in Asia, it has been noticed that lung cancer, in case
of never smokers, occurs mostly amongst younger people.