There was a trend toward a more advanced stage among younger patients (the proportion of patients with advanced tumor stage increasing from 52% to 64%), while the trend among the elderly was opposite (decreasing from 54% to 44%). The proportion of tumors of unknown stage remained constant in both age groups. Between 1975 and 1992 the relative 1- and 3-year survival rates for younger patients with adenocarcinoma have decreased markedly from 59% to 43% and from 36% to 27%, respectively (Table 2); this decrease was most marked for men. After stratification according to stage, relative 1- and 3-year survival rates for adenocarcinoma remained more or less stable (Table 2). For males the 1-year survival rate increased from 35% for birth cohort 1900–1909 to 50% for cohort 1920–1929, but decreased thereafter to 44% for cohort 1940–1949. For women the 1-year survival rate increased from 42% for birth cohort 1910–1919 to 58% for cohort 1940–1949.
Among men with non-small-cell lung cancer in the southeastern part of the Netherlands, the proportion of adenocarcinoma increased since 1975 and for those born since 1920, while among women this proportion remained roughly unchanged. For male patients with adenocarcinoma born since 1930 and for those diagnosed since 1975, the survival rate decreased.
The role of changes in detection or histological tumor typing in the increase in incidence for male patients born after 1920 is likely to be limited; despite better diagnostic techniques and the increase in the number of chest physicians, there was little indication of a shift in the stage of disease at the time of diagnosis. Furthermore, the rise in adenocarcinoma was not caused by an increase in bronchioloalveolar carcinoma, as was found in the United States. 10,11 Others have suggested that the increase in the incidence of adenocarcinoma in the United States was due to the increased use of low-tar filter cigarettes, especially since they only found an increase in adenocarcinoma among smokers. 6,12 The use of filters in longstanding smokers generally results in different inhalation behavior, for example, taking larger puffs and retaining smoke longer to compensate for the lower nicotine yield of filter cigarettes. The subsequent increased deposits of smoking particles in the bronchioles could enhance the risk for tumors in the peripheral lung zones, where the majority of pulmonary adenocarcinomas arise. 13 Furthermore, low-tar filter cigarettes may increase the risk for adenocarcinoma because of their higher nitrate content. 14 The percentage smoking low-tar filter cigarettes in the Netherlands has started to increase later than in the United States, but has steadily been increasing to 78% among male cigarette smokers and to 92% among female cigarette smokers in 1997 (derived from periodic surveys that were conducted for the Netherlands Foundation on Public Health and Smoking). Younger people in the Netherlands were more inclined to smoke low-tar filter cigarettes than the elderly. The change in exposure to filter cigarettes has been less marked for women, because smoking became popular among women only since the 1960s. They mainly smoked low-tar filter cigarettes and the proportion of adenocarcinoma remained considerably higher than for men during the whole study period.
While the prognosis for patients with the other histological subtypes of non-small-cell lung cancer remained unchanged, 8 we have searched for explanations for the decline in both the proportion with early disease and the survival rate for male patients with adenocarcinoma. Since peripheral lung tumors may give late signs, we wondered if the decrease in survival could be explained by the termination of the chest x-ray screening program for tuberculosis since the early 1980s. In a study among lung cancer patients diagnosed in Finland, mainly adenocarcinomas were detected during screening for tuberculosis, and screen-detected cancers had a favorable stage distribution and a better survival. 15 Termination of screening could explain the marked decrease in survival in the early study period. Our data, however, did not show the expected dip in incidence just after the termination of screening, and the survival of adenocarcinoma kept decreasing after 1980–1984, although less so. We hypothesize that, in addition to the effects of the termination of screening, the biological behavior of adenocarcinomas may have shifted toward a more rapidly metastasizing tumor. If so, this might be associated with the shift to smoking more low-tar filter cigarettes since the 1960s, especially by younger men. As indicated above, filter use could result in a deeper penetration of carcinogens in the peripheral lung zones. In this respect, cigarette smoke-induced K-ras mutations are of special interest; they are known to be associated especially with adenocarcinoma and are associated with a poor prognosis. 16–19
In the United States no decrease in survival of adenocarcinoma had occurred between 1978 and 1986, 20 but the increase in incidence of adenocarcinoma in the United States had mainly been caused by an increase in bronchioloalveolar carcinoma (with a fairly good prognosis), 10,11 which was not the case in the Netherlands. In short, the increased use of low-tar filter cigarettes may have been responsible for both the increased incidence and the decreased survival for adenocarcinoma of the lung.
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