Reversibility of bronchial marked atypia: implication for chemoprevention

Marked atypia (MA) is considered to represent a late stage in the sequence of cellular changes leading to carcinoma. In 1974 we undertook a sputum cytology (SC) survey of uranium workers (UW) and controls (Cancer 1980; 45:1273). Sixteen cases of MA (four with cells suspicious of malignancy) were diagnosed among the initial cohort of 292 male smokers; 11/172 (6.4%) underground UW; 4/78 (5%) surface UW; and 1/42 (2.4%) male controls. Follow up consisted of at least three yearly SC; in addition, selective segmental fiberoptic bronchoscopy was performed yearly for the first 3 years of observation. Three of the four-cases with marked atypia and suspicious malignant cells developed lung cancer. The remaining cases were followed for an average duration of 54 months; all 13 reverted to mild atypia or to normal cytologies. The high frequency of reversibility of MA will cause difficulties in interpreting results of chemoprevention trials if MA is used as the sole marker of effect. Chemoprevention trials should focus on differences in cancer incidence rates between treated and control groups at high risk of developing lung cancer and not on the reversibility of MA as the sole marker of effect.