Effect of formalin fixation on tumor size determination in stage I non-small cell lung cancer

Tumor size is an important prognostic factor in non-small cell lung cancer (NSCLC), but the American Joint Committee on Cancer staging system does not mandate a specific measurement method. Moreover, measuring fresh specimens and formalin-fixed specimens may yield disparate results. Our goal was to evaluate this disparity for stage I NSCLC.

We enrolled 401 patients with stage I NSCLC who underwent surgical interventions and follow-up in our hospital between 1993 and 2002. Tumors invading visceral pleura, involving the main bronchus, or associated with atelectasis or obstructive pneumonitis were excluded. Tumor size was measured immediately after resection by surgeons and after formalin fixation by pathologists. Patients were assigned to one of three groups. Group 1 included 201 patients with tumors of 3 cm or less as indicated by both operation notes and pathology reports. Group 2 included 160 patients with tumors larger than 3 cm by both records. Group 3 included 40 patients with tumors larger than 3 cm according to operation notes but 3 cm or less according to pathology reports. Survival rates were compared.

Mean follow-up was 58 months. Five-year survival was 70.1% in group 1, 49.1% in group 2, and 51.1% in group 3. As expected, there was a significant survival difference between groups 1 and 2 (p < 0.001); however, there was also a difference between groups 1 and 3 (p = 0.006).

Formalin fixation may cause tumor shrinkage and migration from T2 to T1. For accurate tumor staging, size measurements should be performed immediately after resection instead of after formalin fixation. TNM staging should specify how to measure tumor size and the specimen status to be measured.