Carcinoma NOS is a Common Histologic Diagnosis and is Increasing in Proportion Among Non-small Cell Lung Cancer Histologies

Background: Recent clinical trials have demonstrated differential survival benefit from chemotherapy regimens according to non-small cell lung cancer (NSCLC) histology. We investigated whether the distribution of carcinoma NOS (not otherwise specified) among NSCLC cases in California have changed over time and determined the prognostic significance of carcinoma NOS.

Methods: Retrospective population-based study of 175,298 NSCLC patients diagnosed histologically or cytologically from the statewide California Cancer Registry from 1989 to 2006.

Results: Carcinoma NOS accounted for 22.1% of all NSCLC patients, was the most commonly diagnosed cytologically (37.0%), and had the poorest 5-year survival estimates (5.8%) and median overall survival (OS, 5 months) among all NSCLC histologies. The proportion of carcinoma NOS had increased significantly from 1989 to 2006 in both males and females, in both histologically and cytologically diagnosed NSCLC, among all four major ethnicities (whites, African American, Hispanic, and Asian), among all age categories, and among all American Joint Committee on Cancer stages. The very elderly (80+ years) had the highest proportion of carcinoma NOS and cytologically diagnosed NSCLC regardless of period of diagnosis. Cytologically diagnosed NSCLC had significantly decreased OS than histologically diagnosed NSCLC (p < 0.0001). Cox proportional hazards regression analysis applied to stage 4 NSCLC patients indicated carcinoma NOS (vs. adenocarcinoma; hazard ratio 1.061, 95% confidence interval 1.039-1.083, p < 0.0001) and cytologically diagnosed NSCLC (versus histologically diagnosed NSCLC, hazard ratio 1.043, 95% confidence interval 1.024-1.062, p < 0.0001) were independent unfavorable prognostic factors for OS.

Conclusions: Carcinoma NOS was a common histologic diagnosis, had been increasing over time among NSCLC, and carried an independent unfavorable prognosis among stage 4 NSCLC patients.