Number of lymph nodes associated with maximal reduction of long-term mortality risk in pathologic node-negative non-small cell lung cancer.

Abstract

Forty-four percent of patients with pathologic node negative (pN0) non-small cell lung cancer (NSCLC) die within 5 years of curative-intent surgical procedures. Heterogeneity in pathologic nodal examination practice raises concerns about the accuracy of nodal staging in these patients. We hypothesized a reciprocal relationship between the number of lymph nodes examined and the probability of missed lymph node metastasis and sought to identify the number of lymph nodes associated with the lowest mortality risk in pN0 NSCLC. We analyzed resections for first primary pN0 NSCLC in the United States Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2009, with survival updated to December 31, 2009. In 24,650 eligible patients, there was a significant sequential reduction in mortality risk with examination of more lymph nodes. The lowest mortality risk occurred in those with 18 to 21 lymph nodes examined. The hazard ratio for all-cause mortality was 0.65 and the 95% confidence interval (CI) was 0.57 to 0.73; for lung cancer-specific mortality, hazard ratio was 0.62 and CI was 0.53 to 0.73 (p<0.001 for both). The median number of lymph nodes examined was only 6. Lymph node evaluation falls far short of optimal in patients with resected pN0 NSCLC, raising the odds of underestimation of long-term mortality risk and failure to identify candidates for postoperative adjuvant therapy. This represents a major quality gap for which corrective intervention is warranted.