Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative

Abstract

Background: Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.

Study design: We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.

Results: Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.

Conclusions: The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.

Figure 1

Disease-specific survival curves for the entire study population based on the number of lymph nodes examined (continuous line: 16 or more lymph nodes, n = 485, 10-year DSS 55%; dashed line: 7–15 lymph nodes, n = 257, 10-year DSS 47%; P = 0.53).

Figure 2

Subset analysis of disease-specific survival curves after resection of gastric adenocarcinoma stratified by AJCC stage (7^th edition). Although P values for all stages were > 0.05, patients who had 16 or more lymph nodes examined (continuous line) tended to have improved survival compared with patients who had 7–15 lymph nodes examined (dashed line) in Stages I-A through III-A, but not in stages III-B and III-C.

Figure 3

When stages I-A through III-A were combined together, patients with gastric adenocarcinoma who had 16 or more lymph nodes removed (continuous line, n = 269) had improved outcome after resection compared with patients who had 7–15 lymph nodes examined (dashed line, n = 229) with 10-year disease-specific survival rates of 74% versus 57% respectively (P = 0.018). This difference was not observed when stages III-B and III-C were analyzed together (P = 0.55).

Figure 4

When stages N₀ through N₂ were combined together, patients with gastric adenocarcinoma who had 16 or more lymph nodes examined (continuous line, n = 315) had improved outcome after resection compared with patients who had 7–15 lymph nodes examined (dashed line, n = 213) with 10-year disease-specific survival rates of 72% versus 55% respectively (P = 0.023). This difference was not observed in patients with N₃ disease (P = 0.882).

Figure 5

A Cox proportional hazards model was utilized to compute the Hazard Ratio (HR) for gastric cancer related death (black line, red lines illustrate 95% confidence interval) as a function of the total number of lymph nodes removed (Reference is 0 nodes removed). HR was adjusted for T stage, grade, margin status, receipt neoadjuvant chemotherapy, adjuvant chemotherapy or radiation, and institution. On the left, when less advanced stage patients were analyzed (Ŝ_0, more likely to be true N_0-2, n = 676), the HR appears to decrease as the number of removed lymph nodes increases, but there does not appear to be an incremental benefit beyond 16 lymph nodes removed. On the right, when more advanced stage patients were analyzed (Ŝ_1, more likely to be true N₃, n = 163), no significant correlation between the HR and the number of lymph nodes removed was demonstrated.