Standardizing the classification of gastric cancer patients with limited and adequate number of retrieved lymph nodes: an externally validated approach using real-world data

Abstract

Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N’) resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. Significant difference in OS between the Limited and Adequate set (corresponding N0–N3a) using the 8th AJCC system was observed but the OS of N0_limited vs. N1_adequate, N1_limited vs. N2_adequate, N2_limited vs. N3a_adequate, and N3a_limited vs. N3b_adequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N’ classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N’0 = N0_adequate + pT1N0M0_limited, N’1 = N1_adequate + N0_{limited (excluding pT1N0M0limited)}, N’2 = N2_adequate + N1_limited, N’3a = N3a_adequate + N2_limited, and N’3b = N3b_adequate + N3a_limited). This N’ classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN’M system over the 8th AJCC edition and was successfully validated using the SEER dataset. The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs.