Challenging the Dogma: Stage migration or negative lymph nodes, which of them is the main player on gastric cancer prognosis?

Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. M&M: 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16-25 (n = 258), ≥26 (n = 339). RESULTS: After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). CONCLUSIONS: The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care.

The impact of negative lymph nodes in the survival outcomes of pN+ patients following radical gastrectomy: the inverse lymph node ratio as a better score to study negative lymph nodes.

The impact of negative lymph nodes (LNs) on survival of pN+ patients has been recognized. The weight of negative LNs in an inverse lymph node ratio (nR) should be related to its prognostic impact. Five hundred and two consecutive gastric cancer patients, who underwent radical gastrectomy, were included. Patients were split into groups according to the number of harvested nodes and a cross-tabulation with pTNM stages was performed to test differences in the tumor burden. pN+ patients (n = 296) were split into groups of negative LNs harvested. We tested an alternative formula for computing a lymph node ratio: nR = total number of harvested nodes/total number of positive nodes. The median number of negative LNs was significantly different (p < 0.01) between dissection groups, but not the median of positive nodes (p > 0.05). No difference in pTNM percentage distribution was found between these groups (p > 0.05). When tested, the overall survival improved significantly for groups with larger numbers of negative LNs (p < 0.001). A cutoff of nR ≥ 6 was an independent prognostic factor for survival (p = 0.001), and the survival of pN+ patients with nR ≥ 6 was not different from pN0 patients. The impact of the number of negative LNs on the survival of the pN+ patients was demonstrated. The higher numbers in the numerator of the nR was due to the disproportion between harvested negative LNs and metastatic LNs. Larger ratios imply more negative lymph nodes in relation to positive lymph nodes, which was significantly associated with survival. We believe that the proposed nR is a friendlier to use format because of its intuitive interpretation.