The definition of “R1” lymph node dissection status in patients undergoing curative-aim gastrectomy for gastric carcinoma: A proof of concept study

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide [1]. For patients in the advanced stage ( ≥ T2 and/or N+), the use of multimodal strategies both in the neoadjuvant and adjuvant setting has been demonstrated to benefit survival [2], even though the cardinal treatment for GC remains radical surgery (gastrectomy with proper lymphadenectomy and negative resection margins - R0 resection). However, many studies have demonstrated that the actual benefit of R0 resection is limited to patients with “confined” local (up to T2-3) and regional (up to N1-2) GC [[3], [4], [5]] and that the role of R0 resection seems more relevant in patients with node-negative disease [6,7]. The survival rate of patients with positive resection margins (R1 resection) is significantly worse than that of patients with R0 resection margins [6]; this is mostly due to a higher rate of systemic recurrence. Accordingly, R1 resection is currently more often considered a marker of underlying aggressive tumor biology rather than a risk factor for local recurrence in most patients with locally advanced GC [8].

Lymph node (LN) involvement is another leading prognostic factor for patients undergoing curative-aim gastrectomy. Since the AJCC/TNM 5th edition, a quantitative (numeric-based) LN staging system has been favored over a qualitative one (anatomic based) due to the simplicity and overall prognostic advantage. However, information on the entity and pattern of LN involvement (i.e., lymph-node ratio, involvement of the central node stations or of the second level LN) could improve the prognostic stratification of GC [[9], [10], [11]].

The dismal prognosis associated with extensive LN disease, especially when extraperigastric LN stations are positive, could be due to unresected metastatic lymph nodes beyond the surgically dissected area. Theoretically the prognosis of patients with a risk of unresected metastatic lymph nodes, even after R0 resection, could be considered similar to the prognosis of patients undergoing R1 resection on the gastrectomy margins. This assumption could have relevant implications for the definition of true radical surgery and from a therapeutic point of view in terms of promoting more extensive lymph node dissections and/or the administration of postoperative loco-regional therapy. Therefore, the aim of this study was to define and investigate the role of “R1 lymph node dissection” from a prognostic point of view.

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