Specific molecular signature redefines the role of posterior and para-aortic (D2 plus) lymphadenectomy in gastric cancer: Rethinking surgical indications

Posterior and para-aortic (D2 plus) lymphadenectomy is still controversial in gastric cancer surgery, as potential oncologic benefit must be balanced against increased technical complexity.Extended lymph node dissection aims to remove residual regional disease, improve staging, and control locoregional recurrence.This review synthesizes the recent literature on D2 plus in advanced gastric cancer, with particular attention to molecular profiling, response to neoadjuvant therapy, and the role of conversion surgery in oligometastatic disease.D2 plus should not be considered routine but may be evaluated in selected patients with bulky nodes in extragastric regions or isolated para-aortic involvement responding to systemic therapy.Pathological response appears to be the strongest prognostic determinant, and persistent nodal burden after neoadjuvant chemotherapy identifies patients with poor survival.Furthermore, molecular subtypes influence biology and expected benefit from therapy: Microsatellite instable tumors may preserve limited propensity for extensive nodal spread, programmed cell death ligand 1 + expression is associated with sensitivity to immunotherapy, microsatellite stability/epithelialmesenchymal transition is associated with aggressive behaviour and peritoneal dissemination and may benefit from prophylactic intraperitoneal chemotherapy, while human epidermal growth factor receptor 2+ tumors maintain a more uncertain behaviour.In selected patients with oligometastatic disease, D2 plus may be integrated into a conversion surgery strategy.D2 plus should be adapted to treatment response and biological profiling.Given that residual nodal burden may outweigh primary tumor response, a better understanding of the molecular features of gastric cancer may help identify patients who are most likely to benefit from posterior and para-aortic lymphadenectomy.