Continuing Debate on D2 Lymphadenectomy for Gastric Cancer

Abstract

Despite the favorable results with extended (D2) lymphnode dissection from specialized institutions [1, 2], thereis no end to the debate about the optimal extent of sur-gery for nonmetastatic gastric cancer [3–5]. D2lymphadenectomy has been the standard procedure inEast Asian countries, particularly in Japan and Korea.Multiple retrospective studies, including analyses of datafrom large databases, that have been recently reviewed [6,7] and a recent randomized, relatively small, phase IIIclinical trial from Taiwan [8] have shown an overallsurvival for all curatively resected patients; subgroupanalysis has also demonstrated a survival benefit in bothstage II and stage III disease [9–11]. However, in Westerncountries, previous randomized clinical trials (RCTs)failed to demonstrate an overall survival benefit, and atpresent there is no level I evidence from RCTs or outsidespecialized Western institutions of the survival benefit ofD2 dissection.The recent report in this journal [12] adds furtheruncertainty about the stage II-specific survival advantageof D2 dissection. The 5-year survival rate of 326 patientswith stage II disease was analyzed. In multivariate anal-ysis, the extent of lymph node dissection was anindependent prognostic factor in the T3N0 group but notin the T2N1 subgroup among the stage II patients. Thisfinding is hard to explain. Because T3N0 patients had nonode-positive disease, how did D2 surgery improve sur-vival? The view of micrometastatic nodal disease tojustify the T3N0-specific survival benefit still remains acontroversial topic. A large-scale RCT with the power forsubgroup analysis can elucidate the question of stage-specific survival benefit of D2 over D1 dissection. How-ever, experienced surgeons are convinced about the safetyand efficacy of D2 resection and it is hard to participatein a RCT in which they have to perform a D1 resectionthat may harm their patients.Treatment of gastric cancer with surgery and adjuvanttherapy has become much more controversial [13]. InJapan, standardized D2 surgery followed by S-1 chemo-therapy has been established as the standard of care forstage II/III disease [14]. In the USA and Europe, neither theextent of surgery (D1 vs. D2) nor the timing of theadministration of chemotherapeutic regimen (before orafter surgery) has been established [15–20].Personalized medicine represents a major research goalfor this century. In particular, clinical use of robust bio-markers to guide preventive and therapeutic interventionwould maximize the benefits for patients with varioussolid tumors [21]. At present, the personalized preventiveand therapeutic approach is a reality only for hereditarydiffuse gastric cancer in carriers of mutations in CDH1gene [22, 23] or hereditary breast-ovarian cancer inwomen with BRCA1 or BRCA2 mutations [24–29]. Nev-ertheless, tailored management of sporadic cancer [30, 31]is much more complicated because of the involvement ofa large number of cancer genes. Complex biologicalprocesses, including cancer heterogeneity, angiogenesis,and microenvironment, should be better understood, andmany challenges and hurdles remain to be overcome toachieve a personalized practice for individuals with can-cer [32, 33]. Currently, a comprehensive systematictreatment-guided algorithm is provided to tailor the mosteffective therapeutic approach for individual patients withgastric cancer [34].