Early observations and pilot data that first suggested a new direction
The Dutch Gastric Cancer Trial, initiated in 1989, was the first large Western RCT to compare D1 (limited) versus D2 (extended) lymphadenectomy for gastric cancer. Among 1,078 randomized patients (711 treated with curative intent), D2 dissection was associated with significantly higher operative mortality (10% vs 4%, p=0.004), complications (43% vs 25%, p<0.0001), and reoperation rates (18% vs 8%, p<0.001). These early results cast doubt on the value of extended lymphadenectomy in Western practice.
Landmark RCTs and pivotal trials that established the evidence base
The critical 15-year follow-up of the Dutch trial (2010) reversed the initial negative impression. Despite the early excess morbidity, D2 lymphadenectomy was associated with lower locoregional recurrence and gastric cancer-related death rates than D1 surgery at 15 years. This finding supported D2 dissection when performed safely, and the initial high mortality was attributed to the learning curve and the inclusion of pancreaticosplenectomy in D2 dissection, which was subsequently abandoned. Japanese and Korean surgical outcomes with D2 dissection consistently demonstrated lower mortality (2-3%), confirming that the procedure was safe in experienced hands.
Follow-up studies, subgroup analyses, and real-world validation
KLASS-02 (2019), a Korean multicenter RCT of 1,050 patients with locally advanced gastric cancer, demonstrated that laparoscopic D2 lymphadenectomy was noninferior to open D2 with lower complication rates, faster recovery, and comparable relapse-free survival. This trial established laparoscopic D2 as an acceptable alternative in experienced East Asian centers. JCOG0501 (2021) explored whether neoadjuvant chemotherapy before D2 gastrectomy improved outcomes for type 4 or large type 3 gastric cancer; neoadjuvant S-1/cisplatin did not demonstrate a survival benefit, confirming D2 gastrectomy with adjuvant therapy as the standard.
Integration into clinical practice guidelines and recommendations
D2 lymphadenectomy without pancreaticosplenectomy is now the recommended standard for curative-intent gastrectomy worldwide, based on the 15-year Dutch trial data and consistent East Asian outcomes. Laparoscopic D2 is accepted at experienced centers.
D2 dissection standard for cT2-T4 gastric cancer; laparoscopic approach acceptable at experienced centers
Now
Current standard of care and ongoing research directions
D2 lymphadenectomy without pancreaticosplenectomy is the global standard for curative gastric cancer surgery. The 15-year Dutch trial data confirmed its oncologic superiority when performed safely. Laparoscopic and robotic D2 are increasingly adopted, with KLASS-02 providing randomized support. Active research explores the role of para-aortic (D2+) dissection, sentinel node navigation, and the integration of neoadjuvant chemotherapy/immunotherapy with definitive surgery.
Why did the view on D2 lymphadenectomy change over time?+
Initial results from the 1995 Dutch trial showed D2 had higher mortality (10% vs 4%) and morbidity (43% vs 25%). However, the 15-year follow-up (2010) revealed that D2 reduced locoregional recurrence and gastric cancer-specific death. The initial excess mortality was attributed to the learning curve and routine pancreaticosplenectomy, which was subsequently abandoned. Asian centers consistently achieved D2 mortality of 2-3%, confirming the procedure was safe in experienced hands.
Can D2 lymphadenectomy be done laparoscopically?+
KLASS-02 (1,050 patients) demonstrated that laparoscopic D2 lymphadenectomy was noninferior to open D2 for locally advanced gastric cancer, with lower complication rates and equivalent relapse-free survival. This trial was performed in experienced Korean centers, and laparoscopic D2 is now accepted in guidelines for centers with appropriate expertise.
