Background
Phase III RCT (Dutch D1/D2 Trial). 996 patients in 80 Dutch hospitals with resectable gastric cancer randomized to limited D1 vs extended D2 lymph node dissection. D2 dissection includes perigastric nodes plus hepatoduodenal, celiac, and splenic nodes; standard in Japan but untested in Western populations. All surgeons trained by a Japanese expert and monitored during the trial.
Interventions and follow up
Arm A: D2 lymph node dissection — perigastric + hepatoduodenal + left gastric + celiac + splenic artery/hilum nodes; includes splenopancreatectomy as required
Arm B: D1 lymph node dissection — perigastric nodes only
Primary endpoint: Overall survival
mFollow up: 5 years (initial report); 15-year follow-up published separately (Songun 2010)
Arm B: D1 lymph node dissection — perigastric nodes only
Primary endpoint: Overall survival
mFollow up: 5 years (initial report); 15-year follow-up published separately (Songun 2010)
Results
5-year OS: 47% (D2) vs 45% (D1) — not significant (95% CI for difference: -9.6% to +5.6%)
Postoperative complications: 43% (D2) vs 25% (D1), P<.001
Postoperative mortality: 10% (D2) vs 4% (D1), P=.004
5-year cumulative relapse (R0 patients, excluding postop deaths): 37% D2 vs 43% D1
Postoperative complications: 43% (D2) vs 25% (D1), P<.001
Postoperative mortality: 10% (D2) vs 4% (D1), P=.004
5-year cumulative relapse (R0 patients, excluding postop deaths): 37% D2 vs 43% D1
Adverse events
Main adverse events: D2 substantially increased morbidity and postoperative mortality in Dutch centers, largely attributable to routine splenopancreatectomy (performed in 30% of D2 patients). Hospital stay: 16 vs 14 days median.
Conclusions
In Dutch hospitals, D2 dissection offered no OS benefit over D1 at 5 years and significantly increased perioperative morbidity and mortality. However, this result reflected Western learning curve issues (splenopancreatectomy contributing to mortality) rather than the superiority of D1; later analyses (Bonenkamp 1999, Songun 2010 15-year data) showed D2 reduced locoregional recurrence and cancer-specific death when perioperative mortality was excluded.
Key Limitations
Key Limitations: Western surgeons had limited D2 experience despite instruction; the high D2 mortality (10%) likely reflects a learning curve, not an inherent risk of the procedure. Routine splenopancreatectomy in the D2 arm contributed substantially to morbidity. Japanese single-institutional D2 series report <1% mortality, suggesting the Dutch results reflect implementation rather than the procedure itself. At 15-year follow-up, D2 showed lower cancer-related deaths (Songun 2010).
Clinical Context
The Dutch D2 trial and its 15-year follow-up (Songun 2010) collectively support D2 dissection as the surgical standard for resectable gastric cancer — but only when performed in experienced centers. Modified D2 without routine splenopancreatectomy substantially reduces morbidity. Current international guidelines (ESMO, NCCN) recommend D2 lymphadenectomy at experienced centers for potentially curative gastric cancer surgery.
References