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Primary Therapy: Relapse Patterns after “Curative Resection”

Local regrowth or failure in the tumor bed and regional lymph nodes, or distant failures via hematogenous or peritoneal routes are all common mechanisms of failure after “curative resection” in clinical,121,122 reoperative,13,123 and autopsy123-126 series. For lesions of the GEJ, both the liver and lungs are common sites of hematogenous spread. With gastric lesions that do not extend to the esophagus, the initial site of hematogenous spread is usually the liver, and many relapses could be prevented if an effective “abdominal” therapy could be combined with treatment of the primary tumor and regional lymph nodes.

Local-regional failures occur commonly within the region of the gastric bed and nearby lymph nodes (Table 75-4). Tumor relapse in anastomoses, the gastric remnant, or the duodenal stump is also frequently seen. In a University of Minnesota reoperative analysis,13,123 local-regional failure occurred as the only evidence of relapse in 29% of the 86 patients with relapse (23% of the 105 evaluable patients at risk) and as any component of failure in 88%. More extensive operative procedures including routine splenectomy, omentectomy, and radical lymph node dissection neither improved survival127 nor decreased the incidence of local or regional regrowth in the reoperative analysis.13,123 Subsequent relapse within the scope of the initial node dissection occurred in a high percentage of the patients even when radical node dissections were performed (removal of N1, N2, and sometimes N3 nodes; E-Table 75-3).123,128 This indicates the difficulty of obtaining a complete lymph node excision encompassing this anatomic location and provides a partial explanation for the lack of survival benefit with a D2 versus D1 node dissection in phase III trials previously discussed.75-78,129 In a more recent clinical analysis of patterns of relapse from Memorial Sloan Kettering Cancer Center, 50% of patients with relapse had a local-regional component.122

Patterns of failure by stage were analyzed in detail in a series of 130 patients who underwent resection performed with curative intent at the Massachusetts General Hospital (MGH).121 Local-regional failure occurred as any component of failure in 49 patients (38%) and as the sole failure in 21 (16% of 130 patients at risk and 24% of the 88 patients with disease progression). The incidence of localregional failure by stage was in excess of 35% for T3N0, T4N0, T3N1–3, and T4N1–3 lesions. The sites at highest risk for localregional failure included the gastric bed (27 of 130 patients, 21%) and the anastomosis or gastric remnant (33 of 130 patients, 25%). The true incidence of gastric bed, regional lymph node, and peritoneal failures may be higher, because this was neither a reoperative nor an autopsy series (see comparative findings in Table 75-4 and E-Table 75-3). Some additional information on patterns of relapse by stage exist in both the University of Minnesota reoperation analysis13,123 and the University of Washington autopsy analysis.126 Although patterns of failure data are more accurate in such analyses, patient selection is biased.

The above studies demonstrate significant relapse rates at local, regional, and distant sites following surgical resection alone. This emphasizes and supports the need for multimodality therapy in patients with locally advanced gastric cancers.