Brain metastases from esophageal cancer: a phenomenon of adjuvant therapy?

BACKGROUND: Brain metastases from esophageal cancers are uncommon, yet our impression was that they occurred more frequently than expected after esophagectomy plus adjuvant therapy. Therefore, we determined (1) incidence and prevalence of, risk factors for, and survival after development of brain metastases following esophagectomy for esophageal cancer, and (2) their association with adjuvant therapy.
METHODS: From 1985 to 2002, 403 patients (52%) underwent esophagectomy alone and 369 esophagectomy plus adjuvant therapy (118 [15%] preoperative only, 124 [16%] postoperative only, and 127 [16%] both). Hazard-function methodology was used to characterize time-related occurrence of brain metastases and risk factors. Inferences were confirmed by propensity analysis.
RESULTS: Twenty-nine patients developed brain metastases, 20 within 1 year; 6 had undergone surgery alone, and 23 had adjuvant therapy. Prevalence was 2.5% 5 years after surgery alone, but 8.4%, 7.0%, and 18.4% after preoperative adjuvant therapy only, postoperative adjuvant therapy only, and both, respectively (p < 0.0001). Greater number of locoregional lymph node metastases was associated with brain metastases after surgery alone (p = 0.04). Distant metastases (p = 0.03) and both preoperative and postoperative adjuvant therapy (p = 0.004) were risk factors. Median survival after diagnosis of brain metastases was 3.5 months. Postesophagectomy propensity-matched survival was shorter after adjuvant therapy than after surgery alone; thus, time available for developing brain metastases after surgery alone was slightly lower.
CONCLUSIONS: A dose-related increased incidence of brain metastases after adjuvant therapy for esophageal cancer cannot be explained by increased longevity. Adjuvant therapy itself, not just advanced disease, appears to create conditions conducive to developing these rapidly fatal metastases.