Beyond recurrence: Late relapses and second primary tumors after curative esophagectomy

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INTRODUCTION: The majority of recurrences after esophagectomy occur within the first two years. In France, postoperative follow-up usually continues for five years. However, later relapses have been reported, raising the question of whether prolonged follow-up is indicated. METHODS: A retrospective, two-center study was conducted at the University Hospital of Lille and Saint-Antoine Hospital in Paris. The study included patients who had undergone curative esophageal cancer surgery between 2009 and 2015, and were alive and free of recurrence at five years. Late recurrences (≥5 years) and second primary cancers were identified and their associated factors analyzed. RESULTS: Of 664 patients who underwent resection of esophageal cancer, 229 met the inclusion criteria. Twelve of these patients (5.2%) experienced a late recurrence, 50% of which were metastatic, occurring up to 107 months after surgery. In multivariable analysis, five variables were independently associated with decreased recurrence-free survival: male sex (OR=6.09; P=0.001), prior cancer history (OR=2.28; P=0.048), neoadjuvant chemoradiotherapy (OR=3.18; P=0.002), squamous cell carcinoma (OR=2.22; P=0.022), and positive-margin resections (OR=56.32; P=0.001). Sixteen patients (6.9%) developed a second primary cancer, mainly head and neck or lung cancer. Neoadjuvant chemoradiotherapy was associated with an increased risk of a second cancer site (OR=2.64; P=0.011). CONCLUSION: A residual risk of disease progression persists beyond five years after curative esophagectomy, in the form of late recurrences (5%) and second primary cancers (6.9%). These findings challenge the systematic discontinuation of follow-up at five years and support a prolonged and individualized surveillance strategy.