The North American Experiences

Esophageal squamous cell carcinoma (ESCC) remains a globally prevalent malignancy with distinct epidemiological patterns, aggressive tumor biology, and complex therapeutic considerations. In North America, its incidence has declined, yet it continues to pose a significant clinical challenge due to frequent late-stage presentation and aggressive biology. This chapter outlines a comprehensive, stage-specific approach to the diagnosis, treatment, and surveillance of ESCC, incorporating the latest evidence and evolving practices in molecular profiling, endoscopic therapy, multimodal treatment, immunotherapy, and surgical innovation. Early stage ESCC is increasingly managed with endoscopic resection techniques such as endoscopic mucosal resection and endoscopic submucosal dissection, offering curative outcomes in appropriately selected patients. For locoregionally advanced disease, neoadjuvant chemoradiation followed by esophagectomy remains the standard of care, with high rates of pathologic complete response and durable survival. Definitive chemoradiation is a viable alternative in nonoperative candidates, offering a potentially curative, organ-sparing alternative. The role of salvage esophagectomy is discussed with attention to its elevated risks and the importance of selective application. Minimally invasive esophagectomy has enabled adherence to oncologic principles with reduced perioperative morbidity, while adjuvant immunotherapy has emerged as a potential therapeutic advance in patients with residual disease. For metastatic disease, frontline treatment now includes chemoimmunotherapy or dual immunotherapy regimens, guided by PD-L1 status and patient characteristics. Surveillance strategies are currently individualized based on stage and treatment modality, while circulating tumor DNA is an emerging tool for early recurrence detection and treatment response monitoring. Quality of life and survivorship are increasingly prioritized, with recognition of the long-term physical, nutritional, and psychosocial sequelae of both surgical and nonsurgical therapies. This chapter emphasizes the importance of multidisciplinary care, patient-centered decision-making, and ongoing innovation to improve both survival and quality of life in ESCC management.