Adenocarcinoma of the esophagus and gastroesophageal junction: The evolving treatment landscape for locally advanced and metastatic disease in the era of immune checkpoint inhibitors and biomarker‐driven therapeutics

This patient is a man aged 55 years with a past medical history significant for hypertension, hyperlipidemia, post-traumatic stress (PTS) disorder, opioid use disorder on maintenance therapy, and tobacco dependence.He presented to the emergency department in 2023 with progressive dysphagia to solid food over 3 months.He did not report hematemesis, respiratory difficulties, or weight loss.His Eastern Cooperative Oncology Group performance status was 0. A complete metabolic profile and blood count were normal.He underwent urgent esophagogastroduodenoscopy, which revealed a near complete obstructing esophageal mass at the gastroesophageal junction (GEJ), extending proximally 5 cm into the distal esophagus; biopsy confirmed a moderately differentiated adenocarcinoma (Figure 1).The tumor was negative for human epidermal growth factor receptor 2 (HER2/neu), mismatch-repair (MMR) proteins were intact (not shown), and programmed cell death ligand-1 (PD-L1) was detectable with a combined positive score (CPS) of 5-9 (Figure 1).Staging computed tomography (CT) scan of the neck, chest, abdomen, and pelvis revealed nodular thickening of the GEJ and upper abdominal lymphadenopathy, with gastrohepatic nodes measuring up to 1 cm, prominent nodes adjacent to the gastric cardia, and a nonspecific, prominent, subcentimeter left periaortic node; there was no definitive evidence of distant metastases.On subsequent endoscopic ultrasound (EUS), the tumor was staged as clinical stage T3 and N2 (cT3N2) by sonographic criteria.Subsequent fluorodeoxyglucose-positron emission tomography (PET)/CT revealed a hypermetabolic distal esophageal GEJ (E/GEJ) mass as well as hypermetabolic upper abdominal and left axillary lymph nodes (Figure 2A,B).Biopsy of the left axillary node showed reactive lymphoid tissue in the setting of recent coronavirus disease vaccination.He underwent staging laparoscopy, which showed no evidence of occult peritoneal carcinomatosis.Thus the final clinical stage was cT3N2M0 stage III adenocarcinoma of the GEJ according the American Joint Committee on Cancer (AJCC) 8th Edition clinical staging system for esophageal and GEJ adenocarcinoma.After consultation with thoracic surgery and a multidisciplinary gastrointestinal tumor board discussion, the consensus was to proceed with curative-intent trimodality treatment with neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy.