Catastrophic Esophageal Tumor Perforation within One Week after First-Line Chemo-Immunotherapy for Advanced...

Esophageal perforation secondary to advanced esophageal squamous cell carcinoma (ESCC) is a life-threatening oncologic emergency that can rapidly progress to mediastinitis, empyema, and septic shock. With the increasing use of first-line chemo-immunotherapy, early tumor necrosis-particularly in ulcerated or deeply invasive lesions-may precipitate catastrophic perforation.

A man in his 70s was diagnosed with unresectable middle thoracic ESCC with distant metastases to the iliopsoas muscle and left supraclavicular lymph node (cT3brN2M1b, cStage IVB). First-line cisplatin plus 5-fluorouracil combined with pembrolizumab was initiated. On day 6 of cycle 1, he developed sudden, severe chest pain. CT revealed pneumomediastinum extending to the anterior mediastinum with periesophageal fluid collection; pleural effusion was minimal at presentation. Esophageal tumor perforation with mediastinitis was diagnosed, and broad-spectrum antibiotics and ventilatory support were started. Emergent endoscopy confirmed the perforation, and a covered self-expandable metallic stent was deployed. Right pleural drainage yielded grossly contaminated effusion, and the patient deteriorated to septic shock. In the ICU, aggressive source control was pursued with 3 pleural lavage and drainage procedures within the first 2 weeks (1 thoracoscopic and 2 open thoracotomy procedures). Although sepsis was controlled and his general condition temporarily improved after multimodal source control, systemic anticancer therapy could not be resumed. This clinical course underscores that even an ultra-early perforation during first-line chemo-immunotherapy can critically disrupt subsequent oncologic management, highlighting the need for rapid diagnosis, aggressive source control, and early goals-of-care discussions in unresectable disease.

Tumor-related esophageal perforation can occur as early as day 6 during first-line chemo-immunotherapy for unresectable ESCC and may rapidly progress to fulminant mediastinitis and empyema. Once perforation is suspected, prompt diagnosis and an integrated, multidisciplinary, multimodal source-control strategy-endoluminal sealing with a covered stent plus timely and adequate thoracic drainage/lavage-should be prioritized, underscoring the clinical significance of ultra-early onset during the initial treatment period in the context of prior reports.