Early Brain Metastasis despite Pathological Complete Response after Radical Resection for Esophageal Cancer following Chemotherapy and Pembrolizumab

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INTRODUCTION: Brain metastasis from esophageal cancer is rare. In particular, recurrent brain metastasis following multimodal treatment, such as preoperative chemotherapy and surgical resection, is extremely uncommon.We present a case of early brain metastasis from esophageal cancer despite achieving pathological complete response (pCR). CASE PRESENTATION: A middle-aged man presented with dysphagia. Upper gastrointestinal endoscopy revealed stenosis caused by an ulceroinfiltrative tumor located in the middle of the thoracic esophagus. Targeted biopsies confirmed squamous cell carcinoma. Contrast-enhanced CT revealed circumferential, irregular wall thickening with contrast enhancement, showing infiltration into the left main bronchus and enlarged lymph nodes in the paraesophageal and the left supraclavicular regions. The diagnosis was middle thoracic esophageal squamous cell carcinoma cT3br N2M0 cStage IIIB (according to the Japanese Classification of Esophageal Cancer, 12th Edition). The patient underwent chemotherapy, including 5-fluorouracil, cisplatin, and pembrolizumab, as the combined positive score exceeded 10. Following this chemotherapy with an immune checkpoint inhibitor, the tumor had regressed, and targeted biopsies revealed no malignant findings. The post-chemotherapy diagnosis was ycT3rN0M0 ycStage II, and the patient subsequently underwent thoracoscopic esophagectomy. Surgical findings showed no evidence of tumor infiltration. Postoperative histopathological examination showed no residual tumor cells in either the esophagus or resected lymph nodes, corresponding to histological response of grade 3. However, the patient presented with depression 2 months after the surgery, and abnormal behavior was shown 3 months after the surgery. Although cranial CT and MRI revealed ring-enhancing lesions in the right cerebellar hemisphere and the right frontal lobe, there was no recurrence or metastasis other than in the brain. The patient underwent resection of the frontal lobe tumor and was diagnosed with brain metastasis of esophageal cancer. Stereotactic radiation therapy and pembrolizumab were started; however, the patient died 5 months after esophagectomy due to brain metastasis progression. CONCLUSIONS: 5-Fluorouracil and cisplatin plus pembrolizumab therapy may allow conversion surgery in advanced esophageal cancer. However, even in patients who achieve pCR at the primary lesion, brain metastasis may occur after surgical treatment. Preoperative and postoperative surveillance for brain metastases is necessary in patients at high risk of distant metastasis, even if the local lesion is controlled.

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