Endoscopic histological validation of clinical complete response after neoadjuvant chemoimmunotherapy for esophageal cancer

Neoadjuvant chemotherapy combined with immunotherapy can significantly shrink tumors and regress metastatic lymph nodes, ^1​ increasing the rate of clinical complete response (cCR) in esophageal cancer and providing new approaches for esophageal-preserving minimally invasive therapy. ^2​ We report a case of locally advanced esophageal squamous cell carcinoma in which, after neoadjuvant chemoimmunotherapy, imaging assessment indicated the cCR, but endoscopic mucosal suspicious lesions prompted endoscopic submucosal dissection (ESD) for pathological verification.

A 68-year-old man presented with progressive dysphagia. Gastroscopy revealed a cauliflower-like lesion in the mid-esophagus, 28–36 cm from the incisors ( Fig. 1a ), and biopsy showed poorly differentiated squamous cell carcinoma. Positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced chest CT revealed multiple metastatic lymph nodes in the mediastinum and hepatic hilum ( Fig. 1b ). The patient refused surgery. After multidisciplinary team (MDT) discussion, a neoadjuvant regimen was administered: six cycles of nab-paclitaxel plus cisplatin and sintilimab, followed by one cycle of sintilimab combined with S-1 maintenance therapy. Follow-up PET showed that the metabolic activity of the primary lesion and metastatic lymph nodes had almost disappeared ( Fig. 1c ), and the imaging assessment indicated the cCR. The patient was planned for watchful waiting.

Fig. 1.

Comparison before and after neoadjuvant therapy. ( a ) Gastroscopy before neoadjuvant therapy showing a cauliflower-like lesion in the esophagus. ( b ) PET/CT before neoadjuvant therapy showing a mid-esophageal lesion with multiple metastatic lymph nodes in the mediastinum and hepatic hilum. ( c ) Follow-up PET/CT after neoadjuvant therapy showing the near-complete disappearance of hypermetabolic activity in the esophageal lesion and lymph nodes. ( d ) Follow-up gastroscopy after neoadjuvant therapy showing the patchy roughness in the esophagus.

On follow-up magnifying endoscopy with narrow-band imaging, multiple rough and scarred mucosal areas were observed in the esophagus ( Fig. 1d ), with IPCL patterns mainly type B1, suggesting residual low-grade and high-grade intraepithelial neoplasia. After MDT discussion, ESD was performed to clarify the pathological response status of the esophageal lesion and achieve resection ( Fig. 2a–e , Video 1​ ). Postoperative pathology revealed chronic esophagitis with low-grade and a small amount of moderate-to-severe dysplasia ( Fig. 2f ); both lateral and basal margins were negative for carcinoma, indicating the pathological complete response (pCR). No postoperative complications occurred, and the patient was discharged with a regular follow-up.

Fig. 2.

Endoscopic procedure and postoperative pathology. ( a ) After iodine staining, patchy lightly stained and unstained areas were visible. ( b ) Circumferential marking of the lesion with an electrocautery knife. ( c ) Circumferential mucosal incision after submucosal injection. ( d ) The wound bed after the complete en bloc resection of the lesion. ( e ) The gross specimen after resection. ( f ) Postoperative pathology showing moderate-to-severe dysplasia (HE, ×20).

Video 1 Endoscopic histological validation of the clinical complete response after neoadjuvant chemoimmunotherapy for esophageal cancer.

Download video file ^{(53.5MB, mp4)}

Post-neoadjuvant fibrotic changes increase the difficulty of imaging assessment, raising the question of whether imaging-based cCR truly indicates oncological clearance. For patients who refuse surgery, relying solely on imaging for watchful waiting carries a non-negligible risk of occult residual disease. ^3​ In contrast, en bloc endoscopic resection can provide more complete pathological information than multiple biopsies, obtaining large specimens with minimal trauma while simultaneously resecting the lesion, thereby achieving organ preservation. The “resection-diagnosis” strategy proposed in this case accomplishes both lesion resection and pathological verification, confirming the pCR while preserving the esophageal function, offering a feasible decision-making pathway for similar patients. Of course, the long-term oncological safety still requires prospective studies and the long-term follow-up.

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Informed Consent

Written informed consent was obtained from the patient to publish these images and video.