Immune-Related Esophagitis and Durable Response to Second-Line Treatment With Nivolumab in Stage IV Squamous Cell Esophageal Carcinoma

Sep 28, 2026

Immune checkpoint inhibitors such as nivolumab improve outcomes in advanced cancers but can trigger immune-related adverse events, including rare upper gastrointestinal toxicities. Isolated immune-mediated esophagitis is uncommon, particularly in esophageal squamous cell carcinoma, and its clinical significance is not well defined. This case describes a 78-year-old man developing ulcerative esophagitis after starting nivolumab, with infection excluded. Nivolumab was stopped and treated with proton pump inhibitors and high-dose corticosteroids, leading to symptom improvement and sustained tumor regression.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Introduction

Esophageal cancer burden and ICI role

Mechanism and evidence for nivolumab in ESCC

Immune-related adverse events and diagnostic approach

Case Presentation

Review began 11/13/2025 Review ended 11/26/2025 Published 12/02/2025 © Copyright 2025 Meneses et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CCBY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98324 Open Access Case Report Immune-Related Esophagitis and Durable Response to Second-Line Treatment With Nivolumab in Stage IV Squamous Cell Esophageal Carcinoma Olga Meneses 1, Maria Alzamora 2, Carla Dias 2, Raquel Ortigão 3, Dânia Marques 1 1. Medical Oncology, Portuguese Institute of Oncology Francisco Gentil, Porto, PRT 2. Pathology, Portuguese Institute of Oncology Francisco Gentil, Porto, PRT 3. Gastroenterology, Portuguese Institute of Oncology Francisco Gentil, Porto, PRT Corresponding author: Olga Meneses, [olga.dulce.9@gmail.com](olga.dulce.9@gmail.com) Abstract Immune checkpoint inhibitors such as nivolumab have transformed the management of advanced cancers but may lead to immune-related adverse events, including rare toxicities affecting the upper gastrointestinal tract. Isolated immune-mediated esophagitis is uncommon, particularly in esophageal squamous cell carcinoma, and its clinical implications remain poorly characterized. We report the case of a 78-year-old male with advanced esophageal squamous cell carcinoma who developed epigastric pain, dysphagia, and weight loss seven months after initiating nivolumab therapy. Endoscopy revealed ulcerative esophagitis, and histology confirmed chronic inflammation, with infectious etiologies ruled out. Nivolumab was discontinued, and the patient was managed with proton pump inhibitors and high-dose corticosteroids, resulting in significant symptom improvement. At the time of immunotherapy discontinuation, the patient had achieved a radiologic partial response. Remarkably, during follow-up without further oncologic therapy, his disease continued to regress, culminating in a complete response that has been sustained for twenty-one months. This case is notable for the unique combination of advanced esophageal squamous cell carcinoma, isolated nivolumab-induced esophagitis, and a durable tumor response sustained long after immunotherapy discontinuation, underscoring the importance of recognizing immune-mediated toxicities and their potential association with robust antitumor activity. Categories: Oncology, Gastroenterology Keywords: complete response, esophageal squamous cell carcinoma, esophagitis, immune-related adverse effects, nivolumab Introduction Esophageal cancer represents a major global health concern. In 2020, more than 600,000 cases and 540,000 deaths were reported worldwide [1,2] . Esophageal squamous cell carcinoma (ESCC) constitutes the predominant histological subtype. In response to this disease burden, immune checkpoint inhibitors (ICIs) have emerged as key therapeutic options. Reflecting these advancements, current European Society of Medical Oncology guidelines recommend immunotherapy regimens for advanced ESCC, including nivolumab as monotherapy or in combination with chemotherapy, or ipilimumab and pembrolizumab for programmed death-ligand 1 (PD-L1)-positive tumors in selected patients. These recommendations apply to both first-and second-line settings, depending on PD-L1 expression [3] . Nivolumab is a fully human IgG4 monoclonal antibody that targets programmed cell death protein 1 (PD-1), thereby restoring anti-tumor immunity by blocking PD-1/programmed death-ligand 1 (PD-L1) interactions and reactivating T-cell responses. Its efficacy in previously treated advanced ESCC is supported by the phase 3 ATTRACTION-3 trial, which demonstrated improved overall survival compared with chemotherapy (median OS 10.9 vs 8.4 months; HR 0. 77), although progression-free survival was shorter (1 .7 vs 3.4 months) [4] . Despite their efficacy, ICIs

FAQs

What condition developed after starting nivolumab in this case?

The patient developed isolated immune-mediated esophagitis with ulcerative esophagitis on endoscopy.

How was infectious or other causes evaluated?

Endoscopy and histology confirmed chronic inflammation and infectious etiologies were ruled out.

What treatment was given after discontinuing nivolumab, and what was the outcome?

Nivolumab was discontinued and the patient received proton pump inhibitors and high-dose corticosteroids, with significant symptom improvement and a durable tumor response that progressed to complete response sustained for twenty-one months.

Sep 28, 2026

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