Impact of PD-1 and PD-L1 inhibitors on patient-reported outcomes in esophageal squamous cell carcinoma: a systematic review of clinical trials.

Abstract

Esophageal squamous cell carcinoma (ESCC) carries a poor prognosis and is associated with symptoms such as dysphagia that substantially impair patients' health-related quality of life (HRQoL). The combination of chemotherapy with an immune checkpoint inhibitor is widely used in real-world practice and is a recommended treatment for unresectable, recurrent, or metastatic ESCC. This systematic literature review assessed patient-reported outcomes (PROs) in clinical trials evaluating PD-1/PD-L1 inhibitors in ESCC. A comprehensive search of PubMed, Embase, and the Cochrane Library, supplemented by Elicit, was conducted to identify clinical trial publications reporting PROs in ESCC patients treated with PD-1/PD-L1 inhibitors. Eligible studies were published through July 20, 2025, and were included if they met the following criteria: (1) enrolled ESCC patients; (2) reported PROs, including HRQoL, in randomized clinical trials of PD-1/PD-L1 inhibitors; and (3) were published in English. Thirteen clinical trial publications met the inclusion criteria. Investigated agents included nivolumab, tislelizumab, camrelizumab, sintilimab, and pembrolizumab. PROs were measured using the EORTC QLQ-C30 and QLQ-OES18, EQ-5D-5L, EQ-5D-3L, and FACT-E questionnaires, with follow-up ranging from 8 to 60 weeks. The EORTC QLQ-C30 and QLQ-OES18 were the most frequently used instruments. While results varied by treatment and setting, PD-1/PD-L1 inhibitor-based regimens generally maintained or improved PROs compared with chemotherapy, including overall HRQoL and esophageal cancer-specific symptoms such as pain, reflux, and eating and swallowing difficulties. Across trials, PD-1/PD-L1 inhibitors were associated with maintenance or improvement in PROs compared with chemotherapy in ESCC, especially in global health status, functional domains, and key ESCC-related symptoms.