Beyond survival: understanding long-term quality of life after esophageal cancer treatment

Assessing quality of life (QoL) in patients with esophageal cancer is vital for patients and clinicians, as it offers key insights into the benefits and harms of different treatment options beyond just survival rates. Accurate and reliable QoL assessment is relevant for clinical decision-making and a critical aspect of the informed consent process. As esophageal cancer is often detected at an advanced stage only about one-third of patients are diagnosed with localized disease that may be curable (1). Given the overall poor survival rate, QoL considerations become particularly significant in cases where the benefits of treatment are marginal (2). In patients with locally advanced esophageal cancer, advancements in surgical techniques, neoadjuvant therapies, and the centralization of multidisciplinary care teams have led to improved five-year survival rates (3). With the growing number of long-term survivors, the discussion around long-term QoL has become increasingly important. Several predictive modelling tools have been developed for assessing prediction of morbidity, mortality and long-term survival of patients undergoing curative-intent treatment of esophageal cancer (4-6). However, despite a growing body of literature related to patient-reported outcomes and QoL metrics, there is a paucity of predictive tools available to clinicians to support decision-making and patient communication concerning QoL (7-10). Such tools may help identify individuals at higher risk of experiencing a decline in QoL and provide targeted support to improve functional outcomes and well-being in the months and years after treatment.

Chen and colleagues examined the QoL trajectory in 363 esophageal cancer survivors’ post-treatment, using the European Quality of Life 5-Dimensions (EQ-5D-3L) questionnaire to measure health across five dimensions (11). Patients, treated with surgery, endoscopic intervention, or chemoradiotherapy, were compared to a baseline QoL established from over 25,000 non-cancer individuals matched by age, sex, and location. The study, involving data from the Endoscopic Screening for Esophageal Cancer in China (ESECC) trial and a medical insurance database for rural residents in China, aimed to model post-treatment QoL for improved clinical decision-making. Their analysis revealed that QoL declined post-treatment, particularly within the first year. Patients undergoing chemoradiotherapy experienced the greatest initial decline (37.8%) but showed the fastest recovery, while those treated surgically had a smaller decline (12.2%), and endoscopic treatment showed the least impact (7.5%). Across all treatments, QoL improved to near baseline within five years. Treatment type emerged as the sole significant factor affecting long-term QoL, highlighting the need for tailored care, especially for symptoms of pain or discomfort.

The authors should be commended for identifying and addressing several limitations in the present scientific literature regarding QoL assessment in patients with esophageal cancer. Firstly, this study distinguishes itself through the inclusion of patients who underwent endoscopic treatment and chemoradiotherapy for esophageal cancer, whereas prior QoL research has largely focused on patients who underwent esophagectomy. Notably, there is a lack of evidence regarding QoL assessment after endoscopic interventions for esophageal cancer (12,13). By broadening the scope to include these patient groups, the study captures a wider range of outcomes, offering insights into the QoL of those undergoing different therapeutic approaches. This is important because non-surgical treatments are increasingly used, particularly for patients who are not candidates for surgery or prefer less invasive options.

Additionally, the authors have opted to administer the EQ-5D-3L—a general health-related QoL questionnaire—as opposed to the more commonly used EORTC-QLQ-C30 or disease-specific QoL questionnaires such as the EORTC-QLQ-OES-18 developed by the European Organization for Research and Treatment of Cancer (EORTC) or Functional Assessment of Cancer Therapy Esophageal cancer subscale (FACT-E) (7-9,12). While these validated questionnaires have been extensively applied to investigate QoL after treatment for esophageal cancer, they have been criticized by some to be lengthy and burdensome for use in clinical practice. Furthermore, these questionnaires are not designed for use in disease-free survivorship, when the nature of symptoms and their effect on QoL may differ from those experienced during diagnosis and treatment (10). In that sense a general health questionnaire such as the EQ-5D-3L, which contains five health state dimensions assessed over five questions and divided into only three levels (no problems, some problems, and extreme problems), may prove easier to administer whilst allowing for a holistic assessment, incorporating mental health, and permitting the estimation of quality-adjusted life years (QALYs); a metric that is valuable in cancer trials, screening projects, and health economics (14).

While the study contributes valuable data to the literature, several methodological limitations should be addressed to better interpret its findings and broader applicability. The most significant shortcoming of the study design is the absence of individual baseline QoL data for most esophageal cancer survivors. The authors recognise this and utilise surrogate data from residents in the same community to calibrate a pre-treatment baseline. However, even when carefully matched, this may fail to capture personal health histories, pre-existing conditions, or specific QoL factors unique to each patient. This is particularly relevant when trying to provide more nuanced and granular explanations for statistical relationships observed within the study such as the significant decline in QoL noted in patients undergoing chemoradiotherapy for esophageal cancer. Although the authors demonstrated that the average difference between surrogate and actual baseline data for a small subset of patients was below the minimally clinically important difference, the reliance on community-level data limits the validity of the study’s QoL assessments.

The study’s use of the EQ-5D-3L, a general health-related QoL tool also raises some concerns. Although the EQ-5D-3L is a validated measure of well-being, it does not capture the range of disease-specific symptoms that are important for comprehensive evaluation of esophageal cancer survivors’ QoL, such as symptoms of dysphagia, reflux or nutritional concerns. By not incorporating esophageal cancer disease-specific QoL instruments—such as with the EORTC QLQ-OES-18—the study risks overlooking critical aspects of recovery and survivorship. This is particularly relevant for long-term survivors, whose experience of living with the after-effects of cancer treatment may differ greatly from the general health concerns measured by the EQ-5D-3L. Additionally, the authors highlight the utility of the EQ-5D-3L questionnaire in identifying the presence of anxiety and depression in esophageal cancer survivors. Whilst anxiety and depression are the most common mental health disorders in esophageal cancer patients, research by Bouras et al. would suggest a strong correlation between the presence of certain post-operative symptoms such as pain, dumping syndrome and loss of appetite with an increased risk of postoperative anxiety or depression (15). These findings are further reinforced through the outcomes of The Lasting Symptoms after Esophageal Resection (LASER) study, which through a large prospective European cohort, identified that physical symptoms such as pain related to thoracic scars following esophagectomy were associated with a significant decline in health-related QoL. The LASER study also developed a clinical symptom-based tool; however, further external validation is required particularly amongst non-European cohorts to evaluate its wider clinical utility and validity (10). Subsequently with consideration of the existing literature, administering disease-specific QoL assessments alongside general questionnaires offers a more comprehensive and meaningful evaluation of a patient’s overall health, which is crucial for delivering targeted support and optimizing care. Another notable limitation of the EQ-5D-3L is that it assesses health dimensions over only three levels. This limited scale may not be sensitive enough to capture more subtle variations in symptom severity or changes in a patient’s QoL over time, which would be particularly useful when comparing QoL between different therapeutic approaches.

The study’s rural setting in China raises questions regarding the broader applicability of its findings, particularly to Western cohorts. Although the authors cross-referenced their predicted QoL outcomes with data from multicentre studies in China, the United States, and the United Kingdom, the generalizability of these results beyond this specific context remains limited (16,17). Cultural differences, healthcare infrastructure, and treatment accessibility significantly influence patients’ QoL outcomes, and these factors vary greatly across geographic and socio-economic environments. Furthermore, demographic, histopathological, and comorbidity variations between East Asian populations and those in North America and Northern Europe must be considered. For instance, esophageal cancer patients in these regions tend to present with a higher prevalence of comorbidities, such as obesity and are generally older at diagnosis. In this study, the peak age of included participants was 76, which is lower than what is typically seen in Northern Europe (18,19). Additionally, esophageal adenocarcinoma is more prevalent in Western populations, whereas squamous cell carcinoma is more common in East Asia, and these subtypes require different treatment approaches (20). Moreover, key determinants that could influence QoL, such as the presence of comorbidities, operative techniques, neoadjuvant therapy, tumour grade and post-operative complications were not adequately addressed or identified in this study. Assessing pre-operative comorbidities and the histopathological stage is valuable when considering QoL after therapeutic interventions, as demonstrated by Djärv et al. who reported that preoperative comorbidity negatively impacts post-esophagectomy physical and role functions and exacerbates symptoms such as fatigue in patients with advanced esophageal cancer tumour stages (21). Similarly, Derogar et al. note that the presence of major postoperative complications also has significant effects on both short and long-term QoL and may be independent predictors of poor QoL in long-term survivors after esophagectomy (22). Finally, the authors have not reported whether neoadjuvant therapy was administered prior to patients undergoing surgery, which is an important consideration as other investigations have shown higher global health status scores in patients receiving and completing neoadjuvant treatment than surgery alone (12). These variables are crucial for understanding long-term QoL outcomes and developing accurate models that predict QoL and should be accounted for in future analyses to ensure more comprehensive and generalizable conclusions.

Chen et al. report an initial decline in QoL after esophageal cancer treatment, with levels gradually returning to near baseline—a temporal pattern supported in some literature (23,24). However, well-designed studies like LASER, using more comprehensive QoL assessment, indicate specific symptoms can persist long after treatment (10). This discrepancy likely reflects a limitation in methodology, as a general QoL questionnaire may miss enduring, treatment-related effects. Furthermore, several methodological limitations affect the generalizability and applicability of their investigation and subsequently their QoL predictive tool. External validation in other populations is needed before considering its use in real-world clinical settings. Future research should prioritize validating these predictive models across diverse populations, incorporating disease-specific QoL assessments, and addressing clinical variables such as comorbidities and postoperative complications.

With an increasingly frail and elderly population, this topic has never been more critical for those involved in esophageal cancer management. Among patients undergoing curative therapy, surgical resection is likely to have the most substantial impact on long-term QoL. Consequently, organ-sparing strategies, such as active surveillance in patients with a complete pathological response to neoadjuvant therapies, may offer a valuable approach for maintaining QoL in this vulnerable cohort (25).

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Esophagus. The article has undergone external peer review.

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-24-25/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-24-25/coif). B.K. serves as an unpaid editorial board member of Annals of Esophagus from December 2023 to November 2025. The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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