Oesophageal cancer is the eighth most common malignancy and among the leading causes of cancer-related mortality globally, with marked geographic variation in incidence, histological subtype, and outcome [1-3]. Countries with a lower Human Development Index, including India, continue to report a disproportionately high burden of squamous cell carcinoma, in contrast to the rising predominance of adenocarcinoma in high-income settings [1,2]. Reported five-year survival rates range widely from 5% to 30%, reflecting differences in stage at presentation, treatment access, and standard of care [4].

For patients with locally advanced, non-metastatic disease who are ineligible for or decline surgical resection, definitive chemoradiotherapy (dCRT) delivered to 50.4-54 Gy in 1.8 Gy fractions with concurrent platinum-taxane chemotherapy represents the accepted curative-intent standard [5]. While landmark trials such as RTOG 85-01 and the CROSS trial have established the survival benefit of combined-modality therapy over radiotherapy or surgery alone [6,7], much of this evidence derives from Western cohorts with a high proportion of adenocarcinoma and access to surgical salvage. Data describing long-term survival after dCRT in squamous-predominant, resource-constrained settings remain comparatively sparse.

Beyond survival, treatment-related and disease-related morbidity meaningfully shapes the survivorship experience. Radiation-induced oesophagitis, stricture formation requiring dilatation, persistent dysphagia, fistula formation, and secondary pulmonary complications can substantially impair health-related quality of life (HRQoL), even among patients who achieve durable disease control [8,9]. Systematic, patient-reported assessment using validated instruments such as the EORTC QLQ-OES18 module is therefore essential to fully characterise treatment outcomes, yet such data are infrequently reported alongside survival outcomes in the same cohort, particularly from South Asian populations.

This study addresses this gap by concurrently evaluating (i) long-term survival outcomes and (ii) patient-reported HRQoL and symptom burden in a cohort of patients with oesophageal cancer treated with curative-intent dCRT at a tertiary cancer centre in South India. We hypothesised that, consistent with global reports, a meaningful proportion of patients would achieve durable disease control, and that persistent symptom burden among survivors would be dominated by upper gastrointestinal and reflux-type symptoms rather than severe dysphagia, reflecting functional recovery of swallowing after treatment completion.

Objectives:

1. To determine the survival outcomes and identify prognostic factors affecting survival among adult patients with histologically confirmed, non-metastatic oesophageal cancer treated with curative-intent definitive radiotherapy, with or without concurrent chemotherapy, at the Department of Radiation Oncology, NIMS, between January 2014 and June 2022.
2. To assess the health-related quality of life among disease-free survivors of non-metastatic oesophageal cancer following curative-intent definitive radiotherapy, with or without concurrent chemotherapy, using a validated quality-of-life questionnaire.

2.1 Study Design and Setting This was an observational, cross-sectional study conducted in the Department of Radiation Oncology, Nizam's Institute of Medical Sciences (NIMS), Hyderabad, India, between June 2023 and June 2024. The study was approved by the NIMS Institutional Ethics Committee (Review Letter No. EC/NIMS/3204/2023) and conducted in accordance with Good Clinical Practice guidelines of the Central Drugs Standard Control Organization and the Indian Council of Medical Research ethical guidelines for biomedical research involving human subjects. Written informed consent was obtained from all patients who participated in the HRQoL assessment component. 2.2 Study Population Two linked patient populations were defined corresponding to the two study objectives. Survival analysis: All adult patients with histologically confirmed, non-metastatic oesophageal cancer who completed curative-intent definitive radiotherapy, with or without concurrent chemotherapy, in the Department of Radiation Oncology, NIMS, between January 2014 and June 2022, were eligible. Patients who did not complete the planned radiotherapy course, who had disease recurrence prior to definitive radiotherapy, or who underwent surgery or neoadjuvant chemotherapy prior to radiotherapy were excluded. HRQoL analysis: Patients from the survival cohort who remained disease-free on follow-up and provided informed consent were eligible for HRQoL assessment. Patients unable to comprehend or complete the study questionnaire, or with recurrent/metastatic disease at the time of assessment, were excluded. Of 40 patients meeting eligibility criteria, complete follow-up and questionnaire data were obtained for 30 survivors. 2.3 Treatment Protocol All patients received definitive radiotherapy to a dose of 50.4-54 Gy delivered in 25-28 fractions of 1.8 Gy. Concurrent chemotherapy, where administered, consisted of weekly carboplatin and paclitaxel, in keeping with institutional standard practice for definitive chemoradiotherapy in oesophageal cancer. 2.4 Data Collection Demographic characteristics, comorbidities, tumour histology and location, staging investigations, treatment delivery details, and follow-up outcomes were abstracted retrospectively from patient records for the survival cohort. For the HRQoL cohort, data were collected prospectively at a single cross-sectional timepoint using the EORTC QLQ-OES18, a validated 18-item, disease-specific module assessing dysphagia, eating restriction, reflux, pain, and swallowing-related symptoms, scored on a four-point Likert scale (not at all/a little/quite a bit/very much). To maximise comprehension and response validity, the questionnaire was administered in English, Hindi, or Telugu according to patient preference. 2.5 Statistical Analysis Overall survival was defined as the time from diagnosis to death from any cause, and disease-free survival as the time from diagnosis to disease recurrence or death, whichever occurred first; both were estimated using the Kaplan-Meier method, with patients alive and disease-free at last follow-up censored. Descriptive statistics (frequencies, percentages, medians with ranges) were used to summarise baseline characteristics and HRQoL symptom severity. Analyses were performed using Microsoft Excel 2019 (Microsoft Corporation) and SPSS Version 22.0 (IBM Corporation).

3.1 Baseline Patient and Disease Characteristics

Seventy-six patients with non-metastatic oesophageal cancer treated with curative-intent definitive radiotherapy between January 2014 and June 2022 were included in the survival analysis. The median age at diagnosis was 55 years (range, 20-80 years), with the largest proportion of patients in the 50-59-year age band (30%, n=23). The cohort was 52% female (n=40) and 47% male (n=36). A substantial proportion of patients had a history of tobacco use (71%, n=54) and coexisting hypertension (71%, n=54) or diabetes mellitus (68%, n=52). Squamous cell carcinoma was the predominant histology (93%, n=71), with adenocarcinoma comprising the remainder (7%, n=5). The tumour was most frequently located in the middle third of the oesophagus (45%, n=34), followed by the lower third (42%, n=32) and upper third (13%, n=10). Concurrent chemotherapy was delivered alongside radiotherapy in 86% (n=65) of patients.

Table 1. Baseline demographic and clinicopathological characteristics (N = 76)

Figure 1. Age distribution of patients at diagnosis (N = 76).

3.2 Survival Outcomes

At a median follow-up of 34 months, the median overall survival was 32 months and median disease-free survival was 29 months (Kaplan-Meier estimates). Five-year OS and DFS were 41% and 40%, respectively. At last follow-up, 39% (n=30) of patients were alive, 57% (n=44) had died, and 2% (n=2) were lost to follow-up. Among deaths, 90% (n=40) were attributable to cancer progression and 9% (n=4) to non-cancer causes. Local recurrence occurred in 22% (n=17) of patients and distant recurrence in 9% (n=8); one patient (1%) underwent salvage treatment. Among survivors, 9% (n=7) were alive with local recurrence and 2% (n=2) alive with distant recurrence.

Table 2. Survival and recurrence outcomes at median follow-up of 34 months

Figure 2. Kaplan-Meier estimate of overall survival.

Figure 3. Kaplan-Meier estimate of disease-free survival.

3.3 Health-Related Quality of Life

HRQoL was assessed in 30 disease-free survivors using the EORTC QLQ-OES18. Overall, symptom burden was mild in the majority of respondents. The most frequently reported symptoms were acid indigestion/heartburn and acid regurgitation into the mouth, each reported by 21% (n=6) of survivors, followed by difficulty with solid food intake (17%, n=5), early satiety (14%, n=4), and dry mouth (14%, n=4). Choking, difficulty eating, cough, and pain on eating were each reported by 7% (n=2) of patients, while swallowing difficulty with saliva, eating in front of others, and enjoyment of meals were each affected in 3% (n=1) of patients. Notably, the large majority of survivors (90%) tolerated solid and liquid food without substantial difficulty, and no patient reported severe or very severe symptoms across any domain assessed.

Table 3. Prevalence of key symptoms reported on the EORTC QLQ-OES18 among survivors (n = 30)

Figure 4. Prevalence of key symptoms reported on the EORTC QLQ-OES18 among disease-free survivors (n = 30).

In this cohort of 76 patients with predominantly squamous cell, non-metastatic oesophageal cancer treated with curative-intent definitive chemoradiotherapy at a South Indian tertiary centre, median overall and disease-free survival were 32 and 29 months respectively, with a 5-year overall survival of 41%. These figures compare favourably with historical benchmarks for definitive chemoradiotherapy reported in Western trials of predominantly resectable or borderline-resectable disease, such as RTOG 85-01, in which combined-modality therapy achieved a 5-year OS of 27% [6], and are broadly consistent with contemporary series in squamous-predominant Asian populations. This suggests that carefully delivered definitive chemoradiotherapy can achieve durable disease control even in resource-constrained settings and in the context of a squamous-predominant, often locally advanced disease profile. The pattern of failure observed - local recurrence in 22% versus distant recurrence in 9% - underscores that local-regional control remains the dominant challenge after definitive chemoradiotherapy, consistent with prior reports identifying loco-regional relapse as the principal mode of treatment failure in non-surgically managed oesophageal cancer [21,24]. This pattern reinforces the ongoing rationale for treatment intensification strategies, adaptive radiotherapy, and dose-escalation approaches balanced carefully against toxicity, as demonstrated by the absence of survival benefit with dose escalation beyond 50.4 Gy in RTOG 94-05 [13]. A key strength of this study is the concurrent evaluation of patient-reported HRQoL using a validated, disease-specific instrument in survivors from the same treatment cohort. Contrary to an intuitive expectation that dysphagia would dominate the survivorship symptom profile, we found that the most prevalent persistent symptoms were reflux-type (acid indigestion/heartburn and acid regurgitation, each 21%) rather than mechanical dysphagia; severe or very severe symptoms were not reported in any domain, and 90% of survivors tolerated oral intake without substantial difficulty. This finding aligns with prior longitudinal HRQoL studies demonstrating that acute treatment-related dysphagia and odynophagia typically resolve within 4-8 weeks of completing chemoradiotherapy, with physical functioning and swallowing-related domains returning towards baseline thereafter [16,18]. The relatively favourable functional profile observed in our survivors may reflect a survivorship-bias effect inherent to cross-sectional assessment of disease-free patients, as well as genuine late functional recovery. These findings carry direct clinical implications. The prominence of reflux-type symptoms suggests that survivorship care pathways for oesophageal cancer should incorporate proactive management of gastro-oesophageal reflux - including acid-suppressive therapy and dietary counselling - alongside routine surveillance for stricture and recurrence. The relatively low prevalence of severe dysphagia in long-term survivors is reassuring but should not obscure the acute morbidity experienced during treatment, nor the substantial nutritional and functional impact reported in other cohorts during the peri-treatment period [22]. A comprehensive, multidisciplinary survivorship model - integrating radiation oncology, nutrition, gastroenterology, and psychosocial support - is therefore warranted to optimise both disease control and lived quality of life. Our results should be interpreted within the context of several limitations. First, the retrospective ascertainment of survival data and the single-institution design may limit generalisability and introduce selection or information bias. Second, the HRQoL assessment was cross-sectional and confined to 30 of an intended 40 eligible survivors, reflecting attrition through loss to follow-up and mortality; this relatively small sample constrains the precision of symptom prevalence estimates and precludes longitudinal or multivariable analysis of predictors of poor HRQoL. Third, the absence of baseline (pre-treatment) HRQoL data precludes direct assessment of within-patient change over time. Finally, as an inherently selected population of disease-free survivors, our HRQoL findings cannot be generalised to patients with active or recurrent disease, who likely experience a distinct and more severe symptom burden [19]. Future prospective, multicentre studies incorporating longitudinal HRQoL assessment from baseline through survivorship, alongside biomarker and radiomic correlates of treatment response, would help to refine risk stratification and personalise both oncological and supportive care strategies for this population.

Definitive chemoradiotherapy delivered with curative intent achieves durable disease control in a substantial proportion of patients with predominantly squamous cell oesophageal cancer treated in a South Asian tertiary care setting, with a 5-year overall survival of 41%. Among disease-free survivors, persistent symptom burden was dominated by manageable reflux-type symptoms rather than severe dysphagia, indicating meaningful functional recovery after treatment completion. These findings support the incorporation of routine, validated patient-reported outcome assessment into standard survivorship care for oesophageal cancer and highlight local-regional recurrence as the principal target for future treatment intensification strategies.

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Ethics approval: NIMS Institutional Ethics Committee, Review Letter No. EC/NIMS/3204/2023.

Conflicts of interest: The authors declare no conflicts of interest.

Funding: No external funding was received for this study.