In this large, population-based study, patterns of treatment and outcomes of elderly patients with potentially curable EC were comprehensively analyzed. The results showed that the usage ratios of surgery were reduced with the increase in age, CRT was mostly adapted in patients with locally advanced-stage EC, and RT alone was also employed, especially in patients aged ≥ 80 years. The survival analysis indicated that all the treatment patterns had survival benefits in elderly patients compared to Obs. The use of surgery was associated with improved OS in all older age groups, and CRT was superior to RT or CT alone. The results were stable across subgroup analyses stratified by most factors, including sex, clinical stage, histological subtype, and tumor location, demonstrating the reliability of our conclusions.
In younger patients, surgery-based trimodality therapy has been the standard treatment for locally advanced EC[19, 20]. However, elderly patients tend to have a decline in physiological function and a high prevalence of chronic diseases, such as high blood pressure, diabetes, and cardiovascular system diseases, which make them difficult to respond to surgical trauma and recover slowly. Elderly patients undergoing esophagectomy for cancer are reported to have a significantly higher risk of postoperative mortality, especially in patients aged 75 years or older[22–24]. Hence, elderly patients with EC should be cautiously evaluated and selected for surgery. In fact, only one-third of patients in our cohort underwent surgical resection, and the number of patients who underwent surgery decreased dramatically with increasing age. In this study, a significantly small number of patients (< 10%) aged > 80 years underwent surgery, reflecting concerns about postoperative morbidity and the underuse of surgery in elderly patients with EC.
In the survival analysis, elderly patients who underwent surgery lived significantly longer than those who received other treatment patterns, including CRT. The advantage of surgery was stable in both EAC and ESCC and across stages I to III. At the same time, other retrospective studies have supported the use of surgery in elderly patients with EC, and esophagectomy was found to be associated with improved survival, even with increased risk of complications in elderly patients with EC[6, 10, 11, 26, 27]. In fact, it is reported that trimodality therapy is also an acceptable treatment option for properly selected elderly patients with EC. In addition to these findings, our study showed that the survival benefit of surgery can be observed even in patients aged > 80 years, whereas the benefit was comparable with that of CRT among elderly patients aged 85 years and over. Therefore, after comprehensive assessment and rigid screening, surgical treatment with or without neoadjuvant treatment should be preferentially recommended for elderly patients with good performance status and long expected life span, as the same treatment pattern for young patients, given the improved outcomes with treatment. For patients intolerable to surgery or aged > 80 years, radical RT can be considered as an alternative option.
Considering postoperative morbidity and reduced quality of life, a large proportion of patients with EC favor non-operative treatment patterns. In our analysis, almost half of the patients selected CRT as their primary treatment, and 22% of patients aged 85 years and over received RT alone. In the survival analysis, the survival benefit of CRT was only next to surgery and superior to RT or CT alone. CRT has been the standard therapy for patients with locally advanced EC ineligible for surgery since the Radiation Therapy Oncology Group 85 − 01 trial, and no patients survived for 5 years in the RT alone group. However, in clinical practice, due to concerns regarding treatment-related adverse effects, including esophagitis, pneumonitis, and hematologic toxicity, several elderly EC patients only undergo RT alone[30, 31]. Several previous studies have demonstrated that CRT might be considered as both effective and safe in elderly patients with EC, exhibiting similar long-term clinical benefits compared to younger patients[32–34]. Our study confirmed the superiority of CRT over RT alone among all elderly age groups in a large population. RT alone should be recommended with caution even in the eldest group (aged > 85 years). If patients cannot tolerate doublet CT combined with RT, single-drug oral CT drugs can be considered, such as S1, Xeloda, and other fluorouracil analogues[12, 35].
Our study has the following strengths. First, our study used a population-based database with a large sample size and long-term follow-up period. Second, a comprehensive analysis of primary treatment patterns and wide-ranging subgroup analysis stratified by age, which made the conclusion reliable and stable, were performed in our study. However, our study has several limitations. First, as with any retrospective study, selection bias and unmeasured confounding variables are inevitable, and the baseline characteristics of patients in different patterns were not well balanced, which reflected real-world treatment choices. Second, some information was missing on patient characteristics and treatment processes in the SEER database, such as performance status, CT regimens, and comorbidities, which limited the multivariate Cox regression analysis. Additionally, for study endpoints, data regarding recurrence and metastasis information were unavailable.
Given the natural limitations of retrospective studies, the findings of our study should be interpreted with caution in clinical practice. As described in the limitations of our study, selection bias should be considered. When selecing the optimal treatment pattern for elderly patients with EC, their physical conditions should be comprehensively assessed, including nutritional status, cardiopulmonary function, and associated underlying diseases. If possible, a comprehensive geriatric assessment (CGA) is recommended, which has been increasingly involved in guiding treatment decisions for elderly cancer patients. In younger patients with high CGA scores, more aggressive treatment options, such as surgery combined with neoadjuvant CRT, may be considered as the first option. For patients with higher age (aged ≥ 85 years) or poor general condition or unsuitable for surgery (regardless of medical reasons), CRT was the preferred treatment pattern. For patients with poor health, palliative RT for local tumors combined with supportive nutrition treatment might extend the survival of patients and improve their quality of life.