Korean J Intern Med > Volume 40(2); 2025 > Article
Hyung: Treatment strategies for octogenarians with esophageal cancer: changing age-based treatment paradigms
The therapeutic landscape of esophageal cancer has undergone a remarkable evolution over recent decades, with multimodal approaches, including neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, becoming standard options for locally advanced disease [1]. Concurrent with these therapeutic advances, we are witnessing a significant demographic shift in the patient population, with an increasing proportion of older adult patients diagnosed with esophageal cancer [2]. This demographic transition poses unique challenges in treatment decision-making, particularly for patients aged 80 years and older, where the delicate balance between treatment efficacy and tolerability becomes increasingly complex and crucial for optimal outcomes. This shift reflects improved life expectancy in the general population and changes in risk factor profiles. Therefore, understanding treatment outcomes in this growing older adult population has become increasingly critical for clinical decision-making and healthcare resource allocation.
Ryu et al. [3] provided valuable insights into the treatment outcomes of octogenarians with esophageal cancer, challenging a few of our preconceptions regarding age-based treatment decisions. The investigators discussed a comprehensive comparison of treatment outcomes between patients aged ≥ 80 years and their younger counterparts while examining the impact of different treatment modalities within the older adult cohort. This multifaceted analysis allowed for a nuanced understanding of age-related differences and the impact of treatment selection on the older adult population.
Several key findings of this study warrant careful consideration. As expected, octogenarians demonstrated higher rates of comorbidities and poorer performance statuses than younger patients. This resulted in a natural selection bias toward nonsurgical approaches, particularly CRT or radiotherapy (RT) alone. However, the most striking observation was that while treatment outcomes showed a trend toward inferior results in the older adult cohort compared to the younger population, the differences were modest, particularly in the CRT/RT group. Furthermore, compared to untreated octogenarians, those who received treatment with curative intent demonstrated significantly superior survival outcomes, albeit with the important caveat that treated patients were generally more fit with fewer comorbidities.
The implications of these findings for surgical management warrant particular attention. While the current study suggests comparable outcomes with surgical intervention in octogenarians (n = 7), this must be interpreted within the broader context of existing literature and real-world clinical experience. Previous meta-analyses and large-scale retrospective studies from the United States have demonstrated increased postoperative complications in older adult patients, with significant implications for both short-term recovery and long-term quality of life [4,5]. Moreover, the comparable survival outcomes between surgery and CRT/RT among the older adult population in this study suggest that many octogenarians prefer nonsurgical approaches, particularly given their potential impact on functional status and independence.
The tolerability of concurrent CRT is another crucial consideration that requires careful examination. While the outcomes were generally comparable to those of younger patients, previous studies have highlighted the increased risk of radiation pneumonitis in older adult patients [6,7]. Certain evidence suggests that paclitaxel-containing regimens may be associated with a higher risk of pneumonitis, warranting careful evaluation of chemotherapy choices and potentially suggesting the need for alternative regimens in older adult patients [8]. In addition, the risk of cytopenia and infection with reduced functional reservoirs in this population necessitates careful consideration of chemotherapy selection and dosing strategies.
The question of RT alone versus concurrent CRT is another decision-making point in older adult patient care. While a few clinicians might be tempted to omit chemotherapy in older adult patients to reduce cytotoxic chemotherapy-related toxicity, data from the Japanese national registry have demonstrated inferior survival with RT alone compared to CRT, even in patients aged ≥ 80 years [9]. This finding suggests that carefully selected older adult patients may benefit from combined-modality therapy, highlighting the importance of appropriate patient selection rather than age-based treatment decisions.
Modern older adult patient assessment approaches have evolved significantly, moving beyond the traditional chronological age and performance status measures. The emerging field of geriatric oncology has introduced sophisticated evaluation tools to better predict treatment tolerance and outcomes. The comprehensive geriatric assessment encompasses multiple domains, including functional status, cognitive function, nutritional status, social support, and detailed comorbidity evaluation [10]. The Clinical Frailty Scale provides a standardized approach for assessing physiological reserves. When used in collaboration with geriatric medicine specialists, these tools may provide a more nuanced and reliable means of determining treatment appropriateness than traditional metrics alone.
Therefore, treatment modification strategies should be considered for older adult patients. Dose reduction, altered fractionation schedules, and careful selection of chemotherapy regimens may play a role in optimizing outcomes for this population. The potential role of newer targeted therapies and immunotherapy in older adult patients with appropriate molecular profiles should be considered in the future, as these treatments may offer alternative options with different toxicity profiles. Quality of life considerations are particularly important in older adult patients, where treatment decisions must balance potential survival benefits with functional independence and overall well-being. Future research should incorporate quality of life metrics and patient-reported outcomes as primary endpoints, particularly when comparing different treatment modalities in older adult populations. These findings suggest a paradigm shift from age-based treatment decisions toward more individualized approaches based on functional status, comorbidity burden, and formal frailty assessments. This allows the delivery of meaningful cancer therapy to appropriately select older adult patients while avoiding excessive treatment-related morbidity in more vulnerable individuals.
The development of older adult-specific clinical trials is another crucial requirement in this field. Traditional clinical trials often exclude or underrepresent older patients, leading to a paucity of high-quality evidence. Dedicated trials focusing on older adult patients with appropriate endpoints and toxicity assessments could provide valuable guidance for clinical decision-making. Recently, a phase 1 trial of definitive concurrent chemoradiation with paclitaxel in older adult patients with esophageal squamous cell carcinoma was reported to have an acceptable safety profile [11].
In conclusion, this study provides encouraging evidence that appropriately selected octogenarians can achieve meaningful benefits from curative-intent treatment of esophageal cancer. The challenge of moving forward lies in optimizing patient selection and treatment modifications to maximize benefits while minimizing toxicity in this vulnerable population. Future research should focus on developing better assessment tools and treatment strategies tailored to older patients, ultimately leading to more personalized and effective care for this patient population.

Notes

Conflicts of interest
The author discloses no conflicts.
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