The quest for the optimal treatment approach for localized esophageal cancer has been ongoing for decades. More than 30 years ago, the initial approach involved surgical resection alone, but this yielded dismal outcomes with 5-year overall survival rates no greater than 10%.1 In light of these poor outcomes, the addition of radiotherapy to surgical resection was explored in early studies, indicating a promising benefit.2 Ultimately, a randomized phase 3 clinical trial evaluating the combination of chemotherapy and radiotherapy vs radiotherapy alone, without surgery, in patients with either squamous cell carcinoma (86%) or adenocarcinoma of the esophagus was conducted.3 Patients treated with a combination of fluorouracil and cisplatin with 5000 cGy of radiotherapy showed a significant improvement in overall survival, as well as both local and distant recurrence rates, compared with patients receiving 6400 cGy of radiotherapy alone (2-year survival rate, 50% vs 33%; P < .001). Despite these benefits, chemoradiotherapy came with a cost of increased toxic effects, with 44% of patients experiencing severe adverse effects and 20% of patients experiencing life-threatening adverse effects compared with 25% and 3% in patients receiving radiotherapy alone. Long-term follow-up of this study showed continued superiority for nonsurgical combined modality therapy,4 laying the groundwork for use of bimodality therapy over radiotherapy alone, which is a treatment strategy that has persisted into regimens used today.
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Eads JR, Haller DG. Primary Chemoradiotherapy for Older Patients With Esophageal Cancer. JAMA Oncol. 2021;7(10):1451–1452. doi:10.1001/jamaoncol.2021.2668
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