Definitive Chemoradiotherapy versus Trimodality Therapy for Locally Advanced Esophageal Adenocarcinoma: A Multi-Institutional Retrospective Cohort Study

Simple Summary: The combination of chemoradiotherapy followed by surgery (trimodality therapy) is considered standard of care for patients with locally advanced esophageal adenocarcinoma, but many potential candidates for surgery receive curative-intent chemoradiotherapy alone. This study compared the outcomes of patients who received trimodality therapy to those who received curative-intent chemoradiotherapy. Our primary analysis found that trimodality therapy reduced the risk of local tumor recurrences, but we did not detect statistically significant differences in the risks of distant metastases or mortality. These results can help patients and clinicians make informed treatment decisions, although further studies are needed to refine our understanding of the trade-offs between the two treatment strategies. The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.