(159) The Comparative Effectiveness of Trimodal Therapy Versus Definitive Chemoradiation in Older Adults with Locally Advanced Esophageal Cancer

Publication Number: 833

Background: The comparative effectiveness of trimodal therapy versus definitive chemoradiation for older adults with locally advanced esophageal cancer is uncertain. Only two randomized trials have considered this comparison, and older adults and patients with adenocarcinomas were underrepresented in these studies.

Objectives: To determine the comparative effectiveness of trimodal therapy versus definitive chemoradiation in older adults with locally advanced esophageal cancer, accounting for immortal time bias with a novel method.

Methods: A US cohort of adults 66-79 years of age diagnosed with incident locally advanced esophageal cancer between 2004 and 2017 was identified using the Surveillance Epidemiology and End Results-Medicare database. Eligible individuals were required to have a Charlson Comorbidity Score ≤5 and a Kim frailty index ≤0.35. We used observational data to emulate a hypothetical trial comparing trimodal therapy and definitive chemoradiation and used the clone-censor-weight analytic technique to avoid immortal time bias. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home.

Results: The study population included 1,240 individuals with adenocarcinomas and 661 with squamous cell carcinomas. Amongst older adults diagnosed with adenocarcinomas, the five-year risk of mortality was 73.4% (95% CI: 69.1 – 77.4) in the trimodal therapy group and 83.8% (95% CI: 78.6 – 87.2) in the definitive chemoradiation group (RR= 0.88, 95% CI: 0.82 – 0.95). Amongst older adults diagnosed with squamous cell carcinomas, the five-year risk of mortality was 62.6% (95% CI: 50.9 – 73.5) in the trimodal therapy group and 72.3% (95% CI: 67.6 – 76.3) in the definitive chemoradiation group (RR= 0.87, 95% CI: 0.70 – 1.01). The one-year risk of functional adverse events was higher in the trimodal therapy group for patients with adenocarcinomas (RR= 1.40, 95% CI: 1.22 – 1.65) and squamous cell carcinomas (RR= 1.21, 95% CI: 1.00 – 1.49). The five-year mean cumulative count of healthy days at home was higher in the trimodal therapy group (840 days, 95% CI: 780 – 902) than the chemoradiation group (680 days, 95% CI: 635 – 762) for patients with adenocarcinomas (difference= 160, 95% CI: 67 – 229); for patients with squamous cell carcinomas, the count was higher for trimodal therapy (990 days, 95% CI: 866 – 1,126) than chemoradiation (813 days, 95% CI: 750 – 884) (difference= 177, 95% CI: 51 – 313).

Conclusions: Trimodal therapy was associated with lower mortality than definitive chemoradiation. The benefits were smaller than suggested by prior observational studies that were limited by immortal time bias. These findings can be used with clinical expertise and patient preferences to enhance shared decision-making.