Adding anti-PD-1 antibody to definitive chemoradiotherapy in elderly patients with esophageal squamous cell carcinoma: higher intensity does not equate to better outcomes.

[BACKGROUND AND PURPOSE] The benefit of adding anti-PD-1 antibodies to definitive chemoradiotherapy (dCRT) in elderly patients with esophageal squamous cell carcinoma (ESCC) remains uncertain. This study evaluated its efficacy and safety versus dCRT alone.

[MATERIALS AND METHODS] We retrospectively analyzed the patients aged ≥ 70 years with ESCC treated at three academic centers from 2009 to 2023. All patients received first-line dCRT and the study group additionally received anti-PD-1 antibodies (IO group). Propensity score matching (PSM) was applied to balance baseline factors.

[RESULTS] A total of 241 patients were enrolled, including 130 in the IO group and 111 in the dCRT group. After 1:1 PSM (110 patients per group), no significant differences in overall survival (OS) or progression-free survival (PFS) were observed. The median OS was 34.5 vs 33.7 months (HR = 0.86, 95%CI: 0.58-1.28,  0.467) and median PFS was 29.8 vs 17.8 months (HR = 0.79, 95%CI: 0.55-1.13,  0.194). Multivariate Cox analysis identified high nutritional risk as an independent predictor of worse OS ( = 0.014), while both advanced TNM stage ( = 0.030) and high nutritional risk ( = 0.016) were independently associated with shorter PFS. Subgroup analyses suggested that patients with good performance, better nutritional status or lower comorbidity burden may benefit from combination therapy. Grade 3-4 adverse events were comparable between two groups.

[CONCLUSION] Adding anti-PD-1 antibodies to dCRT did not result in a significant improvement in OS or PFS in the ESCC patients aged ≥ 70 years; however exploratory findings indicate a potential PFS signal in selected patients with favorable baseline conditions, which requires confirmation in prospective studies.