Dear Editor, We read with interest the recent phase III multicenter randomized clinical trial by Li et al evaluating fibrin sealant (FS) for prophylaxis of cervical anastomotic leakage (AL) after McKeown esophagectomy for esophageal or esophagogastric junction cancer1. In 360 patients from six centers, the incidence of AL within 3 months was 7.3% in the FS group and 13.3% in the control group, but the primary endpoint did not reach conventional statistical significance1. This trial addresses an important clinical problem, as cervical AL remains one of the most consequential complications after esophagectomy2. However, several issues deserve clarification. First, interpretation should remain anchored to the primary analysis. Although FS was associated with a numerically lower AL rate, the overall result was statistically negative1. Therefore, the study should be interpreted as suggesting a possible benefit rather than establishing efficacy. The subgroup result in patients undergoing upfront surgery should also be treated cautiously. As Sun et al emphasized, subgroup findings are most credible when they are prespecified, supported by formal interaction testing, and interpreted with restraint in the context of multiple comparisons3. Otherwise, they are better regarded as hypothesis generating than practice changing. Second, more granular reporting of the leakage outcome would strengthen the clinical relevance of the findings. AL is not a uniform complication: minor leaks managed conservatively differ substantially from leaks requiring drainage, reoperation, or prolonged hospitalization. Since the overall incidence of postoperative complications was similar between the two groups1, readers would benefit from knowing whether FS influenced the severity, timing, or management burden of AL rather than only the overall event count. Such information is important when judging whether a numerical reduction in AL translates into meaningful patient benefit. Third, the external validity of the findings should be interpreted carefully. All patients underwent McKeown esophagectomy with circular-stapled cervical anastomosis across six centers in China1. The applicability of these results to hand-sewn anastomoses, linear-stapled techniques, or different perioperative pathways therefore remains uncertain. In addition, earlier single-center retrospective evidence suggested a more favorable effect of FS4, highlighting that the magnitude of benefit may vary according to patient selection, surgical technique, and institutional practice. In summary, PLACE030 is a timely randomized trial that provides more rigorous evidence than prior retrospective studies1,4. However, because the primary endpoint was not statistically significant, and because the subgroup finding should be viewed as exploratory, routine prophylactic use of FS after McKeown esophagectomy cannot yet be considered established. Further studies with clearer reporting of leak severity and clinically relevant downstream consequences would help define whether selected patients may still benefit from this approach.
Yang et al. (2026) studied this question.