Transitioning from neoadjuvant chemoradiation to perioperative chemotherapy for esophageal adenocarcinoma: Impact on...

Treatment of esophageal adenocarcinoma has historically involved trimodality therapy. Recently, perioperative chemotherapy has become standard of care due to improved survival. We investigated the implications of this change on surgical and pathologic outcomes.

This multicenter retrospective analysis included adults who underwent esophagogastrectomy for esophageal/gastroesophageal junction adenocarcinoma between 2023 and 2025. The primary outcome was any positive margin on final pathology. Secondary outcomes included rates of nodal upstage and posttreatment tumor characteristics. Fisher exact and Kruskal-Wallis tests were used for comparisons.

In total, 110 patients were included; 22 received perioperative chemotherapy (20.0%), 48 chemoradiation (chemoRT, 43.6%), and 40 induction chemotherapy followed by chemoRT (chemo + chemoRT, 36.3%). On final pathology, 36.4% of patients experienced nodal upstaging in the chemotherapy group (n = 8) relative to 16.7% (n = 8) and 7.5% (n = 3) in the chemoRT and chemo + chemoRT groups (P = .030). Similarly, more patients had tumors exhibiting poor treatment response (tumor regression grade 3) in the chemotherapy group (n = 7, 33.3%) compared with the other 2 groups (n = 2 [4.5%] and n = 4 [10.5%]; P = .007). More patients in the chemotherapy group had any positive final margin (n = 8, 36.4%), as compared with the chemoRT (n = 5, 10.4%) or chemo + chemoRT groups (n = 4, 10.0%; P = .017). Early data suggest greater rates of frozen-to-final esophageal margin discrepancies in the chemotherapy cohort (n = 2 [16.6%] vs n = 1 [2.8%] chemoRT vs n = 2 [6.6%] chemo + chemoRT; P = .232).

In this small multi-institutional study, chemotherapy-only preoperative regimens seemed to be associated with increased rates of nodal upstage and margin positivity after esophagectomy relative to radiotherapy-inclusive protocols.