This multicenter European cohort study (14 centers, 2018–2024) compared overall survival, disease-free survival, and recurrence patterns in 297 patients with esophageal or gastroesophageal junction adenocarcinoma who achieved pathological complete response (pCR) after either perioperative FLOT chemotherapy (n=147) or CROSS chemoradiotherapy (n=150) followed by curative esophagectomy.
After multivariable adjustment, FLOT was independently associated with better overall survival (HR 0.34; 95% CI 0.16–0.69; P=.003) and disease-free survival (HR 0.35; 95% CI 0.19–0.62; P<.001) vs CROSS. Recurrence rates were 8.8% (FLOT) vs 24.7% (CROSS), and median time to recurrence was longer after FLOT (16.8 vs 12.8 months).
- Retrospective cohort design with inherent selection bias; FLOT patients were younger and more often node-positive at baseline, despite multivariable adjustment. - pCR rate and definition may vary across 14 centers without central pathology review. - Post-recurrence treatments were not reported, which could confound survival differences.
Among esophageal adenocarcinoma patients who achieve pCR, those treated with perioperative FLOT have markedly lower recurrence rates and better survival than those treated with CROSS — suggesting that pCR should not be viewed as equivalent across neoadjuvant regimens. Clinicians should interpret pCR outcomes in the context of the specific treatment strategy used.
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