Incomplete neoadjuvant chemo(radio)therapy negatively impacts pathological response and overall survival in locally advanced esophageal cancer

Background: Neoadjuvant chemoradiation (nCRT) and resection is one treatment option for esophageal and gastroesophageal junction cancer. In some patients, the full chemotherapy regimen is not completed. We assessed the association between incomplete administration of neoadjuvant chemo(radiation) and pathological response (pCR) and overall survival (OS) in esophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). Methods: Patients with OAC and OSCC treated with nCRT and esophagectomy diagnosed in 2015–2022 were identified from the Netherlands Cancer Registry. The association of pCR with any change in the chemotherapy was assessed using multivariable logisitic regressions. Kaplan-Meier method and Cox regression models were used to investigate OS and to adjust for confounding variables. Results: 3340 patients with OAC and 685 patients with OSCC were included. In OAC, in 10 % (n = 323) the chemotherapy was administered incomplete. This was associated with a significantly lower odds for pCR compared to complete chemotherapy (15 % vs 21 %, adjusted OR, 0.69; 95 % CI, 0.30–0.79; p = 0.026). In OSCC this association was not found (adjusted OR, 1.31; 95 % CI, 0.82–2.10; p = 0.267). OAC patients with incomplete chemotherapy had a worse median OS (31.8 months vs 42 months; adjusted HR: 1.26; 95 % CI: 1.08–1.46) compared to patients who received complete chemotherapy. In OSCC this difference in median OS (85.6 months vs 57.2 months; adjusted HR: 1.16; 95 % CI: 0.83–1.60) was not observed. Conclusion: This nationwide study demonstrates that incomplete administration of chemotherapy in the nCRT scheme is associated with worse oncologic outcomes in patients with OAC.