Evaluation of tumor regression by neoadjuvant chemotherapy regimens for esophageal adenocarcinoma: a systematic review and meta-analysis

Locally advanced esophageal adenocarcinomas (EACs) are treated with multimodal therapy, namely surgery, neoadjuvant chemotherapy (NAC) or chemoradiotherapy (CRT) depending on patient and tumor level factors. Yet, there is little consensus on choice of the optimum systemic therapy. To compare the pathological complete response (pCR) after FLOT, non-FLOT-based chemotherapy and chemoradiotherapy regimes in patients with EACs. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. Studies were included if they had investigated the use of chemo(radio)therapy regimens in the neoadjuvant setting for EAC and reported the pCR rates. A meta-analysis of proportions was performed to compare the pooled pCR rates between FLOT, non-FLOT and CRT cohorts. We included 22 studies that described tumor regression post-NAC. Altogether, 1,056 patients had undergone FLOT or DCF regimes, while 1,610 patients had received ECF or ECX. The pCR rates ranged from 3.3% to 54% for FLOT regimes, while pCR ranged between 0% and 31% for ECF/ECX protocols. Pooled random-effects meta-meta-analysis of proportions showed a statistically significant higher incidence of pCR in FLOT-based chemotherapy at 0.148 (95%CI: 0.080, 0.259) compared with non-FLOT-based chemotherapy at 0.074 (95%CI: 0.042, 0.129). However, pCR rates were significantly highest at 0.250 (95%CI: 0.202, 0.306) for CRT. The use of enhanced FLOT-based regimens have improved the pCR rates for chemotherapeutic regimes but still falls short of pathological outcomes from CRT. Further work can characterize clinical responses to neoadjuvant therapy and determine whether an organ-preservation strategy is feasible.