BACKGROUND: The standard approach for the treatment of patients with locally advanced adenocarcinomas of the gastroesophageal junction (AGEJ) includes perioperative chemotherapy (CMT) or chemoradiation therapy (CRT). Although multiple RCTs have shown that a multimodal approach is superior to surgery alone, the optimal strategy regimen is unknown. Thus, this study aimed to evaluate the pathological and survival outcomes between AGEJ patients treated with preoperative CMT and CRT. METHODS: We included all AGEJ stage as cT2cN+ and cT3/4cN0/+ which were treated with CMT or CRT followed by curative-intent esophagectomy or total gastrectomy. CMT included fluorouracil, platinum, and taxane-based regimens. Pathologic tumor response was evaluated based on tumor regression grade (Ryan/CAP-TRG), where the pathological complete response (pCR) was defined as TRG0 and the absence or little response as TRG3. RESULTS: A total of 116 patients were included: 63 (54.3%) received CMT and 53 (45.7%) CRT. Esophagectomy was performed in 65.5% of patients and gastrectomy in 34.5%. Proximal tumors (Siewert I/II) (p=0.003) and esophagectomy (p<0.001) were more frequent in the CRT group. Regarding pathological characteristics, patients who underwent CRT had a lower rate of lymph node metastasis (p=0.059) and smaller tumor size (p<0.001). Lower angiolymphatic invasion (p=0.123) and ypT status (p=0.067) were also observed in CRT group, although not significant. pCR rate was higher in CRT group (13.2% vs 4.8%, p=0.004). Also, pathological complete lymph node response (pCR-LN) was significantly higher in the CRT group (30% vs 10.3%, p=0.013). Major postoperative complications (POC) were more common in the CRT group (p=0.025), and 30-day mortality was 4.8% and 13.2% in CMT and CRT groups, respectively (p=0.182). In survival analyses, the median disease-free survival (DFS) was 14 and 6.2 months for CMT and CRT group, respectively (p=0.064). Overall survival (OS) was better in CMT than CRT patients (31.8 vs 22.9 months, p=0.035). pCR was associated with better DFS and OS (p=0.051 and p=0.041, respectively). Regarding ypN status, patients with ypN0 had better DFS and OS compared to ypN+ (DFS: 28.7 vs 9.1 months, p=0.002; OS: not reached vs 20.2 months, p=0.002). In multivariate analysis, ASA III/IV, comorbidities, and ypN+ were independent factors associated with worse DFS. For OS, ASA, ypN+ and CRT were related with worse OS. For both DFS and OS, reaching ypN0 was the factor with better HR for improving survival. CONCLUSIONS: Preoperative CRT was associated with a higher pCR rate in the primary tumor, higher pCR-LN and less lymph node metastasis, but not with improved survival in AGEJ patients. Achieving an ypN0 status was the most important independent factor associated with survival. Also, the addition of CRT appears to be associated with an increased risk of POC and death.

Evandro Mello

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