gms | German Medical Science

Background: Gastroesophageal adenocarcinoma, i.e. adenocarcinoma of the esophagus, gastroesophageal junction and stomach, has a poor prognosis in advanced stages. Recent trials and meta-analyses have demonstrated that neoadjuvant chemotherapy and chemoradiotherapy prolong survival. It is unclear if patients who received neoadjuvant therapy benefit from postoperative continuation of chemotherapy. The decision for or against continuation could be supported by estimating postoperative survival. Therefore, by pooling individual patient data (IPD) from randomized controlled trials (RCTs), we aimed to identify predictors for postoperative survival in patients with gastroesophageal adenocarcinoma who underwent neoadjuvant chemotherapy and compare it to patients who had surgery alone.

Materials and methods: The study used IPD from RCTs comparing neoadjuvant chemo(radio)therapy with surgery alone for gastroesophageal adenocarcinoma. These data have already been used in a meta-analysis comparing the two treatment approaches. Inclusion criteria were: resectable gastroesophageal adenocarcinoma with no metastasis on staging; comparing neoadjuvant chemotherapy or chemoradiotherapy followed by surgery with surgery alone. All trials providing IPD on age, sex, performance status, pTN stage, resection status, overall and recurrence-free survival were included. Survival was calculated with the Kaplan-Meier method separately for patients who received neoadjuvant therapy (CTX group) and patients who underwent surgery alone (surgery group), in the entire study population and in subgroups stratified by supposed predictors. Survival was compared using the log rank test. Multivariable Cox regression models were used to identify independent predictors of survival.

Results: Five trials providing IPD from 553 patients fulfilled the inclusion criteria. All trials had neoadjuvant regimens consisting of chemotherapy without irradiation. On postoperative histology, patients in the CTX group had significantly less advanced T and N stages, and resection margins were significantly more often tumor-free. Kaplan-Meier curves for overall survival in the CTX and surgery arms are displayed for the entire study population and stratified by the supposed predictors (figure). There was a significant benefit in overall survival for CTX, which translates into a 15% difference in 5-year survival. (y)pT and (y)pN stage as well as resection status were strong predictors of postoperative survival both in the CTX and surgery group. Patients with R1 resection in the CTX group survived longer than those with R1 resection in the surgery group. Patients with stage pN0 in the surgery group had better prognosis than those with ypN0 in the CTX group. Patients with stage ypT3/4 in the CTX group had better prognosis than those with stage pT3/4 in the surgery group. Multivariable regression identified resection status and (y)pN stage as predictors of postoperative survival in both group. (y)pT stage predicted survival only in patients after surgery alone but not neoadjuvant therapy.

Conclusion: Neoadjuvant chemotherapy prolongs survival in gastroesophageal adenocarcinoma. After neoadjuvant therapy, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision for or against postoperative continuation of chemotherapy in patients who had received neoadjuvant treatment.

Figure 1 [Fig. 1]