Downstaging depth score as a better surrogate endpoint than pCR, histological response and ypN0 for long-term outcomes in locally advanced gastric cancer patients after preoperative chemo-radiotherapy

Background: The prediction effect of preoperative chemo-radiotherapy(CRT) is not high and difficult to guide individualized treatment. We explored a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT. Methods: From April 2012 to April 2019, 95 patients enrolled in 4 prospective studies with locally advanced gastric cancer who received preoperative concurrent radio-chemotherapy were included. All patients were stage T3/4, N+. Local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were evaluated. The clinicopathological factors related to the long-term prognosis were analysed by uni- and multivariant analyses. The downstaging depth score (DDS), a novel method of evaluating the CRT response, was used to predict long-term outcomes. Results: The median follow-up period for survivors was 30 months. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve predicted by the DDS was 0.728, which was better than that of pathological complete response (pCR), histological response and ypN0 (AUC= 0.634, 0.640 and 0.643, respectively). The DDS cut-off value was 4. pCR and ypN0 were associated with OS (p = 0.026, 0.049). Surgery and the DDS were correlated with DMFS, DFS and OS (p = 0.001, 0.000, and 0.000 and 0.009, 0.013, and 0.032, respectively). The multivariate analysis showed that the DDS was an independent prognostic factor of DFS (p = 0.021). Conclusion: The DDS, a simple, short-term indicator, seems to be a better surrogate endpoint than pCR, histological response and ypN0 for DFS.