Background: Perioperative chemotherapy (CMT) or chemoradiotherapy (CRT) associated with surgery is the standard approach for the treatment of resected gastroesophageal junction adenocarcinoma (AGEJ). However, the role of pathologically defined regression changes within the primary tumour (PT) and lymph nodes (LN) following CMT/CRT and the impact on survival remain unclear. This study aimed to evaluate regression changes in PT and LNs of AGEJ patients who received CMT/CRT, and its association with prognosis. Methods: We retrospectively reviewed AGEJ patients treated with perioperative CMT/CRT who underwent curative-intent esophagectomy or total gastrectomy. Pathologic tumor response in PT was evaluated based on tumor regression grade (Ryan/CAP-TRG). Regression within LNs was scored as present/absent (r+/-) according to the presence of fibrosis. Results: Among the 116 AGEJ, 28 (24.1%) had TRG0/1 and 88 (75.9%) TRG2/3. Ten (8.6%) patients had pathological complete response (pCR). Regarding the PT, smaller tumor size (p=0.001), less angiolymphatic and perineural invasion (p<0.001), ypN0 (p<0.001), and less advanced ypT and ypTNM (p<0.001) were associated with TRG0/1. Esophagectomy was performed more frequently in TRG0/1 than TRG2/3 cases (p=0.095); and the majority of TRG0/1 cases received CRT, while in the TRG2/3 group CMT was more frequent (p=0.036). Concerning LN regression, of the 108 cases evaluated (8 unavailable), 69 (63.9%) had signs of regression in the LNs: 21 ypN0r+ and 48 ypN+r+. The remaining 39 (36.1%) patients had no regressive changes in LNs: 23 ypN0r- and 16ypN+r- Accordingly, 23 (21.3%) AGEJ were classified as True-LN0; 21 (19.4%) as pCR-LN0; and 64 (59.3%) as non/incomplete LN regression (non/incLNR). pCR-N0 cases had less angiolymphatic invasion (p<0.001), smaller tumor (p=0.020), less advanced ypT and ypTNM (p<0.001) than True-N0 and non/incLNR groups. CRT (p=0.036) and TRG0/1 were more frequently in the pCR-LN0 (p<0.001). Also, pCR rate in PT was also higher in the pCR-LN0 group, even compared to the True-LN0 (13% vs 33.3%, p<0.001). Disease-free (DFS) and overall survival (OS) were slightly better in TRG0/1 compared to TRG2/3 (DFS: 19.8 vs 10.8 months, p=0.065; OS: 42.2 vs 23.4 months, p=0.085). Non/incLNR had worse DFS than pCR-LN0 (9.0 vs 26.9 months, p=0.046) and True-LN0 cases (p=0.003). Similar, OS was poorer for Non/incLNR compared to pCR-LN0 (20.2 vs 42.2 months, p=0.049) and True-LN0 (p=0.003). Also, there was no difference in DFS and OS between True-LN0 and pCR-LN0 (p=0.319 and p=0.315; respectively). Conclusion: pCR in LNs was associated with downstaging and PT regression, and ypN status with regression changes was the main factor associated with survival, not the TRG. AGEJ with pCR in LNs had similar survival than True-LN0. Also, the addition of CRT appears to be associated with an increased pCR in both LN and PT.
