Significance of tumour regression in lymph node metastases of gastric and gastro‐oesophageal junction adenocarcinomas

Abstract

The presence of lymph node (LN) metastases is one of the most important negative prognostic factors in upper gastrointestinal carcinomas. Tumour regression similar to that in primary tumours can be observed in LN metastases after neoadjuvant therapy. We evaluated the prognostic impact of histological regression in LNs in 480 adenocarcinomas of the stomach and gastro-oesophageal junction after neoadjuvant chemotherapy. Regressive changes in LNs (nodular and/or hyaline fibrosis, sheets of foamy histiocytes or acellular mucin) were assessed by histology. In total, regressive changes were observed in 128 of 480 patients. LNs were categorised according to the absence or presence of both residual tumour and regressive changes (LN−/+ and Reg−/+). 139 cases were LN−/Reg−, 28 cases without viable LN metastases revealed regressive changes (LN−/Reg+), 100 of 313 cases with LN metastases showed regressive changes (LN+/Reg+), and 213 of 313 metastatic LN had no signs of regression (LN+/Reg−). Overall, LN/Reg categorisation correlated with overall survival with the best prognosis for LN−/Reg− and the worst prognosis for LN+/Reg− (p < 0.001). LN−/Reg+ cases had a nearly significant better outcome than LN+/Reg+ (p = 0.054) and the latter had a significantly better prognosis than LN+/Reg− (p = 0.01). The LN/Reg categorisation was also an independent prognostic factor in multivariate analysis (HR = 1.23; 95% CI 1.1-1.38; p < 0.001). We conclude that the presence of regressive changes after neoadjuvant treatment in LNs and LN metastases of gastric and gastrooesophageal junction cancers is a relevant prognostic factor.

Tumor Regression in Lymph Node Metastases of Esophageal Adenocarcinomas after Neoadjuvant Therapy

“…We therefore decided to apply this system on the esophageal adenocarcinoma cohort, also allowing a direct comparison to the cohort of gastric carcinomas reported previously. The frequency of regressive changes of about 30% in LN metastases of a patient in our study is comparable to other studies, both for esophageal and gastric cancer [13,23,29,36]. One study by Zhu et al [37], however, reported a probability of occurrence of about 64%, which is as twice as much compared to other studies.…”

“…Even in patients who have not received chemoradiotherapy, fibrosis can occur in the sense of a body's own defensive reaction to tumor cells. However, it has been demonstrated before that the interobserver agreement for the determination of regressive changes in LNM is within substantial levels [13,29].…”

“…In upper gastrointestinal cancers LN staging has a very high prognostic value [14]. For tumors treated with multimodal therapy, previous studies postulated that, not only the ypN status, but also the additional reporting and categorization of lymph node metastasis regression, may have important prognostic value [13,23,[29][30][31][32][33][34].…”

“…Bollschweiler et al [35] introduced a classification with three grades: low risk (no LN metastasis and fewer than three LNs with central fibrosis), medium risk (no LN metastasis and central fibrosis in three or more LNs, or LN metastasis with a LN ratio of less than 0.05) and high risk (all other cases). A previous study of our group on gastric cancer [29] proposed a dichotomous classification, which focused only on the assessment of whether regression was present in any of the investigated lymph nodes. This system had been proposed by an expert panel for the application in gastric cancer [22].…”

Lymph Node Involvement in Advanced Gastric Cancer in the Era of Multimodal Treatment—Oncological and Surgical Perspective

“…Unnecessary reporting of nodal regression grade due to the higher prognostic value of LN's residual tumour assessment in predicting the prognosis after NAC was highlighted in a study from the East [108]. Despite usage of similar classification of regressive changes, this result stays in contradiction with European findings [110]. Both, nodal response and the quality of that response correlates with long-term survival.…”