Impact of pathological tumor response after CROSS neoadjuvant chemoradiotherapy followed by surgery on long-term outcome of esophageal cancer: a population-based study

Abstract

Background: With increasing interest in organ-preserving strategies for potentially curable esophageal cancer, real-world data is needed to understand the impact of pathological tumor response after neoadjuvant chemoradiotherapy (CRT) on patient outcome. The objective of this study is to assess the association between pathological tumor response following CROSS neoadjuvant CRT and long-term overall survival (OS) in a nationwide cohort. Material and methods: All patients diagnosed in the Netherlands with potentially curable esophageal cancer between 2009 and 2017, and treated with neoadjuvant CRT followed by esophagectomy were included. Through record linkage with the nationwide Dutch Pathology Registry (PALGA), pathological data were obtained. The primary outcome was pathological tumor response based on ypTNM, classified into pathological complete response (ypT0N0) and incomplete responders (ypT0Nþ, ypTþN0, and ypTþNþ). Multivariable logistic and Cox regression models were used to identify predictors of pathological complete response (pCR) and survival. Results: A total of 4946 patients were included. Overall, 24% achieved pCR, with 19% in adenocarcinoma and 42% in squamous cell carcinoma. Patients with pCR had a better estimated 5-year OS compared to incomplete responders (62% vs. 38%, p< .001). Of the patients with incomplete response, ypTþNþ patients (32% of total population) had the lowest estimated 5-year OS rate, followed by ypT0Nþ and ypTþ N0 (22%, 47%, and 49%, respectively, p< .001). Adenocarcinoma, well to moderate differentiation, cT3-4, cNþ, signet ring cell differentiation and lymph node yield (15) were associated with lower likelihood of pCR. Conclusion:In this population-based study, pathological tumor response based on the ypTNM-stage was associated with different prognostic subgroups. A quarter of patients achieved ypT0N0 with favorable long-term survival, while one-third had an ypTþNþ response with very poor survival. The association between pathological tumor response and long-term survival could help in more accurate assessments of individual prognosis and treatment decisions.

A population-based study in resected esophageal or gastroesophageal junction cancer aligned with CheckMate 577

“… 4 – 6 The addition of adjuvant treatment could particularly be interesting for patients with residual pathological disease after neoadjuvant chemoradiotherapy who have poorer outcomes compared with patients without residual pathological disease. 7 – 9 …”

Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance

“…Currently, pathological assessment according to ypTNM remains the gold standard for prognostic response evaluation and staging 3,4 . Pathologically complete response after nCRT is achieved in 23% of potentially curable oesophageal adenocarcinomas 5 and is associated with a favourable disease‐free survival 6–8 . The majority of patients, however, have pathologically incomplete response with residual tumour cells at the site of the primary tumour and/or in resected regional lymph nodes, which is associated with a less favourable outcome 8 …”

Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma

“…However, the treatment responses are highly variable, with only 19% of EACs achieving a complete histopathological response after CRT. 2 Incomplete response is a strong predictor of disease recurrence and reduced survival following surgical resection. 3 , 4 It is still not apparent which biological factors contribute to the variability in response, but accumulating evidence points toward a role for local anti-tumor immunity.…”