Does a Lymph Node-Based Model Predict Clinical Value for Adjuvant Therapy in Squamous Cell Carcinoma of the Esophagus Treated With Upfront Surgery?

Abstract

The management of esophageal cancers is different outside the Western world, where the majority of esophageal cancer histology is squamous cell carcinoma (SCC) and many high-volume centers still use an esophagectomyfirst approach. This differs from Western methodology, which is rooted in the landmark 2012 randomized ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial, which demonstrated a clear difference in median overall survival of 49.4 versus 24.0 months between neoadjuvant chemoradiotherapy plus surgery and surgery only, respectively. The safety and efficacy of the CROSS regimen led to its wide adoption in North America, with neoadjuvant chemoradiotherapy for all esophageal carcinomas and consideration of surgery as trimodality therapy for appropriate candidates. The response to neoadjuvant treatment appears to matter regardless of histology. Unlike the epidemiologic pattern in the remainder of the world, SCC comprised only 23% of all histology in the CROSS trial, but it was more responsive to upfront treatment than adenocarcinoma (AC), with a complete response rate of 49%. The complete response with neoadjuvant therapy certainly has prognostic merit. 3 Nevertheless, despite promising data for complete pathologic responders, 33% of these patients will experience recurrence, often with metastatic disease and a poor prognosis. To identify these patients early and treat them aggressively seems logical, but to date, no clear randomized data exist to support adjuvant therapy. Based on National Comprehensive Cancer Network (NCCN) guidelines, no clear treatment recommendations are made for ypT ? or ypN ? resected squamous cell carcinomas, and only limited data support delivery of adjuvant therapy in the adenocarcinoma group. Because the majority of histology and tumor biology differs outside the Western world, it is understandable that neoadjuvant therapy has not been widely adopted for treatment of squamous cell esophageal carcinoma. Supporting the findings of the CROSS trial, Yang et al. randomized a non-Western group of squamous cell carcinoma patients to neoadjuvant chemoradiotherapy followed by surgery compared with surgery alone for locally advanced esophageal cancers and demonstrated a significant prolonged disease survival of 100.1 versus 41.7 months, respectively. Despite an accruing body of data from these and other international trials, a surgery-first approach to esophageal squamous cell carcinoma still is most popular currently. Without a downstaging opportunity using chemoradiotherapy, the adjuvant management of pathologically positive lymph nodes, even after radical three-field lymphadenectomy, becomes extremely important for survival optimization. In the context of a surgery-first approach, we applaud Li et al. in their attempt to establish prognostic criteria to define patients most suitable for adjuvant therapy. The authors evaluated the utility of pN stage, lymph node ratio (LNR, calculated as the number of positive nodes/total number of nodes), and total number of resected lymph Editorial on ‘‘Predicting the Value of Adjuvant Therapy in Esophageal Squamous Cell Carcinoma by Combining the Total Number of Examined Lymph Nodes With the Positive Lymph Node Ratio’’ by Li, Yida et al. (ASO-2019-02-0317.R1).