Esophageal Cancer: New Insights into a Heterogenous Disease

Abstract

Background: Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols. Summary: With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved. Several trials confirmed a survival benefit for perioperative chemotherapy or neoadjuvant chemoradiation, respectively, for patients with resectable locally advanced adenocarcinomas. However, the question of whether perioperative chemotherapy or neoadjuvant chemoradiation is more effective for the long-term survival in this population has yet to be fully elucidated. In SCCs, neoadjuvant chemoradiation followed by surgery or definitive chemoradiation in case of functional inoperability represent the preferred treatment options. Compared to neoadjuvant protocols, adjuvant chemotherapy or chemoradiation have only minor effects and are associated with enhanced toxicities. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming to modulate immune check-points and dual inhibition of HER2. In this “to-the-point” article, we review the current standard and summarize the most recent and encouraging therapeutic advances in esophageal cancer. Multimodal treatment approaches for esophageal cancer should be discussed in a multidisciplinary team based on histology, tumor localization, and patient performance status. Neoadjuvant chemoradiation is beneficial for patients with locally advanced SCC and adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ), with perioperative chemotherapy representing a valid alternative for GEJ adenocarcinomas. Combination therapies are indicated for metastatic adenocarcinomas, while the benefit of palliative chemotherapy in SCC remains controversial. Trastuzumab is indicated in HER2+ metastatic adenocarcinomas.

Allelic Imbalance Analysis in Liquid Biopsy to Monitor Locally Advanced Esophageal Cancer Patients During Treatment

“…Esophageal cancer (EC) is a highly aggressive tumor, and the majority of patients die of recurrent disease within 2 years from diagnosis; this happens even after a putative radical esophagectomy ( 1 , 2 ). EC presents two main histotypes, which occur in distinct esophageal districts: adenocarcinoma (EADC) and squamous cell carcinoma (ESCC).…”

Long term follow-up of a large patient population with stage 2 and 3 esophageal cancer

“…Previous studies suggest that chemoradiation may lead to similar or greater outcomes than surgery alone, but results remain controversial [6]. trimodality approach has been shown, with the 2006 CALGB 9781 trial of 56 patients demonstrating an improvement of more than 50% in overall survival rates when compared with surgery alone [9]. Similarly, the CROSS study published in 2012 demonstrated signifi cantly increased survival with neoadjuvant chemoradiation compared with surgery alone (49.4 months vs. 24 months).…”

PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress

“…Esophageal cancer (EC) is one of the most common malignant tumors in the gastrointestinal tract . According to the WHO histological classification, EC mainly comprises squamous cell carcinoma (SCC) and esophageal adenocarcinoma, of which the proportion of SCCs is as high as 90% . In China, it is estimated that the average annual death total due to EC is ~150 thousand people, which accounts for 21.8% of all cancer mortalities .…”

“…1,2 According to the WHO histological classification, EC mainly comprises squamous cell carcinoma (SCC) and esophageal adenocarcinoma, of which the proportion of SCCs is as high as 90%. 3,4 In China, it is estimated that the average annual death total due to EC is~150 thousand people, which accounts for 21.8% of all cancer mortalities. 5 Among the leading causes of death, EC ranks fourth, with an average annual incidence of 17/1 000 000.…”