Optimal Therapeutic Strategies for Resectable Oesophageal or Oesophagogastric Junction Cancer

Abstract

Oesophageal cancer is the eighth most common cancer diagnosed worldwide, with almost half a million new cases diagnosed each year. Despite improvements in surgical and radiotherapy techniques and refinements of chemotherapeutic regimens, long-term survival, even from localized oesophageal cancer, remains poor. Surgical resection alone remains the standard approach for very early stage disease (stage I), but whilst surgery remains fundamental to the treatment of stage II-III resectable adenocarcinoma, multimodality therapy with chemotherapy or chemoradiation (CRT) is internationally accepted as the standard of care. Data from two large, randomized phase III trials support the use of perioperative combination chemotherapy in lower oesophageal and oesophagogastric junction adenocarcinomas, but the contribution of the adjuvant therapy is uncertain. There are conflicting data from randomized studies of a purely neoadjuvant approach; however, recent meta-analyses have demonstrated that chemotherapy or CRT given prior to radical surgery improves survival in patients with adenocarcinoma of the oesophagus. Neoadjuvant CRT but not chemotherapy alone is also beneficial for patients with squamous cell carcinoma. Definitive CRT has emerged as a useful option for the treatment of resectable squamous cell carcinoma of the oesophagus, avoiding potential surgical morbidity and mortality for most patients, with salvage surgery reserved for those with persistent disease. In this review, we focus on the pharmacotherapy of resectable oesophageal and oesophagogastric junction cancers and how clinical trials and meta-analyses inform current clinical practice.

Factors influencing the risk of recurrence in patients with esophageal carcinoma treated with surgery: A single institution analysis consisting of 1002 cases

“…Given the recognized risk of local recurrence, even in patients with early-stage disease, we advise a re-analysis of post-operative radiotherapy and chemotherapy. The role of adjuvant therapy of ESCC has been addressed in a number of clinical trials; however, until presently, whether post-operative radiotherapy and/or chemotherapy affect the therapeutic outcomes has remained controversial (15)(16)(17)(18)(19)(20). Zhang et al (21) conducted a meta-analysis comprising a total of 1000 patients with esophageal cancer (ESCC and adenocarcinoma) in 2008.…”

Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis

“…Development of better preventive and diagnostic approaches as well as more effective treatment modalities requires an in-depth understanding of molecular mechanisms implicated in the complex process of esophageal carcinogenesis. Despite considerable diagnostic and therapeutic advances in the management of ESCC in recent years there still remains an urgent need for identification of novel molecular markers to provide the clinician with useful information concerning patient prognosis and possible therapeutic options [8-16]. In search of molecular markers our laboratory analyzed global gene expression profiles of ESCCs, using commercially available 19.1 k cDNA microarrays.…”

Prognostic impact of postoperative radiation in patients undergoing radical esophagectomy for pathologic lymph node positive esophageal cancer

“…Preoperative radiotherapy and chemotherapy are being used more often, and neoadjuvant chemoradiotherapy is currently the standard of care in many western countries [2-8]. Whether or not postoperative radiotherapy (PORT) and/or postoperative chemotherapy (POCT) affects treatment outcomes, however, remains controversial [9-12]. …”