Esophagogastric Junction Carcinoma: Introduction

Volume 23, Number 1

January 2013

Esophagogastric Junction Carcinoma: Introduction

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sophagogastric junction (EGJ) tumors have been the subject of much debate over the past several decades, both in regard to their diagnostic classification as well as their therapeutic management. This is due, in large part, to difficulties in determining whether an EGJ malignancy is a primary esophageal or gastric lesion, and thus, there is significant variability as to whether these tumors are treated according to esophageal or gastric regimens. However, with the sharp rise in incidence of EGJ adenocarcinomas over the past 30 years, it is gaining increasing importance as a public health problem. Whereas cases of distal gastric adenocarcinoma have steadily declined, the incidence of EGJ adenocarcinoma has increased 2.5-fold since the 1970s (Buas, this issue). In 2012, an estimated 38,780 patients will be diagnosed, with an estimated 25,610 deaths from gastric or esophageal cancers in the United States.1 As such, there is a mounting need to better define EGJ tumors as a disease entity and to identify more effective therapeutic approaches specifically for this challenging malignancy. The Siewert classification was originally developed to describe the position of tumors relative to the EGJ and to direct management of these tumors. In 2000, the classification was further refined: Siewert type I tumors are defined as having a tumor center located within 1-5 cm above the anatomic EGJ; Siewert type II tumors are within 1 cm above and 2 cm below the EGJ; and Siewert type III are tumors centered between 2 and 5 cm below the EGJ, infiltrating the EGJ from below.2 One strategy has been to treat proximal EGJ tumors (eg, Siewert I and II) with preoperative chemoradiotherapy as per esophageal cancer, and more distal tumors with the various regimens established for gastric cancer. However, this remains controversial. Yet, recent data indicate that the behavior and response to treatment for EGJ adenocarcinomas is similar to that of distal esophageal adenocarcinoma, and therefore, the clinical distinction between the 2 may not be of critical importance.3 Staging EGJ tumors has also been fraught with difficulties. Until recently, American Joint Cancer Committee (AJCC) staging of esophageal and gastric cancers was discordant, creating significant potential for confusion. In the revised AJCC staging system (7th edition) for esophagus cancer, all tumors with an epicenter in the lower thoracic esophagus, EGJ, or within the proximal 5 cm of the stomach that extend 1053-4296/13/$-see front matter © 2013 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.semradonc.2012.09.007

into the EGJ or esophagus (Siewert types I and II) are classified in the same category as esophageal cancers.4,5 The revised AJCC staging system speaks to the importance of having more standardized approaches to EGJ cancers and of the greater need for concordance between the various specialists who are treating these patients. Whether EGJ cancer patients have been treated on esophageal or gastric cancer protocols, these cancers require a multidisciplinary approach. In this issue of Seminars in Radiation Oncology, we have contributions from the leading experts in the field from various specialties, representing the multidisciplinary nature of the diagnosis and management of EGJ carcinoma. Drs. Buas and Vaughan describe the rising incidence in this cancer subtype over the past few decades and elaborate on the risk factors that may be contributing to this rise. They also describe the ongoing work exploring the potential role for chemopreventive agents. Dr. Wu and I discuss the role of positron emission tomography (PET) imaging, which has been a standard component of the workup of esophageal EGJ cancers over the past decade and is being evaluated as an imaging biomarker to help direct chemotherapeutic choices. Our thoracic surgery colleagues, Drs. Amenabar, Hoppo, and Jobe, review the controversies and challenges of surgery for EGJ tumors, which remains the mainstay for potentially curative therapy. They describe the lymphatic drainage patterns and surgical techniques, including the role of more extended lymphadenectomies as well as the use of transthoracic versus transhiatal approaches. Drs. Ku and Ilson provide an update on the chemotherapeutic regimens that have been evaluated for metastatic EGJ adenocarcinomas, providing an overview of the current literature on first- and secondline therapy for this disease. Drs. Hong, Wo, and Kwak present the latest information on the targeted agents that are in clinical trials or in the pipeline. They critically evaluate the potential for new targets in EGJ tumors and describe the challenges in developing therapies that can exploit these targets. Dr. Kleinberg discusses the landmark studies establishing the use of multimodality therapy, from the early studies of chemoradiation alone and, more recently, the use of trimodality therapy for EGJ tumors. However, with the use of radiotherapy for these tumors, there are challenges in terms of treatment planning and potential toxicity, particularly 1

K.A. Goodman

2 when radiotherapy is combined with other modalities such as chemotherapy and surgery. Drs. Pepek, Willet, and Czito examine the treatment planning issues associated with thoracic and abdominal radiotherapy for EGJ tumors. Target volume definitions and technical advances in radiotherapy delivery approaches are addressed. Finally, Drs. Monjazeb and Blackstock look at the potential toxicities associated with multimodality therapy and appraise the current literature, summarizing findings on toxicity associated with chemoradiation and surgical complications. It is clear from this issue that there is a growing focus on this disease arising from the EGJ, both from the concern about the rising incidence and because of the need to address the long-standing controversies about the definition and management. Also concerning are the persistently low cure rates for this disease, despite aggressive multimodality therapy. Ultimately, improvement in outcome may only come with the identification of risk factors and chemopreventive mechanisms to reduce the incidence of this disease, as well as the development of molecular and imaging biomarkers to help guide therapy in patients who develop EGJ carcinoma. In the future, I predict that an issue in Seminars in Radiation

Oncology on EGJ carcinoma will include articles elucidating the molecular pathways in the development of this cancer and describing biological rationales for its therapy. Karyn A. Goodman, MD Guest Editor

References 1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 62:10-29, 2012 2. Rüdiger Siewert J, Feith M, Werner M, et al: Adenocarcinoma of the esophagogastric junction: Results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg 232:353-361, 2000 3. Leers JM, DeMeester SR, Chan N, et al: Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus. J Thorac Cardiovasc Surg 138:594-602, 2009 4. Rice TW, Rusch VW, Ishwaran H, et al: Worldwide Esophageal Cancer Collaboration. Cancer of the esophagus and esophagogastric junction: Data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Staging Manuals. Cancer 116:3763-3773, 2010 5. Edge SB, Byrd DR, Compton CC, et al: AJCC Cancer Staging Manual (ed 7). New York, Springer, 2010