Esophageal Cancer: An Updated Review

Abstract and Introduction

Abstract

The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.

Introduction

The use of colonoscopy for colorectal cancer (CRC) prevention screening has been a public health success. The reported data suggest that since instituting widespread colonoscopy use, there has been an approximately 50% decline in CRC mortality.^[1] It is unfortunate that we have not been as successful with screening for other malignancies of the gastrointestinal tract, because many still present with advanced disease and thus have poor outcomes. Using the dictum that early detection defines cures, this review focuses on the state of esophageal cancer (EC) screening and prevention. Although less common than CRC, EC carries a much more moribund prognosis, with a 5-year survival rate of <5%.^[2] Compounding the issue, EC encompasses two distinct subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC). In this review we address the present trends in epidemiology, risk factors, screening, and preventive strategies for both subtypes. Although the data at present have failed to support population-based screening strategies for EC, we review some specific demographical and clinical conditions for which screening is appropriate.^[3]

Table 1. Risk factors for EC
ESCC	Risk of ESCC	EAC	Risk of EAC
Smoking	High	BE¹⁰	High
Caustic ingestion¹¹	High	GERD severe, symptomatic¹⁰	High
Tylosis (AD)^12–14	High	Family history EAC^10,14	Intermediate–high
Achalasia	High	Obesity^14,15	Intermediate–high (not adjusted for GERD/BE)
Fanconi anemia (AR)^{12–14,16,17}	High	Smoking	Low–intermediate
Smoking + alcohol¹⁴	High
Plummer-Vinson syndrome	Intermediate–high	Smoking + alcohol former	Intermediate
Scleroderma¹⁴	Intermediate–high
Alcohol¹⁴	Intermediate
Celiac disease	Low
Bloom syndrome (AR)¹⁸	Limited data
Howel-Evans syndrome (AD)^12,13	Limited data

High risk: OR/RR/HR >3; intermediate risk: OR/RR/HR 2–3; low but above-average risk: OR/RR/HR 1–2. AD, autosomal dominant; AR, autosomal recessive; BE, Barrett's esophagus; EAC, esophageal adenocarcinoma; EC, esophageal carcinoma; ESCC, esophageal squamous cell carcinoma; GERD, gastroesophageal reflux disease.

Table 2. Risk factors for and the progression of BE
Risk factors favoring BE screening⁴²	PIB score^43,44
Smoking	BE with LGD (11 points)
Family history of BE or EAC	Male sex (9 points)
Male sex	Smoking (5 points)
Obesity	BE without dysplasia (1 point/cm)
Central obesity	Yearly risk of progression based on points
GERD	2% above >20; 0.73% 11–20; 0.13% <10 points

High-risk group: smoking, family history of BE or EAC; moderate-risk group: GERD + central obesity; for each additional risk factor, BE risk increases by 1.2%. PIB scoring may be helpful when discussing surveillance and treatment options with patients diagnosed as having nondysplastic BE. BE, Barrett's esophagus; EAC, esophageal adenocarcinoma; GERD, gastroesophageal reflux disease; PIB, Progression in BE; LGD, low-grade dysplasia.