Esophageal Cancer
Background
What are the boundaries of the esophagus that divide it into cervical, upper thoracic, mid-thoracic, and lower thoracic regions?
The esophagus spans from the cricopharyngeus at the cricoid to the gastroesophageal (GE) junction. Relative to the incisors, the cervical esophagus spans from 15–18 cm, the upper thoracic from 18–24 cm, the mid thoracic from 24–32 cm, and the lower thoracic from 32–40 cm.
What is the incidence and mortality of esophageal cancer in the U.S.?
In 2009, 16,470 cases were diagnosed, with 14,530 estimated deaths. Median age is 69 yrs. (ACS 2009)
What is the racial and gender predilection of developing esophageal cancer?
The racial predilection depends on histology. Squamous cell carcinoma (SCC) is 3 times more common in blacks, whereas adenocarcinoma is more common in whites. Males are more commonly affected than females (nearly 3:1).
What are the risk factors of developing esophageal cancer?
Esophageal SCC risk factors: smoking/alcohol tylosis, Plummer-Vinson syndrome, caustic injury to the esophagus, Hx of H&N cancer, and achalasia. HPV infection has been associated in ~20% cases in high-incidence areas (China, Africa, Japan) but none in low-incidence areas (Europe, U.S.).
Esophageal adenocarcinoma risk factors: obesity/GERD, Barrett esophagus, lack of fruits/vegetables, low socioeconomic status
What are some protective factors for developing esophageal cancers?
Protective factors for developing esophageal cancer include fruits/vegetables and Helicobacter pylori infection (possible atrophic gastritis).
How do pts with esophageal cancer typically present?
Dysphagia and weight loss (>90%), odynophagia, pain, cough, dyspnea, and hoarseness
What is the pattern of spread of tumors of the esophagus?
Tumors of the esophagus spread locoregionally through the extensive submucosal lymphatic plexus or distantly through hematogenous routes.
What histologies predominate based on the tumor location within the esophagus?
The proximal three fourths of the esophagus (cervical to mid thoracic) are mostly SCCs (~40%), whereas adenocarcinoma generally is found in the distal esophagus (~60%).
What are some other more uncommon histologies seen for tumors of the esophagus?
Adenocytic, mucoepidermoid, small cell, and sarcomatous (leiomyosarcoma) carcinomas (all typically 1% of cases). Extremely rare types are lymphoma, Kaposi sarcoma, and melanoma.
What are the patterns of failure (locoregional vs. distant) relative to the histology and tumor location of esophageal cancers?
The patterns of recurrence from surgical series suggest that there is predominant LRF in cancers of the upper and middle esophagus (mostly squamous cell), whereas distant recurrence is more common in lesions in distal third of the esophagus (mostly adenocarcinomas). (Mariette C et al., Cancer 2003; Katayama A et al., J Am Coll Surg 2003)
What are the common sites of DM seen for esophageal cancers?
Lung, liver, and bone are the most common sites of distant Dz.
What % of pts with esophageal cancers present with localized Dz vs. distant Dz?
The extent of Dz at presentation depends on the location and size of the tumor. Dz at the middle and lower third of the esophagus tends to present with localized Dz (25%–50%), whereas upper thoracic Dz tends to be less localized Dz (10%–25%). Tumors >5 cm also tend to have greater metastatic rate (~75%) than tumors <5 cm.
What is the most important factor that determines nodal mets and DM?
DOI is the most important factor dictating nodal and distant spread. (Mariette C et al., Cancer 2003)
What is the extent of submucosal spread of Dz seen for esophageal cancers, and does it differ by histology?
Gao XS et al. reported the following for SCC: proximal and distal spread 10.5 +/− 13.5 mm and 10.6 +/− 8.5 mm, respectively, with 94% of pts having all tumor contained within a 30-mm margin. For adenocarcinoma, spread of Dz to 10.3 +/− 7.2 mm proximally and 18.3 +/− 16.3 mm distally, with a margin of 50 mm required to encompass all tumor in 94% of cases. (IJROBP 2007)
Workup/Staging
What components of the Hx are important in assessing a pt with dysphagia?
Appropriate parts of the Hx in assessing dysphagia Sx include onset, duration, solids vs. liquids, other Sx of retrosternal pain, bone pain, cough, hoarseness, Hx of smoking/alcohol, GERD, and Hx of prior H&N cancer.
What should be included in the workup of pts with suspected esophageal cancers?
Suspected esophageal cancer workup: H&P, labs (LFTs, alk phos, Cr), esophagogastroduodenoscopy with Bx. If cancer, then EUS + FNA for nodal sampling for T&N staging, CXR, bronchoscopy (for upper/mid thoracic lesions to r/o tracheoesophageal fistula), and PET/CT. Laparoscopic staging is done in some institutions, with reports of upstaging and sparing the morbidity of more aggressive Tx in 10%–15% of cases.
To what anatomic extent is esophageal cancer being defined?
Esophageal cancer is defined as 15 cm from the incisors to the GE junction and the proximal 5 cm of the stomach. Stomach tumors arising ≤5 cm from the GE junction or above is considered esophageal cancer.
What is new about the AJCC 7th edition (2009) of the TNM staging for esophageal cancer?
The new system distinguishes the number of nodal mets, subclassifies T4 Dz, expands the Tis definition, and removes the M1a-b designation.
Tis: high-grade dysplasia and CIS
T1a: involves lamina propria or muscularis mucosae
T1b: involves submucosa
T2: invades muscularis propria
T3: invades adventitia (Note: No serosal layer.)
T4a: pleural, pericardial, or diaphragm involvement
T4b: other organs (aorta, vertebral body, trachea)
Nx: regional nodes cannot be assessed
N0: no regional node mets
N1: 1–2 regional LN mets, including nodes previously labeled as M1a*
N2: 3–6 regional LN mets, including nodes previously labeled as M1a*
N3: ≥7 regional LN mets, including nodes previously labeled as M1a*
*M1a (differ by site): upper thoracic includes cervical LN mets; mid thoracic is not applicable; lower thoracic/GE junction includes celiac LN mets. (Note: M1a designation is no longer recognized in the 7th edition.)
M1: DM (retroperitoneal, para-aortic LN, lung, liver, bone, etc.)
What are the AJCC 7th edition (2009) stage groupings for esophageal cancer, and what new feature has been added?
Tumor grade (1-3) has been added to the TNM stage groupings, and separate stage groupings are given for SCC and adenocarcinoma.
Stage 0: TisN0M0, G1
Stage IA: T1N0M0, G1-2
Stage IB: T1N0M0, G3; T2N0M0, G1-2
Stage IIA: T2N0M0, G3
Stage IIB: T3N0 or T1-2N1, any G
Stage IIIA: T1-2N2M0, any G; T3N1M0, any G; T4aN0M0, any G
Stage IIIB: T3N2M0, any G
Stage IIIC: T4aN1-2M0, any G; T4b or N3, any G
Stage IV: TXNXM1
Why does SCC have a separate stage grouping from adenocarcinoma in the new staging system?
Tumor location is accounted for in the stage grouping for SCC, with lower regions having a better prognosis compared with upper and middle regions. The only changes compared to adenocarcinoma is in IA, IB, IIA, and IIB stage groupings:
Stage IA: T1N0M0G1, any location
Stage IB: T1N0M0G2-3 any location; T2-3N0M0G1, lower location
Stage IIA: T2-3N0M0G1, upper/middle location; T2-3N0M0G2-3, lower location
Stage IIB: T2-3N0M0G2-3, upper location/middle location; T1-2N1M0 any G, any location
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