Pocket Oncology (Pocket Notebook Series), 1st Ed.

ESOPHAGEAL CANCER

Juliana Eng and David H. Ilson

Epidemiology

• In US, 17990 new cases esophageal CA estimated for 2013 (CA Cancer J Clin 2013;63:11–30); Worldwide 8th most common CA

• Squamous cell carcinoma most common in endemic regions of the world (South Africa, China, Iran, Russia); adenoca more common in many Western European countries & North America

Risk Factors

• Squamous: Tobacco & EtOH abuse, lye ingestion, achalasia, esophageal webs (Plummer–Vinson syn), small subset a/w HPV in some endemic regions; also ↑ risk of 2° aerodigestive tumors most likely 2/2 tobacco exposure

• Adenoca: Tobacco, obesity/↑ BMI, 60% cases w/evidence of Barrett esophagus: Squamous epithelium replaced w/intestinal columnar epithelium; found in 10–20% endoscopies evaluating GERD; w/surveillance endoscopy, 0.1–0.2%/y risk of developing CA

• Age, male gender, long-standing GERD, hiatal hernia size, length of Barrett esophagus is a/w higher grades of dysplasia → 10%/y risk of developing CA (Cancer 2007;109:668–674)

Genetics

• Tylosis palmaris et plantaris (focal nonepidermolytic palmoplantar keratoderma): Region of allelic deletion chromosome 17p, autosomal dominant, hyperkeratosis of palms & soles, esophageal papillomas, abnl maturation of squamous cells & inflamm w/in esophagus

• 4–7% pts w/Barrett may have a germline Mt in MSR1

Pathology/Etiology

• Squamous: Preceded by squamous dysplasia; 60% in middle third of esophagus, 30% distal third, & 10% proximal third

• Adenoca: Preceded by Barrett esophagus or incomplete intestinal metaplasia; low-grade → high-grade dysplasia → adenoca; usu. distal third of esophagus

• Others: Small cell (1%), SCCw/sarcomatous features, adenoid cystic, & mucoepidermoid CA

Siewert Classification for GE Junctions

• Type 1: Center of lesion 1–5 cm prox to GE jxn; Type 2: 1 cm prox to & 2 cm distal to GE jxn

• Type 3: 2–5 cm distal to GE jxn (Br J Surg 1998;85:1457–1459)

**All are treated as Esophageal CA(AJCC 2010 7th ed.)

Clinical Manifestations

• Sx: Most commonly progressive dysphagia → solids then liquids → cachexia & substantial wt loss; odynophagia, GI bleed

Figure 15-1

Screening and Prevention

• In North America & Western Europe, no screening programs for early detection; at dx ∼50% pts have locally adv CA

Staging and Workup

• PET/CT has a significantly higher accuracy in preop, occult M1 disease diagnosed in additional ∼10–15% pts, consider esp if CT w/LN; also helps determine response to preop chemo

• EUS for assessing depth of tumor invasion & regional LN, limited depth & visualization of transducer, suboptimal for distant LN

• Laparoscopy w/peritoneal washings considered for clinical T3 or N+ tumors, considered M1 if positive

• T = depth of tumor invasion [T1 lamina propria, muscularis mucosae, or submucosa; T2 muscularis propria; T3 adventitia; T4 resectable invading pleura, pericardium, or diaphragm(a) or unresectable invading other adj structures, such as aorta, vertebral body, trachea etc.(b)]

• N = # pos LN in regional LN groups (N1 1–2 LN; N2 3–6 LN; N3a 7 or more); Nodes in nonregional areas (hepatoduodenal, portal, paraaortic etc.) = distant mets (M1)

• Adenoca: Stage I: T1N0, T2N0 mod.–well differentiated, Stage II: T2N0 poorly differentiated, T3N0, T1–2N1, Stage III: T4N0, T3–4aN1, T1–4N2–3, Stage IV: M1 disease

• Squamous: Stage I: T1N0, T2–3N0 only if well differentiated + lower**, Stage II: T2–3N0, T1–2N1, Stage III: T4aN0, T3–4N1, T1–4N2–3, Stage IV: M1 disease (AJCC TNM staging 7th edition 2010)

  **Location defined by position of upper (proximal) edge of tumor

Early Disease (Stage I)

• Esophagectomy; consider endoscopic mucosal resection for Tis or T1a

• Most commonly used surgical techniques: (1) Transhiatal esophagectomy (for lower esophagus) & (2) Ivor Lewis resection, a transthoracic approach that uses a combo thoracotomy + laparotomy

• Goal of R0 resection (See Gastric Cancer Chapter)

Locoregional Disease (Stage II–III)

• Squamous: Definitive chemoradiation (fluoropyrimidine- or taxane-based regimens), surgery reserved for bx proven residual disease only; chemoradiation alone vs. chemoradiation + surgery (for responders only) → no difference in median OS despite improved local control (J Clin Oncol 2007;25:1160–1168)

• Adenoca: Preoperative chemotherapy ± radiotherapy → esophagectomy should be considered for all medically fit pts w/resectable esophageal adenoca (>5 cm from cricopharyngeus) bc compared to squamous, adenoca w/lower rate of pCR after chemoradiation, 49% vs. 23% (CROSS NEJM 2012;366:2074–2084)

• Bulky, multi-station LAN considered unresectable

• 5-y survival rate rarely exceeds 40%

• Neoadj tx improves outcomes (see below)

• T4b (unresectable) or cervical/cervicothoracic esophageal CA <5 cm from cricopharyngeus: Definitive chemoradiation

Neoadjuvant Therapy for Locoregional Disease

• Periop ECF: 13% ↑ 5-y OS rate, 36% vs. 23%, 26% pts had esophageal & GEJ CA, only 55% pts received postop Rx (MAGIC NEJM 2006;355:11–20)

• Preop Carbo/Taxol w/RT (41.4 Gy): 13% ↑ 5-y OS rate, 47% vs. 34%, median survival 49.4 vs. 24 mos, ↑ R0 resection rates of 92% vs. 69% (CROSS NEJM 2012;366:2074–2084)

Advanced Stage (IV) Treatment

• Treated as adv stage gastric CA, see Gastric Cancer Chap

• 2nd-line chemo: Fluoropyrimidines, platinums, taxanes, irinotecan, mitomycin-C, anthracyclines, MTX, vinorelbine, & GEM (Oncology 2007;21:579–586)

Targeted Therapy

• EGFR overexpressed 50–80%, TKIs & EGFR blocking ab inactive

• See Gastric Cancer Chap for other Targeted Therapies including Trastuzumab, Ramucirumab, & Rilotumumab for GEJ