What are the management options for a patient presenting with a distal esophageal mass, likely esophageal cancer?

Management of Distal Esophageal Mass

For a patient with a distal esophageal mass likely representing esophageal cancer, immediate endoscopic biopsy for histological confirmation is mandatory, followed by CT chest/abdomen as the first staging study to detect metastatic disease, then endoscopic ultrasound (EUS) if no metastases are found, with treatment determined by stage: early mucosal disease (T1a) can be treated with endoscopic resection, locally advanced resectable disease (T2-T4a, N0-3, M0) requires neoadjuvant chemoradiotherapy followed by transthoracic esophagectomy, and metastatic disease warrants palliative chemotherapy or endoscopic interventions for dysphagia. 1

Diagnostic Workup Algorithm

Initial Confirmation

• Obtain 6-8 endoscopic biopsies from the mass for histological diagnosis and molecular analysis, as this is the foundation for all subsequent management decisions 1
• Classify histology as adenocarcinoma versus squamous cell carcinoma, using immunohistochemistry if poorly differentiated, since treatment approaches differ significantly 1
• For adenocarcinoma patients who will receive immunotherapy, perform PD-L1 testing using either tumor proportion score (TPS ≥1%) or combined positive score (CPS) methods 1

Staging Sequence

Step 1: CT scan of chest and abdomen with contrast is the mandatory first staging study to identify distant metastases or clearly unresectable disease, which would fundamentally alter the treatment approach 1

Step 2: If CT shows no metastases, proceed to endoscopic ultrasound (EUS) with fine-needle aspiration of suspicious regional lymph nodes to assess T-stage (depth of invasion) and N-stage (nodal involvement) 1

Step 3: Add PET-CT scan if all previous studies show no metastatic disease, as it detects occult distant metastases in approximately 15% of cases that would change management from curative to palliative intent 1, 2

Step 4: For adenocarcinomas of the esophagogastric junction infiltrating the cardia, consider laparoscopy to rule out peritoneal metastases, which are found in 15% of patients and missed by CT/ultrasound in 85% of cases 1

Additional Assessments

• Perform bronchoscopy for mid-to-upper esophageal tumors to exclude tracheo-bronchial extension 1
• Assess nutritional status, performance status, and cardiopulmonary function (pulmonary function tests, ECG, exercise testing) to determine surgical candidacy 1

Treatment by Stage

Early Stage Disease (T1a N0 M0 - Mucosal)

Endoscopic resection is the treatment of choice for cancer confined to the mucosa, as the risk of lymph node metastasis is very low (<5%) 1

• Endoscopic submucosal dissection (ESD) is superior to endoscopic mucosal resection (EMR), achieving higher complete resection rates and lower local recurrence 1
• For squamous cell carcinoma, even deep intramucosal (m3) cancers require additional treatment if other risk factors are present, as lymph node metastasis risk is higher than adenocarcinoma 1
• Proceed to esophagectomy if deep resection margins are involved or significant risk factors for lymph node metastases exist (lymphovascular invasion, poor differentiation, submucosal invasion) 1

Locally Advanced Resectable Disease (T2-T4a, Any N, M0)

Neoadjuvant chemoradiotherapy followed by transthoracic esophagectomy is the standard of care for both adenocarcinoma and squamous cell carcinoma 1, 3, 4

Neoadjuvant Chemoradiotherapy Protocol

• Preferred regimen: Weekly carboplatin plus paclitaxel with concurrent radiation therapy to 41.4 Gy in 23 fractions over 5 weeks (CROSS protocol) 1, 3, 4
• Alternative: Cisplatin plus 5-fluorouracil with 50 Gy in 25 fractions over 5 weeks 1
• This approach achieves complete pathologic response in approximately 50% of squamous cell carcinoma patients and improves survival with hazard ratio of 0.34 for SCC versus 0.82 for adenocarcinoma 1, 4

Restaging After Neoadjuvant Therapy

Perform restaging 5-6 weeks after completion of chemoradiotherapy with: 1, 3

• Repeat CT chest/abdomen or PET-CT
• Upper endoscopy with biopsy (optional but recommended)
• EUS with fine-needle aspiration of suspicious nodes

Critical caveat: Even with apparent complete clinical response, 10% of patients have residual disease on pathology, so surgery should still be performed in operable candidates unless distant metastases develop or the patient becomes medically unfit 3, 4

Surgical Approach

Transthoracic esophagectomy with en bloc two-field lymphadenectomy is the procedure of choice: 1, 4

• For distal esophageal tumors: Ivor Lewis procedure (right thoracotomy and laparotomy with intrathoracic anastomosis)
• Resect minimum 15 lymph nodes for adequate staging 3
• Minimally invasive esophagectomy (including robotic techniques) achieves lower postoperative morbidity, quicker recovery, and better quality of life up to 1 year compared to open surgery, with non-inferior oncological outcomes 1
• R0 resection rates should exceed 30%, with hospital mortality <10% (ideally <5%) 1, 4

Caveat for T2 N0 Tumors

There is controversy regarding neoadjuvant therapy for clinical T2 N0 tumors, as randomized trials included few patients from this population 1. However, given the 20-30% risk of occult nodal disease and poor outcomes with surgery alone, neoadjuvant chemoradiotherapy is reasonable for most T2 tumors, with surgery alone reserved only for highly selected cases with favorable features 1

Alternative Strategy: Definitive Chemoradiotherapy with Selective Surgery

For squamous cell carcinoma only, definitive chemoradiotherapy with surveillance and salvage esophagectomy for local progression is an acceptable alternative to planned surgery, even in upfront resectable cases 1, 4

• Use the same chemoradiotherapy regimens but with curative radiation doses up to 60 Gy in 1.8-2.0 Gy fractions 1
• This approach is particularly appropriate for patients who refuse surgery, have significant comorbidities, or achieve complete clinical response after chemoradiotherapy 1, 4
• Do not use this strategy for adenocarcinoma, as surgery remains superior 1

Unresectable or Metastatic Disease (T4b or M1)

Palliative systemic chemotherapy is the primary treatment for metastatic disease: 1

• Fluoropyrimidine-based or taxane-based regimens
• For squamous cell carcinoma with PD-L1 positivity (TPS ≥1% or CPS ≥10), add immune checkpoint inhibitors (nivolumab or pembrolizumab) to chemotherapy as first-line treatment 1

Endoscopic palliation for dysphagia: 1

• Expandable metal stents (coated to prevent tumor ingrowth) are the preferred method for long-term palliation of tumors >2cm from the cricopharyngeal muscle
• Alternative ablative therapies: photodynamic therapy, laser therapy, or alcohol injection have similar efficacy but stents provide more durable relief
• Esophageal dilation provides only short-term relief

Nutritional support with enteral feeding (feeding tube) should be considered before chemotherapy or radiation therapy 1

Postoperative Management (For Patients Who Did NOT Receive Preoperative Therapy)

This scenario is uncommon but may occur if surgery was performed without proper staging:

• No further treatment for Tis or T1 N0 with R0 resection 1
• Postoperative fluoropyrimidine-based chemoradiotherapy for T3-T4a tumors or node-positive T1-T2 tumors with R0 resection 1
• For T2 N0 tumors, postoperative chemoradiotherapy is category 2B (only for high-risk features: poor differentiation, lymphovascular invasion, neural invasion, age <50 years) 1
• Fluoropyrimidine-based chemoradiotherapy for R1 (microscopic residual) or R2 (macroscopic residual) resections 1

Postoperative Management (For Patients Who Received Preoperative Therapy)

• Complete the perioperative chemotherapy (same regimen used preoperatively) for all patients with R0 resection, regardless of nodal status 1
• Observation is an alternative option 1

Common Pitfalls to Avoid

• Do not use preoperative radiotherapy alone without chemotherapy, as meta-analyses show insufficient survival benefit 1
• Do not assume complete clinical response equals complete pathologic response - always proceed with planned surgery unless contraindicated, as 10% have residual disease 3, 4
• Do not perform transhiatal esophagectomy for distal esophageal tumors in fit patients, as transthoracic approach provides superior lymph node dissection and oncological outcomes 1, 4
• Do not delay nutritional assessment and support - esophageal cancer patients are often malnourished at presentation, which increases surgical morbidity and impairs tolerance of chemoradiotherapy 1
• Do not forget to assess for synchronous primary tumors - perform head and neck examination for squamous cell carcinoma patients, as second primaries occur in the oropharynx in 5-10% of cases 1