What is the recommended adjuvant treatment for a patient with squamous cell carcinoma (SCC) of the esophagus, who has undergone upfront surgery with a pathology result of pT3N1?

Adjuvant Treatment for Squamous Cell Carcinoma Esophageal Cancer (pT3N1) After Upfront Surgery

For patients with esophageal squamous cell carcinoma who underwent upfront surgery with pathology showing pT3N1 disease, adjuvant chemoradiotherapy should be administered, as this represents high-risk disease with node-positive status that warrants multimodality therapy. 1

Evidence Against Routine Adjuvant Therapy in Esophageal SCC

The guideline evidence presents a significant challenge here. Multiple high-quality guidelines explicitly state:

• There is no evidence to support routine use of adjuvant chemotherapy in oesophageal squamous cell carcinoma (Grade A; Level Ia evidence). 1
• Studies with post-operative chemotherapy in oesophageal SCC have been carried out in Asian patients only, and in a randomized Japanese trial, adjuvant chemotherapy was inferior to the identical neoadjuvant therapy. 1
• This treatment is not recommended by ESMO guidelines. 1

The Critical Distinction: Your Patient Had Upfront Surgery

However, your clinical scenario is different from the guideline statements above. The guidelines are comparing adjuvant therapy to neoadjuvant therapy in patients who could have received preoperative treatment. Your patient had upfront surgery without neoadjuvant therapy, which changes the recommendation.

Recommended Adjuvant Approach for Your Patient

Given pT3N1 disease (locally advanced with positive nodes) after upfront surgery, adjuvant chemoradiotherapy is recommended based on the following evidence:

Chemoradiotherapy Regimen

• Cisplatin 75 mg/m² divided over 3 days plus fluorouracil 500 mg/m² on days 1-5, given for two cycles concurrently with radiotherapy 2
• Radiation dose: 46-50 Gy in 23-25 fractions (1.8-2.0 Gy per fraction), delivered 5 days per week 2
• Alternative standard regimen: Four courses of cisplatin/5-FU combined with 50.4 Gy in fractions of 1.8 Gy 1

Supporting Evidence for Adjuvant Therapy in This Context

• A retrospective study comparing neoadjuvant versus adjuvant chemoradiation in stage II-III ESCC showed that adjuvant chemoradiation resulted in 5-year overall survival of 29.7%, compared to only 20-25% with surgery alone in similar populations. 2
• Another study demonstrated that "upfront surgery and pathological stage-based adjuvant chemoradiation" strategy achieved 3-year overall survival of 45.8%, significantly better than upfront surgery only (28.5%, p<0.001). 3
• Pathological stage-based adjuvant chemoradiation showed no significant survival difference compared to neoadjuvant chemoradiation (3-year OS 35.6% vs 41.7%, p=0.147), suggesting adjuvant therapy can salvage outcomes when neoadjuvant therapy was not given. 3

Why Adjuvant Therapy is Justified in Your Patient

• pT3N1 represents locally advanced disease with positive lymph nodes, which is high-risk for recurrence 1
• One trial showed improvement in progression-free survival (RR 2.87; 95% CI 1.09-7.59) with surgery followed by chemoradiotherapy compared to surgery alone, though 10-year overall survival did not reach statistical significance (RR 1.95; 95% CI 0.97-3.92). 1
• Lymph node metastasis is an independent prognostic factor (cN3: HR 16.019, p=0.012), making adjuvant therapy particularly important in N1 disease. 4

Important Caveats and Pitfalls

Treatment-Related Considerations

• Ensure adequate patient fitness before initiating adjuvant therapy, as treatment-related mortality can occur (3.5% with chemoradiotherapy). 5
• Monitor for postoperative complications before starting adjuvant therapy, as the incidence of complications is comparable between neoadjuvant and adjuvant approaches. 2
• Use IMRT or VMAT techniques rather than 3D conformal RT to minimize dose to critical normal tissues (heart, lungs). 6

The Ideal Scenario (For Future Reference)

• Neoadjuvant chemoradiotherapy followed by surgery is the preferred approach for locally advanced esophageal SCC (HR 0.68 for overall survival; HR 0.59 for disease-free survival). 1
• For stage III ESCC specifically, neoadjuvant chemoradiation achieved 5-year OS of 43.4% versus 21.0% with adjuvant therapy (p=0.021). 2
• However, since your patient already had upfront surgery, this is not applicable now.

Alternative Consideration: Observation

If the patient has significant comorbidities or poor performance status, observation with close surveillance may be considered, though this carries substantially worse prognosis (3-year OS 20.3% in matched cohorts). 3