- Esophageal cancer is the 6th most common cancer worldwide, with an estimated 450,000 deaths per year.
- Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended.
- For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered.
- For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered.
- Multimodality therapy should be offered to patients with locally advanced esophageal carcinoma. (Strong Recommendation; EB-B-M).
Note: Although outside the scope of recommendations for locally advanced esophageal cancer, the Expert Panel recommends that for patients with clinical earlier stage esophageal cancer (T2, N0), surgery alone may be considered after discussion with a multidisciplinary team. Within this group, surgery alone may be more appropriate for patients with low risk cT2NO lesions (i.e. well-differentiated, less than 2 cm), and where there is a sufficient degree of confidence in the results of pretreatment staging.
- Preoperative chemoradiotherapy (CRT) or perioperative chemotherapy (CT) should be offered to patients with locally advanced esophageal adenocarcinoma. (Strong Recommendation; EB-B-M).
- For the subgroup of patients for whom surgery is not feasible, CRT without surgery is recommended.
- Preoperative CT should be considered for patients who are not candidates for radiation or postoperative chemotherapy.
- Postoperative complications may be more severe with CRT as compared to CT. Consider the potential for patient tolerance of the addition of RT based on tumor location and other factors.
- The addition of radiotherapy is expected to be more beneficial in the setting of less extensive surgery. Adequate quality and extent of surgery includes clear surgical margins and adequate nodal dissection within appropriate nodal fields, e.g. abdominal and thoracic, with a goal of obtaining at least 16 to 18, and preferably greater than 20 lymph nodes. Lymphadenectomy fields and extent of surgery will be affected by tumor location. Detailed recommendations for surgical approach are beyond the scope of this guideline.
Note: While outside the scope of the systematic review, the Expert Panel recognizes FLOT as the standard of care for perioperative chemotherapy in esophageal adenocarcinoma. The FLOT regimen includes 4 preoperative and 4 postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-hr infusion on day 1. Where the FLOT regimen is not available or feasible, the Expert Panel suggests cisplatin-fluorouracil (two 3-weekly cycles of cisplatin [80 mg/m2 intravenously on day 1] and fluorouracil [1 g/m2 per day intravenously on days 1–4]), or a similar platinum-based regimen.
- Preoperative CRT or CRT without surgery (definitive CRT) should be offered to patients with locally advanced esophageal squamous cell carcinoma. (Strong Recommendation; EB-B-M)
- Historical studies suggest that in patients who respond completely to CRT, the addition of surgery may offer minimal benefit. In patients with squamous cell carcinoma who appear to have a complete response to CRT, the option of surveillance and salvage surgery upon progression may be considered, where salvage esophagectomy is practiced. At this time, randomized controlled trials are exploring the question of surveillance and salvage surgery after CRT compared to planned surgery after CRT.
- In patients for whom radiation is not an option, preoperative CT (without radiation) may be considered.
- Definitive CRT is recommended for patients with tumors located in the cervical esophagus; surgery should be considered in the event of persistent or recurrent disease.
- While CRT and surgery are preferred, definitive CRT is an option for patients who cannot tolerate or choose not to undergo surgery.
- For patients with esophageal squamous cell carcinoma, the decision to undertake surgery should be considered in the context of shared decision making, considering age, comorbidities, patient preference, caregiver support, and other factors. (CB-H)
ASCO Recommendation Update – August 2021
- Following neoadjuvant CRT and surgery, nivolumab should be offered to patients with locally advanced esophageal carcinoma with Eastern Cooperative Oncology Group status 0-1 who did not experience a pathological complete response (i.e., with residual disease of at least ypT1 or ypN1 in resected specimens). (Strong Recommendation; EB-B-M).
- Data are not available to support any recommendation for nivolumab following treatment with perioperative chemotherapy.
- A post-hoc analysis showed an HR for disease-free survival of 0.62 (95% CI, 0.46 to 0.83, median DFS 29.4 vs. 10.2 months) in the subgroup of patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) of at least 5 (n=371) and 0.89 (95% CI, 0.65 to 1.22, median DFS 16.3 vs. 11.1 months) in the subgroup of patients with PD-L1 CPS of less than 5 (n=295). This exploratory analysis suggests that future studies may define biomarkers, such as PD-L1 CPS, and/or a subgroup that will benefit from adjuvant nivolumab.