Esophageal Cancer: Current Diagnosis and Management
Journal of Clinical Outcomes Management. 2014 August;21(8)
References
Locally Advanced Disease
Neoadjuvant Therapy
For patients with locally advanced cancer (ie, patients without distant metastases who have extension of the primary tumor into the deeper layers of the esophageal wall, including the muscularis propria and the adventitia with or without peritumoral malignant adenopathy, or T2 or T3 lesions with N0 or N1, N2, or N3 status, neoadjuvant therapy is the norm, although the optimal management remains controversial and treatment protocols vary around the world [3,62]. Most neoadjuvant therapy regimens in the United States combine chemotherapy and external beam radiation therapy.
Neoadjuvant treatment with chemoradiation has been found to be beneficial in all esophageal cancers [3,64]. A meta-analysis of 1209 patients found a significant survival benefit for preoperative chemoradiotherapy and, to a lesser extent, for chemotherapy when compared to surgery alone [65]. When comparing neoadjuvant chemoradiotherapy to surgery alone, there was a 19% decrease in the risk of death corresponding to a 13% absolute difference in 2-year survival in the neoadjuvant chemotherapy group. HR for all-cause mortality with neoadjuvant chemoradiotherapy versus surgery alone was 0.81 (95% CI, 0.70 to 0.93; P = 0.002). The benefits of neoadjuvant chemoradiotherapy were similar for both esophageal SCC and adenocarcinoma. The benefits of chemotherapy, however, were less than chemoradiotherapy. When comparing neoadjuvant chemotherapy to surgery alone, there was an absolute survival benefit of 7%.
Following neoadjuvant therapy, patients typically undergo restaging via cross-sectional imaging, most commonly PET/CT scans. If the patient is felt to have active residual disease and has not developed metastases or contraindications to surgery, esophagectomy is appropriate. Some data suggests that patients with esophageal SCC who have complete clinical response after chemoradiation can be observed closely rather than proceed to surgery [3,62,66]. However, the data concerning the usefulness of definitive chemoradiotherapy in esophageal adenocarcinoma is lacking at this time. In a retrospective study of nonmetastatic esophageal adenocarcinoma patients by Tougeron et al comparing surgical patients (± preoperative treatment) to definitive chemoradiotherapy patients, a complete resection was achieved in 92.5% of patients in the surgical group and a clinical complete response was observed in 49.4% of patients with definitive chemoradiotherapy [67]. The overall survival was 36.2 ± 2 months for the surgery group versus 16.5 ± 0.8 months for the definitive chemoradiotherapy group ( P = 0.02).
Stenting Prior to Neoadjuvant Therapy
Most patients with locally advanced esophageal cancer requiring neoadjuvant therapy have significant dysphagia [68]. Several studies have demonstrated that esophageal stenting prior to neoadjuvant treatment significantly improves patients’ dysphagia (see Figure 4 on page 376). A retrospective study of 55 patients by Siddiqui et al found that patients treated with fully covered self-expandable metal stents (SEMS) had significant improvement of dysphagia symptoms [68]. Patients in the study had a mean baseline dysphagia score of 2.4 ± 0.89. One week after stent placement, the mean dysphagia score was reduced to 1 ± 0.81 ( P = 0.001). Complications from stenting included chest discomfort and stent migration. In the study, 31% of the patients had stent migration; however, it was not associated with harm or injury to the patient and usually represented a positive response to neoadjuvant therapy. However, 1 patient did have delayed perforation.
In a meta-analysis of 9 studies comprising 180 patients, placement of esophageal stents in patients with locally advanced esophageal cancer significantly improved dysphagia and allowed for oral nutrition during neoadjuvant therapy [69]. There was a substantial decrease in the dysphagia scores standard difference in means (SDM) of –0.81 (standard error, 0.15; 95% CI, –1.1 to –0.51), an increase in weight SDM of 0.591 (standard error, 0.434; 95% CI, –0.261 to 1.442), and an increase in serum albumin SDM of 0.35 (standard error, 0.271; 95% CI, –0.181 to 0.881). The overall procedural success rate was 95% (95% CI, 0.895 to 0.977). Major adverse events included stent migration in 32% of patients (95% CI, 0.258 to 0.395) and chest discomfort in 51.4% (95% CI, 0.206 to 0.812). However, it was believed that the stent migration may have been a sign of tumor response to neoadjuvant therapy.