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Preoperative Therapy in Patients with Esophageal Cancer

Preoperative chemotherapy plus radiotherapy improves survival.

Esophageal cancer is rare but virulent and is the seventh-leading cause of cancer-related deaths in American men. Squamous cell carcinoma (SCC) is more common in people of African and Asian descent, whereas adenocarcinoma of the esophagus predominates in whites and is increasing in incidence. Survival after surgery alone for locally advanced esophageal cancer of either type is poor, ranging from 20% to 40% at 5 years. Older studies of preoperative chemotherapy or chemoradiotherapy in conjunction with surgery in esophageal cancer patients failed to show a clear overall survival benefit. However, many of the studies were small and statistically underpowered to detect modest survival benefits with adjuvant therapy.

Researchers now report results from a large meta-analysis of randomized trials in which surgery alone was compared with surgery plus either preoperative chemotherapy or chemoradiotherapy for locally advanced esophageal SCC and adenocarcinoma. The primary endpoint of the analysis was all-cause mortality, and secondary endpoints were treatment outcomes in the adenocarcinoma and SCC subsets. Data from 10 trials of neoadjuvant chemoradiotherapy (1209 patients) and 8 trials of neoadjuvant chemotherapy (1724 patients) were included in the analysis. The most common chemotherapy administered was cisplatin plus continuous-infusion 5-fluorouracil (5-FU). Individual and updated patient data were available for several of the trials.

Preoperative chemoradiotherapy resulted in a significant 19% reduction in mortality risk (hazard ratio, 0.81; 95% confidence interval, 0.70–0.93). A greater survival benefit was seen among patients with adenocarcinoma (HR, 0.75) than among those with SCC (HR, 0.84), probably because, in early SCC trials, less-effective sequential combination therapy, rather than concurrent chemotherapy and radiotherapy, was administered. Preoperative chemotherapy resulted in a 10% reduction in mortality risk (HR, 0.90; 95% CI, 0.81–1.00; P=0.05), with benefit seen only in patients with adenocarcinoma (not SCC). The absolute improvement in 2-year survival was 13% for preoperative chemoradiotherapy and 7% for preoperative chemotherapy.

Comment: Most oncologists no longer accept the idea that surgery alone is adequate treatment for esophageal cancer, because recent trials indicate a survival benefit for both preoperative chemotherapy and preoperative combined chemoradiotherapy. This large meta-analysis supports a survival benefit for patients who receive preoperative therapy, and it affirms recently published results from a phase III trial of preoperative chemotherapy for adenocarcinoma of the esophagus and stomach (N Engl J Med 2006; 355:11). The data for preoperative chemotherapy for SCC remain less compelling; the standard of care is a combination of concurrent chemotherapy and radiation therapy, either as primary treatment without surgery or followed by surgery. Although the role of adding radiotherapy to preoperative chemotherapy remains controversial in adenocarcinoma, this combination increases rates of curative resection and pathologic complete response compared with neoadjuvant chemotherapy alone. The results of this meta-analysis support combination preoperative chemotherapy and radiotherapy over preoperative chemotherapy alone in treating adenocarcinoma of the esophagus.

— David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology July 9, 2007

Citation(s):

Gebski V et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: A meta-analysis. Lancet Oncol 2007 Mar; 8:226-34.

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