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Key Words

Esophageal cancer; fluorouracil; cisplatin; radiation therapy; surgery. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

In this randomized clinical trial, patients with esophageal cancer lived just as long after receiving chemoradiation therapy alone as did those whose chemoradiation therapy was followed by surgery.

Source

Journal of Clinical Oncology, April 1, 2007 (see the journal abstract).
(J Clin Oncol 2007 April 1; 25(10): 1160-1168)

Background

Cancer of the esophagus—esophageal cancer—can begin in two different types of cells. Squamous cell carcinoma begins in the cells that line the esophagus. Adenocarcinoma begins in the cells that produce mucus and other fluids. Both types of esophageal cancer have traditionally been treated whenever possible with surgery, which requires the removal or manipulation of delicate structures in the neck and chest and has a risk of treatment-related death.

Studies over the last decade have shown that giving chemotherapy and radiation therapy together (called chemoradiation therapy) before surgery can help patients with esophageal cancer live longer. Recently, researchers have wondered if chemoradiation alone could be an acceptable treatment for esophageal cancer, eliminating the need for risky surgery.

The Study

Between 1993 and 2000, investigators enrolled 444 esophageal cancer patients into this phase III clinical trial. Almost 90 percent of the patients had squamous cell carcinoma, and the rest had adenocarcinoma. All patients received radiation therapy and two cycles of chemotherapy with the drugs fluorouracil and cisplatin.

Radiation therapy consisted of either conventional radiation therapy (given five days a week for four and a half weeks) or split-course radiation therapy (given during days 1 to 5 and 22 to 26 of the initial therapy period), depending on the preference of the patients and their doctors. However, during the trial a separate study showed that conventional radiation therapy was more effective than split-course radiation therapy. From that point on, all newly enrolled patients received only conventional radiation therapy.

The researchers monitored patients’ response to the chemoradiation and then randomly assigned only those whose tumors had shrunk (259 patients) to either surgery (129) or further chemoradiation therapy that ended about three months after the start of treatment (130).

Patients were followed for a median of 47.4 months. The investigators used imaging and biopsies to track the progress of tumors. They then compared the severity of dysphagia (trouble swallowing), number of required trips to the hospital, location of cancer recurrence, quality of life, and overall survival between those who received surgery in addition to chemoradiation and those who received chemoradiation only.

The study was coordinated by the Fédération Francophone de Cancérologie Digestive (FFCD), in France. The paper’s lead author was Laurent Bedenne, M.D., from the FFCD.

Results

An interim analysis performed in November 2000 revealed that there was no statistically significant difference in survival between the two groups; the trial was then closed to further enrollment. Follow-up visits continued to show no difference in survival. Two years after starting treatment in the trial, 33.6 percent of those who’d received surgery in addition to chemoradition were still alive compared to 39.8 percent of those who’d received chemoradiation alone, a difference that could have occurred by chance.

More patients in the surgery group died from treatment-related complications, and more patients in the chemoradiation group had a recurrence of their tumor in or near the esophagus (called locoregional recurrence).

Patients in the surgery group spent significantly more time in the hospital during treatment, but patients receiving continued chemoradiation therapy required significantly more procedures to relieve trouble swallowing. Quality of life remained similar between the two groups after two years.

Limitations

Patients who received split-course radiation therapy received treatment that was “later demonstrated to be inferior to conventional” radiation therapy, stated the authors, which could have biased their results. Furthermore, even those patients receiving conventional radiation therapy had a two-week gap in their radiation therapy during the time that evaluation for randomization occurred.

However, explained Bhadrasain Vikram, M.D., chief of the National Cancer Institute’s Clinical Radiation Oncology Branch, “the fact that surgery failed to show a benefit even though the radiation therapy was suboptimal [for some patients] actually strengthened the conclusion that surgery wasn’t adding much in terms of survival. If the radiation therapy had been better, perhaps the tumor control with chemoradiation [alone] would have been even better.”

Comments

“This study suggests that therapeutic strategies with or without surgery result in similar survival rates for locally advanced thoracic esophageal cancer patients responding to chemoradiation,” conclude the authors.

“The evidence is fairly persuasive that surgery did not add a meaningful benefit for patients responsive to chemoradiation,” agrees Vikram, at least for the 90 percent of participants with squamous carcinoma. “Similar studies should be done in adenocarcinoma, because it’s probably a different disease, and it’s more common in the United States.”

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