Nodal Status Key to Outcome After Chemoradiation for Esophageal Cancer

DUBLIN, July16 -- For esophageal-cancer patients, a node-negative status after neoadjuvant chemoradiation is the best predictor of the outcome of surgery, researchers here found.

The finding is important because it shifts the focus from the primary tumor to the lymph nodes and may influence the way clinical trials are designed, according to John Vincent Reynolds, M.D., of St. James's Hospital and Trinity College Dublin and colleagues.

It also may help to clarify the "confused and conflicting" interpretations of randomized clinical trials of neoadjuvant chemoradiation therapy for esophageal cancer, Dr. Reynolds and colleagues reported in the May issue of Annals of Surgery.

Although clinicians widely believe there are patients for whom neoadjuvant chemoradiation therapy works well, identifying them is not easy, the researcher said.

To help clarify the issue, the researchers prospectively followed 243 patients treated with neoadjuvant chemoradiotherapy during 1990 to 2004, paying particular attention to the histomorphological tissue changes caused by the therapy. There were 170 patients with adenocarcinoma and 73 with squamous-cell carcinoma.

Patients were eligible for neoadjuvant chemoradiation if they met pre-set criteria, including being younger than 77, fit for surgery, and having a resectable tumor. They were given a standard protocol of radiation and chemotherapy with fluorouracil and cisplatin for eight weeks before undergoing thoracotomy with lympadenectomy and nodal dissection at week nine.

Thirty patients did not proceed to surgery but of the remaining 213, 41 (or 19%) had a complete pathological response to the pre-surgery therapy, meaning there was no sign of cancer in the tissue samples.

After a median follow-up of 60 months, median survival for the whole group was 18 months. But for the group of patients who achieved a complete pathological response, five-year survival was 50%, with median survival of 56 months.

"The achievement of a complete pathologic response following neoadjuvant chemotherapy alone or in combination with radiotherapy for esophageal tumors is a surrogate marker of survival advantage," the researchers said.

Patients with a complete pathologic response survived significantly longer (at P<0.001) than the nine months seen in the node-positive group.

But their survival was not significantly greater than the 37 months achieved by node-negative patients, the researchers found. Indeed, the best outcome was seen for the 69 patients with a complete response who were also node-negative -- a median survival of 67 months and five-year survival of 53%.

Also, Dr. Reynolds and colleagues said, there was no difference in one-year and three-year survival between patients who had a complete pathological response and those who were node-negative after treatment.

In a univariate analysis, the researchers found, both nodal status and tumor regression grade were significantly associated with overall survival, but in a multivariate analysis the only prognostic variable that remained significant was nodal status (P=0.002).