According to a new study, the status of lymph nodes rather than the status of the primary tumor following preoperative neoadjuvant chemotherapy or chemoradiation therapy is the most important factor that determines whether patients with locally advanced esophageal cancer will survive. The study presented at the American Association for Thoracic Surgery's 98th Annual Meeting indicates that while preoperative chemotherapy and radiation therapy improve the survival of patients with esophageal cancer, patients with malignant lymph nodes following therapy were less likely to survive than patients with no cancer in the lymph nodes.
Nearly half a million patients worldwide are diagnosed with esophageal cancer each year, and its incidence has doubled in the US in the last 20 years. The combination of chemotherapy with or without radiation therapy followed by surgery with negative margins offers the best chance for long-term survival for patients with locally advanced esophageal adenocarcinoma. Preoperative neoadjuvant therapy – chemotherapy and/or radiation therapy before surgery – is frequently administered. Importantly, the tumor's response to this initial treatment has the potential to help guide further therapy.
"There is a clear benefit associated with esophagectomy as part of a multimodal treatment strategy, along with chemotherapy with or without radiation therapy. for patients with locally advanced esophageal adenocarcinoma," explains Shawn S. Groth, MD, MS, FACS, Assistant Professor, Baylor College of Medicine, Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Houston, who led the study and presented the findings at the AATS meeting. "However, there has been little clinical evidence to predict which patients might benefit."
Therefore, investigators set out to describe disease response rates (no, partial, or complete response) associated with the use of neoadjuvant chemotherapy or chemoradiation therapy to evaluate the association between the degree of pathologic response and overall survival, and to characterize the relative impact on survival by evaluating the response of the primary tumor versus the response of the lymph nodes to initial therapy.
Investigators reviewed records in the National Cancer Database of nearly 3,000 patients aged 18-80 who were diagnosed between 2006 and 2012 with clinically staged, locally advanced esophageal adenocarcinoma, and who had received neoadjuvant chemotherapy or chemoradiation therapy followed by an esophagectomy with negative margins.
Of the patients in the study, 17.3 percent had a complete response and 34.5 percent had a partial response to neoadjuvant therapy. Compared with neoadjuvant chemoradiation, neoadjuvant chemotherapy was associated with lower primary tumor (21.3 percent vs. 33.9 percent) and nodal response rates (32.7 percent vs. 55.9 percent) and was less likely to achieve a partial or complete response.
Significantly, the study found that as the completeness of response increased, survival rates improved. It also determined that patients who still had cancer in lymph nodes after preoperative chemotherapy and radiation therapy, independent of how well the tumor responded to treatment, had worse survival rates than patients who had no cancer in their lymph nodes.
Pathologic nodal, rather than primary tumor, response to neoadjuvant therapy is associated with improved survival. These data suggest a need to optimize neoadjuvant strategies associated with more complete nodal response rates and to consider more aggressive adjuvant treatment for patients with residual nodal disease after esophagectomy.
According to Dr. Groth, "Given the aggressive nature of esophageal cancer, our inability to predict which patients will respond to neoadjuvant therapy, and the morbidity associated with surgical resection which currently limits the number of patients who are able to receive adjuvant treatment, certain patients with locally advanced esophageal adenocarcinoma may also benefit from this 'total upfront" approach prior to esophagectomy."
These findings could be used to help physicians counsel patients about their prognosis and determine which patients may benefit from additional chemotherapy before or after surgery.