Lymph Node Response Can Prognosticate Long-Term Survival in Patients With Esophageal Cancer

Researchers in Japan have established that, in patients with metastatic esophageal cancer, lymph node response to neoadjuvant chemotherapy more accurately predicts long-term survival than primary tumor response (Ann Surg. 2019 Jul 3. Epub ahead of print).

Tomoki Makino, MD, PhD, Assistant Professor, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan, spoke with Oncology Learning Network about what led to this research and the clinical significance of these findings.

What existing data led you and your co-investigators to conduct this research?

Neoadjuvant chemotherapy followed by surgery is currently a standard strategy for treating advanced esophageal cancer. Although the response to neoadjuvant chemotherapy is considered an important determinant of survival in esophageal cancer patients, optimal methods for evaluating treatment efficacy in patients with esophageal cancer have not been established.

Therefore, we urgently need to establish an accurate response evaluation method for predicting prognosis in patients with esophageal cancer to achieve treatment optimization strategies for each patient.

Although imaging techniques such as computed tomography (CT) and endoscopy are often used to examine primary tumors in cancer patients, these techniques are not helpful when trying to measure primary tumors in the esophagus because of its shape. Thus, it is difficult for physicians to estimate recurrence and survival in patients with esophageal cancer.

Therefore, our team attempted to address this issue by finding another indicator of patient outcome by targeting metastatic lymph node, which is frequently identified in esophageal cancer patients, as a “measurable” organ for response evaluation.

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising?

In this study, we used CT scan to evaluate the chemotherapeutic response by monitoring the respective sizes of primary tumors and all metastatic lymph nodes that met a specific set of criteria before and after neoadjuvant chemotherapy in individuals with metastatic esophageal cancer.

Surprisingly, our result demonstrated the high discordance in the response between primary tumors and metastatic lymph nodes in patients with esophageal cancer. Compared with primary tumors, which are often used to assess treatment outcomes in many types of cancers, the response of lymph nodes to neoadjuvant chemotherapy as measured by CT was more effective and accurate in predicting disease recurrence and patient survival in individuals with esophageal cancer.

What are the possible real-world applications of these findings in clinical practice?

Our method of evaluating all positive lymph nodes by CT scan is simple and basically based on RECIST criteria. In addition, the frequency of lymph node metastases is very high, particularly in patients with advanced esophageal cancer versus other gastrointestinal cancers.

Therefore, our method of response evaluation in positive lymph nodes is feasible and applicable in most cases of advanced esophageal cancer in any institutes and are likely to enhance the accuracy of predictions regarding treatment outcome, and may contribute to optimizing treatment strategies in patients with metastatic esophageal cancer as follows: patients with ≥30% size reduction in all lymph nodes after neoadjuvant chemotherapy undergo surgery right away whereas patients with <30% size reduction better receive neoadjuvant chemotherapy with different regimen or chemo-radiation before surgery to improve their long-term survival.

Do you and your co-investigators intend to expand upon this research?

Future studies should explore the optimal response evaluation for patients with node-negative esophageal cancer, to establish personalized treatment for all patients with esophageal cancer.

Additionally, future studies should evaluate the feasibility of targeting distant metastatic lesions, in addition to lymph nodes in patients with esophageal cancer. It would be also interesting to see if this finding can be applicable in response evaluation of neoadjuvant chemo-radiation for patients with esophageal cancer, too.