Lymph Node Classification May Help Prognosticate in Esophageal Cancer

"Survival incrementally improved with better lymph node response (none/partial/complete). This was independent of the response in the primary tumor and the same survival benefit was observed in all stratified categories of N status," according to Andrew Davies, MD.

Evidence of pathological lymph node regression following neoadjuvant chemotherapy and surgical resection in patients with esophageal adenocarcinoma appeared to be predictive of survival outcomes and recurrence and survival, according to a study published in The Journal of Clinical Oncology.

The study evaluated 763 patients and analyzed 17,930 lymph node samples. Investigators detailed several classifications of responses, including complete lymph node response with no residual tumor (8.1%), partial lymph node response with a residual tumor in 1 or more lymph nodes (20.3%), poor or no lymph node response (39.7%), or negative lymph node response with no tumor or regression (31.8%); these classifications were reported to have “superior discriminatory ability,” according to investigators.

Improved overall survival (OS) was observed in patients with a complete lymph node regression (HR, 0.35; 95% CI, 0.22-0.56), partial lymph node response (HR, 0.72; 95% CI, 0.57-0.93), and negative lymph node response (HR, 0.32; 95% CI, 0.25-0.42). Disease-free survival was also analyzed, with similar results occurring in those with a complete lymph node response (HR, 0.32; 95% CI, 0.20-0.51), partial lymph node response (HR, 0.76; 95% CI, 0.60-0.96), and negative lymph node response (HR, 0.31; 95% CI, 0.24-0.41).

“Survival incrementally improved with better lymph node response (none/partial/complete). This was independent of the response in the primary tumor and the same survival benefit was observed in all stratified categories of N status (N0,1,2-3),” Andrew Davies, MD, consultant oesophagogastric and general surgeon at Guys and St. Thomas’ NHS Foundation Trust said in a written statement to CancerNetwork^®.

The patient median age was 63 years, and most patients were male (86.2%). In terms of treatment with chemotherapy, 78.0% of patients received epirubicin, cisplatin, and fluorouracil/capecitabine (MAGIC); 11.7% received fluorouracil, oxaliplatin, leucovorin, and docetaxel (FLOT); 8.7% received cisplatin and fluorouracil (OEO2); and 1.7% received alternative therapy. Additionally, transthoracic esophagectomy was performed in 73.0% of patients, 23.5% received transhiatal esophagectomy, and 3.5% received extended total gastrectomy.

The chances of advanced pathological T-stage, lymphovascular invasion, or a positive resection margin occurring were less likely for patients who had a complete lymph node response or negative lymph nodes. Of note, patients who received FLOT neoadjuvant chemotherapy (38.2%) were more likely to have lymph node regression compared with the other regimens such as MAGIC (28.4%).

A pathological response in the primary tumor was observed in 42.2% of patients. Additionally, lymph node responses may also predict pathological responses in the primary tumor including complete lymph node response (78.7%), partial lymph node response (45.5%), and poor or no lymph node response (22.7%; P <.001).

Investigators noted that 22.5% of patients had a lymph node response without a primary tumor, and 23.2% of patients had a primary tumor but no lymph node response. Negative lymph node response was excluded and a lack of agreement between the primary tumor and lymph node response was observed in 32.1% of patients. Investigators reported missing primary tumor regression data in 1.3% of patients.

Patients with poor or no lymph node response had the highest rates of recurrence (66.7%). This occurred in patients who had locoregional and systematic recurrences. Moreover, the survival benefit was higher in those who experienced a pathological response in the primary tumor vs those with no response (Mandard 1; HR, 0.49; 95% CI, 0.27-0.91; Mandard 2-3; HR, 0.70; 95% CI, 0.55-0.87).

“We hope that lymph node regression will be incorporated into standard pathological reporting. With a move to more tailored therapies, markers of response will likely be used to guide adjuvant treatment. Lymph node regression is arguably a better marker of systemic efficacy than response in the primary tumor. This principle should be tested in other tumor groups,” Davies concluded.

Reference

Moore JL, Green M, Santaolalla A, et al. Pathological lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom. J Clin Oncol. Published online July 27, 2023. doi:10.1200/JCO.23.00139