# The Prognostic Role of Lymphadenectomy during Esophagectomy for Esophageal Cancer with Complete or Near-Complete Tumor Response after Neoadjuvant Therapy

## TL;DR

This study examines whether removing more lymph nodes during surgery improves survival for esophageal cancer patients who responded well to initial treatment.

## Contribution

The study evaluates the impact of lymphadenectomy extent on survival in complete or near-complete responders to neoadjuvant therapy for esophageal cancer.

## Key findings

- More extensive lymphadenectomy was associated with lower 5-year mortality in near-complete responders in the main cohort.
- The survival benefit disappeared when considering stage purification bias in a broader cohort.
- Results were consistent for both all-cause and disease-specific mortality.

## Abstract

The prognostic role of lymphadenectomy during esophagectomy for esophageal cancer in complete responders to neoadjuvant therapy is uncertain. This study aimed to help clarify this question.

This was a bi-national population-based cohort study in Sweden (2006–2024) and Finland (2006–2019). The main cohort included 515 patients with esophageal cancer who underwent esophagectomy after complete or near-complete tumor response without lymph node metastasis following neoadjuvant therapy. A secondary cohort included 669 patients with similar tumor response, regardless of nodal status. Data came from medical records and national health data registers. Associations between lymphadenectomy (categorized in quartiles) and 5-year mortality were assessed using multivariable Cox regression, yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, country, comorbidity, type of neoadjuvant therapy, calendar year, tumor histology, hospital volume, tumor location, tumor response, and T stage.

In the main cohort, comparing the highest quartile of lymphadenectomy (≥ 27 nodes) with the lowest (0–11 nodes) indicated decreased 5-year all-cause mortality (HR 0.54, 95% CI 0.34–0.88). Stratified analyses suggested no significant association for complete responders (HR 0.68, 95% CI 0.39–1.16), but for near-complete responders (HR 0.32, 95% CI 0.14–0.72). The associations disappeared when assessing stage purification bias in the secondary cohort (n = 669), with the corresponding HRs of 0.91 (95% CI 0.63–1.32) for all responders, 1.01 (95% CI 0.61–1.66) for complete responders, and 0.79 (95% CI 0.47–1.33) for near-complete responders. Results were similar for 5-year disease-specific mortality.

After considering stage purification bias, more extensive lymphadenectomy did not improve the long-term survival among patients with complete or near-complete tumor response after neoadjuvant therapy.

The online version contains supplementary material available at 10.1245/s10434-025-18599-6.