Esophageal Cancer: Associations With (pN+) Lymph Node Metastases

Abstract

Objectives: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer.

Summary background data: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics.

Methods: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques.

Results: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones.

Conclusions: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Figure 1

Variable importance for each of the 31 variables from Random Forest analysis of pN status.

Figure 2

Frequency of pN+ according to G, pT, and histopathologic cell type (red=G1, green=G2, blue=G3). Key: adeno, adenocarcinoma; squam, squamous cell cancer.

Figure 3

Out-of-bootstrap predicted probability of pN+ cancer as a function of number of nodes resected, stratified by G, pT, and histopathologic cell type (red=G1, green=G2, blue=G3). Individual dots represent predicted probabilities and solid lines are LOESS (locally weighted scatterplot smoothing) values of predicted probabilities. Key: adeno, adenocarcinoma; squam, squamous cell cancer.

Figure 4

Probability of pN+ according to number of resected nodes and various esophageal cancer characteristics.

Figure 5

Predicted number of positive nodes according to number of resected nodes and various esophageal cancer characteristics.

Figure 6

Out-of-bootstrap predicted probability of pN0, pN1 (1–2 positive nodes), pN2 (3–6 positive nodes), and pN3 (7 or more positive nodes) cancers, stratified by G, pT, and histopathologic cell type (red=pN0, green=pN1, blue=pN2, turquoise=pN3). Key: adeno, adenocarcinoma; squam, squamous cell cancer.

Figure 7

Adjusted predicted probability of pN+ for various cutoff values of number of resected nodes, according to pT and cancer length. Where curves plateau is interpreted as the lymphadenectomy necessary to accurately detect pN+.