Instead of Staging, ‘Count the Number of Metastatic Lymph Nodes’

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In patients with solid tumors, the simple process of counting the number of metastatic lymph nodes (LN) offers the best predictor of mortality, a new analysis shows.

It turned out to be better than more complicated processes involved in staging the lymph nodes, which involves examining the size of each node, its location, and how far the cancer has spread beyond the lymph node. These factors are highly variable, depending on the cancer site in the body, the researchers explain.  

They found a “universal and powerful association” between the number of metastatic lymph nodes and mortality across common solid tumors. “Mortality risk increased continuously with increasing number of positive lymph nodes across all disease sites without exception.”

The message is simple: “Count the number of metastatic lymph nodes,” commented  co-lead investigator Zachary Zumsteg, MD, assistant professor of radiation oncology, Cedars-Sinai Medical Center, Los Angeles, California.

“We found that this simple process is much better for determining prognoses for solid tumors than all the other factors used today. It should be the backbone of nodal staging because it is the best predictor of mortality, irrespective of the disease site,” he said in a statement.

The study was published in the Journal of the National Cancer Institute.

Approached for comment, Thomas Daniels, MD, service chief in the department of Radiation Oncology, Perlmutter Cancer Center–Sunset Park, New York City was in agreement.  

“This article evaluates for multiple disease sites the number of involved nodes specifically and finds the strongest correlation with this metric vs other variables for overall survival,” Daniels told Medscape Medical News.

“This is consistent with first principles used in a number of staging systems prioritizing numerical nodal involvement with higher nodal involvement inversely with survival,” added Daniels, who was not involved with this research.

Improved Patient Management

The study involved a retrospective analysis of 1.3 million patients from the National Cancer Database who had undergone surgery between 2004 and 2015 for 16 solid cancer sites, as well as roughly 2 million additional patients from the SEER registry.

The investigators found that patient mortality risk increased continuously with increasing number of positive lymph nodes across all disease sites without exception.

High quantitative lymph node burden also had the highest independent correlation with mortality of any tumor-intrinsic factor, including T classification, grade, and lymphovascular invasion, in 12 of 16 solid tumors, they report.

“These findings are significant because they can potentially improve and simplify how most solid cancers are staged,” lead author Anthony Nguyen, MD, PhD, a resident in the Department of Radiation Oncology at Cedars-Sinai, said in the release.

“Lymph node counting is possible in virtually all medical settings, including resource-poor countries, without increased cost to the provider or patient. It also is objective and concrete — almost all pathologists can look at lymph nodes and agree about how many are cancerous,” Nguyen said.

“Therefore, using nodal count as a backbone of nodal staging across solid cancers can streamline patient staging, create more consistency from cancer to cancer, and in some cases, improve the accuracy of prognostication over current systems,” the investigators wrote in their article.

This nodal staging process may also improve management of cancer patients.

“Nodal stages inform whether head and neck cancer patients, for example, are treated with surgery, chemotherapy or radiation, or all three,” Zumsteg said. “It is a major factor that guides treatments across all cancers. Improving staging can improve these treatment decisions.”

This research was supported in part by Cedars-Sinai Cancer. Zumsteg, Nguyen and Daniels report no relevant financial relationships.

J Natl Cancer Inst. Published online March 21, 2022. Abstract

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