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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)


Assessing the "flight risk" of a lung cancer: Why we care so much about lymph nodes
Howard (Jack) West, MD

Why do we care about lymph nodes when staging lung cancer?

The simple answer is that they give us prognostic information (insight into the likely future behavior, the "natural history", of the cancer). When you think of a cancer's growth, there are a few potential ways for it to progress. It might progress right where it started, staying local. It might travel through the lymphatic system, kind of like debris swept off a roof and into a home's gutter, and it might spread distantly to other parts of the body. We're interested in getting a sense of how aggressive a cancer is likely to be overall, the engine behind its growth, but also whether it's more likely to stay local or travel distantly.

The staging system for lung cancer and most others is called the TNM system, where T stands for Tumor stage (the primary cancer, where it started), N stands for Nodal stage (are lymph nodes involved, and if so, where?), and M stands for Metastasis stage (distant metastases, yes or no?). The M stage overrides the others -- if a cancer has spread to distant parts of the body, it's an advanced cancer, no matter how big or small the primary tumor or whether there are lymph nodes involved or not. But N stage is also quite important.

Essentially, the distance from the primary cancer to any involved lymph nodes, along with the number of lymph nodes that have cancer within them, help predict the probability that the cancer is able to get out of the area in which it started and spread to distant parts of the body, where cure is generally not something we can expect to achieve. Lymph nodes within the same lung as the primary cancer are called N1, and those in the mid-chest (mediastinum) between the lungs are called N2 if on the same side as the primary tumor, or N3 if on the other side or above the collarbone (lymph nodes outside of the chest are unfortunately considered metastatic sites, because they almost always occur in the setting of more widespread progression).

This numeric staging reflects the distance the cancer had to travel to get there, so higher number for N stage means greater distance and greater chance of spread to other parts of the body, and the stage is often dictated by the highest N stage seen, unless there is distant metastatic disease (which, as noted above, overrides other considerations and denotes metastatic/advanced cancer).

Basically, nodal status assesses the probability of a cancer to travel further, even if you don't see evidence it has metastasized yet. It's kind of like when my youngest son had wandered out onto the driveway after figuring out how to unlock the front door, open it, and walk outside. He didn't quite wander into the street, but he had clearly shown that he had the skills to escape. Imagine that N1 nodal involvement is like finding him having unlocked the door, N2 is like opening it and starting to look outside, and N3 is like him walking down the driveway toward the street. (He is now 7 and at far more risk of video-game induced brain rot.)

While the number of lymph nodes involved is not formally part of the staging system, there are many studies over the years that have shown that prognosis is more favorable if one or a few lymph nodes are involved by cancer vs. many nodes involved. Lymph node involvement that is only microscopic has a more favorable prognosis than involvement that leads the nodes to become enlarged (as I think you would expect). And lymph node involvement by "direct extension" of a primary tumor just growing into an adjacent lymph node tends to be associated with a more favorable prognosis than having one or more lymph nodes involved by the usual method of traveling through the lymphatic system, so there is some space between the primary cancer and the involved nodes.

How does this change our management? Aside from providing important information about the probability of cure, such as the probability of the cancer recurring after potentially curative surgery or chemo and radiation, it helps provide clues about the relative weight we might want to give to chemotherapy vs. "local" treatments like surgery and radiation. For example, a cancer that shows a pattern of a 4 cm primary tumor but no lymph node involvement has provided a clue that it's going to stay local and not be at as high a risk for distant spread as a cancer that is 3 cm but has spread to mediastinal lymph nodes on the same side as the primary tumor. The latter might possibly be treated with surgery, but chemotherapy is going to be a strong recommendation for just about any patient with N2 or higher node involvement, and it's standard to recommend chemotherapy to reduce the risk of recurrence after surgery for a resected cancer with N1 (within the lung) node involvement, but not as clearly needed for someone with the same cancer but no lymph nodes involved.

For locally advanced (stage III) non-small cell lung cancer, lymph nodes are critical in selecting an optimal treatment. A single N2 node is in the realm that many experts would consider perfectly appropriate for surgery, but multiple N2 nodes or any N3 disease puts it in the range in which surgery is generally not favored. Instead, chemo and radiation are typically favored. This isn't because we can't find a surgeon to try to remove all visible disease, but rather that both multiple N2 nodes and N3 nodal disease represent a situation in which we need to concentrate on more than just the disease we can see. We need to be sure to cast a wide net to treat the disease we can see and the disease we can't. Radiation treats a broader local area than surgery, as a general rule, and we can more reliably get in a meaningful amount of chemo when someone hasn't just undergone a major lung surgery.

This is a big topic, so I'd welcome your questions. There are always individual circumstances, but I wanted to provide a general sense of why nodal status matters and how we use this information to prioritize one treatment approach over another. I hope that helps.

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