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The new, 7th Edition of the TNM (tumor, nodes, metastases) staging system for lung cancer came into use earlier this year and has led to changes in the staging of about 15% of lung cancers compared with what they’d have been staged as under the 6th edition. Under this new system, some patients have been upstaged: patients with 2.2 cm node-negative lung cancer are now considered T1b instead of T1a, and patients with a 5.5 cm node-negative cancer have an overall stage of IIA instead of 1B. On the other hand, others are downstaged, so that people with additional nodules in the same lobe as a primary tumor are now stage IIB instead of IIIB, and those with other nodules in different lobes of the same lung are now considered stage IIIB instead of stage IV.
The problem is that this leads to a gulf between the evidence produced with an older staging system and how to direct treatment for people today. The staging system is designed to stratify the prognosis — how long we expect a group of people to live — for people with lung cancer; it isn’t specifically designed to define the treatment that people should receive, though there are general guidelines that emerge largely based on stage. Nevertheless, a recent publication in the Journal of Thoracic Oncology confirms what I’ve been seeing pretty commonly from referrals to my fractive or comments here on the discussion forum. Clinicians are very often changing treatment recommendations based on the new stage, even though the biology of the cancer in 2010, under the 7th edition of the lung cancer staging system, is the same as it was under the 6th edition. Specifically, 77% of physicians surveyed at a series of recent lung cancer meetings indicated that they would change the treatment recommendations for a patient based not on the underlying characteristics of the cancer but by the overall stage that this translated as.
At this year’s ASCO meeting, I had the opportunity to review and provide commentary on several presentations from other researchers, all on the topic of how to refine our ability to predict how patients will do after surgery for stage I – IIIA NSCLC, with an idea that this information can help guide decisions about who should receive chemo and who shouldn’t.
One of the interesting abstracts came out of Japan, where a group of investigators led by Dr. Matsuguma looked details about the surgical results and long-term outcomes of 574 patients who all underwent surgery at a single center, asking the question of whether the number of lymph nodes involved with cancer is important for prognosis, and specifically whether this variable might be more important than the location of the lymph nodes in its correlation with prognosis (abstract here). Our current system of assigning node stage is based not on number of lymph nodes but rather where any nodes with cancer happen to be. Lymph nodes in the same lung as the cancer are called N1, while nodes outside of the lung and in the middle of the chest are designated as N2 on the same side of the chest as the main cancer, or N3 on the opposite side. Lymph nodes above the clavicle are also considered N3. This staging from N1 to N2 to N3 is somewhat associated with worse prognosis, primarily because involved nodes further from the cancer are associated with a greater risk of spread of the cancer to distant parts of the body. A lung cancer generally needs to have some ability to spread to get out to N2 or N3 nodes, and that’s associated with a higher likelihood of recurrence outside of the local area of the chest.
The group recognized that at the time of surgery it can be hard to know which nodes came from what exact area, and also that sometimes we see “skip nodal metastases” in which N2 or N3 nodes are involved without any N1 nodes involved, which you wouldn’t expect to happen with a stepwise escalation of aggressiveness. They also thought it might matter whether one lymph node is involved or multiple nodes is involved in a given location. So they looked at the question of whether you could do a better job with the current system that uses nodal location by also adding information about how many nodes were involved. And they found that compared with the current system (left side of the figure below, with little separation of the N1 vs. N2 groups, so not great at offering prognostic information), adding information about the number of either N1 nodes involved (4 or fewer vs. more than 4; upper curve on right) or N2 nodes involved (6 or fewer vs. more than 6; lower curve on right) could help stratify the prognosis for both groups, providing a clear separation of a better and a worse subgroup):