If you’re at all familiar with cancer, you’ve likely heard the term “stage” thrown around quite a bit. If you’re like me, you probably haven’t spent too much time questioning it; I simply assumed that as the stage goes up, things get worse. But when I was asked in depth how cancers are staged, something I assumed would be relatively straightforward, I struggled to answer it. As I dove deeper into how cancer is staged, I ran into a lot of nuance. Different types of cancer are staged differently; whether the tumour is solid or liquid changes staging; and, perhaps most importantly, what each stage means in terms of outcome changes completely for different cancers. So, I thought it would be a good idea to break down how cancer is staged, at least in Canada and the US, and what that means for the outcome of different cancers

In Canada, most cancers are graded with something called the “TNM Staging System”. This system uses three different variables: T, N, and M, in combination, to put the cancer into one of four stages. The system starts with T, which stands for “tumour”. T describes the literal size of the tumour; how big or how small. When clinicians take pictures of tumours, they’ll look at how big it is and assign it a T value, usually from 0-4. The bigger the number, the larger the tumour.

Next comes N, which stands for “Nodes”, the lymph nodes, to be precise. N describes whether the cancer has spread to lymph nodes around the organ it came from. The value of N, which is usually from 0-3, describes the extent to which the cancer has invaded the lymph nodes.

Finally, we have M, which stands for “metastasis”. M can be either M0 or M1, and it describes whether or not the cancer can be found in other parts of the body.

The combination of these three variables is what helps physicians classify a cancer as stage I, II, III, or IV. In other words, stage is determined by the size and spread of the cancer. One important factor to consider for solid tumours is their M score. In many cancers, including prostate, lung, breast, and others, if the cancer has spread, which means the cancer is M1, they’re classified as stage IV. Stages I-III are all different combinations of size and involvement with the lymph nodes, but they have not spread.

Not quite… unfortunately, there’s a lot more nuance to this. For starters, you can’t use the TNM staging system for all cancers. Take a look at brain and spinal cord cancer, for example. If a tumour appears in the brain or spinal cord, it’s already in the most dangerous spot. These cancers very rarely metastasize because they’re already so deadly exactly where they are. So, the TNM staging system, which largely relies on whether the cancer has spread to the lymph or distant parts of the body, isn’t helpful. This system also doesn’t work for cancers that aren’t solid, which includes blood cancers. It’s really challenging to say how big a cancer is if it’s flowing through the blood. It’s also hard to classify if the cancer has spread to distant parts of the body if it’s circulating everywhere already.

So, for cases like this, the staging is more specific to the type of cancer. Brain and spinal cord cancer relies largely on characterizing the behaviour of the cell. Clinicians ask questions like “are the cells slower growing?” or “do they have a specific mutation that makes them more aggressive?” For liquid cancers, like leukemia, a cancer of white blood cells, clinicians often look at the number of cancer cells in the blood as a measure of disease progression. So, although the TNM staging system is helpful and commonly used for solid tumours, it can’t accurately classify all cancers, so clinicians go with more specific classifications.

At this point, you might be asking yourself “what does the stage actually mean for outcomes?”, and unfortunately, the only good answer for that is “it depends”. The prognosis and life expectancy change with each stage depending on the cancer. To look at this, we’re going to use 5-year net survival between prostate cancer and non-small cell lung cancer. This metric looks at the percentage of people who survive past 5 years after diagnosis. For prostate cancer, if an individual is diagnosed in stage I, II, or III, they effectively have a 100% 5-year net survival. That means that we’d expect everyone diagnosed with stage I-III prostate cancer to live past 5 years. For non-small cell lung cancer, the 5-year net survival is completely different. The 5-year net survivals for stage I-III for non-small cell lung cancer are 62%, 39%, and 16%. Despite using the same staging system, the outcomes may be completely different for the same stage of different cancers. This speaks to the nuance of staging, and to the importance of understanding the implications the stage has on the specific cancer you’re interested in. Not to mention that we haven’t even mentioned grading… but maybe soon. Although it can be a complicated metric, it can help tell you about the progression of a disease. We just have to make sure that we consider the stage in a relevant context.

I hope you learned a little something this week, but next week we’re going beyond cancer itself to discuss how the microbes in our body help or hinder cancer progression.

See you next week!

If you missed last week’s letter, you can read “Building A Better Immune Cell” to learn a little more about what cancer is and how it works.