Episode 39 Shownotes - Understanding Metastatic Disease
Well, hey friends. Hope this finds you well. We are having a winter with a LOT more snow than the last few years! I have really enjoyed some snowy walks with my dogs, along with some sledding and skiing with my kids, which has really been fun. But, it keeps snowing during the week! This leads to challenges getting to work, and school being cancelled. So funny, our family in Wyoming say that school is never cancelled for snow, but yet here in NJ, it is whenever we get more than 4-5 inches. And we have seen what happens when Texas gets snow – everything screeches to a halt. Hope all of you in that part of the US are haning in there! Interesting how things vary across the US, right? My friends in the Carolinas say that school is cancelled even if they are predicting snow! One of the things about working in oncology, man, many of my patients manage to get to treatment even in blizzards! So I do everything I can to get to work safely so that I can take care of them. I guess what I am saying is I wish I had an “Easy” button for weather, where it only snowed on the weekends.
We all want the easy button in life, don’t we? So much of cancer care is NOT easy for patients or their families. There is so much to learn, so much people don’t understand. I have had a lot of questions about one of the hardest things lately, so I thought it was time for a science podcast to teach a bit. Today we are talking about metastatic disease. This is going to be a forthright discussion, so if you have been diagnosed with metastatic disease, take a minute to think about how much information you want. If you feel like knowledge is power, this will really help you understand a bit better. If more information is overwhelming, then maybe this is one you skip.
For starters, what is metastatic disease – what does that term actually mean? Metastatic disease is also known as Stage IV cancer. It is when a tumor spreads from where it started to distant sites elsewhere in the body. Cancer cells can spread in 2 ways. The first is by direct invasion into the bloodstream. The cells can develop the ability to worm their way into the vessels and travel elsewhere in the body and set up shop. The second way cancers can spread is via the lymphatic system. Tumor cells can invade the lymphatic channels and from there, travel to the lymph nodes, where they get filtered out. Sometimes they get stuck in the node and start to grow there, and sometimes they invade into the bloodstream to spread elsewhere from there. This is why chemo may be recommended in some cancers even though lymph nodes are negative, and explains why people with no nodal involvement at diagnosis can develop metastatic disease. While every cancer is different, the most common places to find spread are the liver, lungs and bones. This is because the very small vessels in these areas lead to the cancer cells getting trapped there.
One of the things I think is very important to understand when we talk about cancer staging is nodal spread and what it means. For most cancers, the regional lymph nodes are not considered distant spread. For instance, in breast cancer, the lymph nodes in the underarm, called the axillary nodes, or nodes between the ribs, called the internal mammary nodes, are considered local disease (sometimes referred to as locally advanced breast cancer). The same is true with lung cancer, colon cancer, head and neck cancer and more. So if you have spread to the lymph nodes, it is very important to confirm with your doctor whether or not this is local disease or metastatic disease. Don’t assume that just because you have disease in the nodes, you have stage IV cancer!
For the majority of people, when a cancer has spread from where it started to elsewhere in the body, it is no longer curable. There are some exceptions to this, though, so clearly discuss this with your team. For example, Stage IV lymphomas, seminomas, colon cancers with very limited sites of spread among others, are cancers where cure is possible. But, just because a cancer is not curable does not mean it is not treatable. The goal in patients with metastatic disease is twofold. Both extending their life and improving their quality of life are both goals that should be considered with therapy. For many cancers, we have multiple effective regimens for treating metastatic disease, and many types of metastatic cancer that were rapidly fatal 10 years ago now have survivals measuring in years, not months. I personally have a number of patients who are more than 10 year survivors with metastatic breast cancer and had a family member who was a more than 5 year survivor of metastatic lung cancer. So much of this is individualized, though, so open and honest discussion with your team is imperative. Based on where a tumor has spread, what the primary site is, whether there are targeted treatments that will be effective, survival can vary greatly. Most doctors can give a good guess at whether you are looking at 5 years, 1-2 years or less than a year, so if you want that information, ask.
When we are talking about metastatic disease, one of the things a lot of people question is why we don’t do surgery for the site of metastatic disease. That is rarely done in very specific cases, but in the majority of patients, just treating one site is ineffective. The reason for this is what I call my “dandelion” analogy. In the spring, at some point, you may drive past your lawn and see one or two dandelions. We often have an inclination to want to just pluck the ones we see, but experience has probably told you that if you don’t treat your yard, more will pop up. Metastatic cancer is the same. When we just treat one local site in the vast majority of cases, more places will pop up in short order. This is because even if we can see only one site, often there are small numbers of cells in other places waiting to set up shop. For this reason, systemic therapy is commonly the primary treatment of metastatic disease.
Systemic therapy can take many forms. One of the most common things in breast cancer is the use of hormonal therapies first. These block the estrogen and progesterone receptors on cancer cells and inhibit growth. This can be in pill form or injected. Hormonal therapy is also the first line treatment in most metastatic prostate cancers, with both pills and injected medications. Hormonal therapy is also sometimes used in uterine cancer. These are our first choice if an option, because they have the least side effects with excellent effectiveness in many cells. Often at some point after being on hormonal therapy for a time, the cancer cells mutate and no longer are hormonally dependant, which means the hormonal therapy is no longer effective. Some types of breast cancers are not hormonally sensitive from the start (ER and PR negative). In these cases, hormonal therapy will not be effective. Similar to hormonal therapy is targeted therapy. Targeted therapies are similar to hormonal therapies in that they interfere with specific molecules on or in the cancer cell involved in the growth, progression or spread of the cancer. Targeted therapies are deliberately designed to interact with their target. This means the cancer cells have to have the target for the medication to be effective. You might hear doctors refer to this in doctor speak as “actionable mutations”. What that means is that the cancer cell has a mutation AND we have a drug designed to target it. Development of these drugs is an example of “Rational” drug development, which means we need to pick targets that play a key role in cancer cell growth and survival, and then design a treatment that specifically acts on that target. In breast cancer, a commonly attacked target is the Her 2 Neu receptor, and there are a number of medications that act on this, with some of the earlier ones being Herceptin and Perjetta. The Her 2 receptor is present on some normal cells, including ones in the heart, but is present in higher concentrations on some breast cancer cells. We are going to get super science-y here for a minute – if this sounds like Greek, close – more Latin derived. But I will go through quickly and then get back to some easier to understand stuff. The major classes of targeted molecules include hormone therapy, as mentioned, along with signal transduction inhibitors that block a cell responding to signals in its environment. These include cetuximab or Erbitux, along with others that act on the EGFR pathway. Next are gene expression modifiers, which slow down or speed up how a gene is being used to produce proteins, apoptosis inducers, which increase programmed cell death, where abnormal cells purposely kill themselves off, angiogenesis inhibitors, which blocks the formation of new blood vessels to supply the tumors, immunotherapies, which trigger the immune system to destroy cancer cells. Keytruda is a type of immunotherapy used on a specific pathway in some lung cancers, melanoma, head and neck cancers and more. A branch of immunotherapy is monoclonal antibodies that recognize molecules on the surface of cancer cells and help our cells attack them better. These monoclonal antibodies can also be designed to deliver chemotherapy or radioactive substances to help kill the cell. So, what all this means is that this is a place where there is huge work being done, and new molecules are identified all the time, with more and more targeted drugs on the horizon.
Targeted therapy is different from chemotherapy in several ways. Targeted therapies act on specific targets in cancer cells, whereas chemotherapy acts on all rapidly dividing cells – both normal and cancer cells. Targeted therapies often stop growth and proliferation (a fancy word meaning spread) but are unable to kill cells. Chemotherapy is cytotoxic, which means kills cells, but does this to both normal cells and cancer cells. Targeted therapies are our second choice for many cancers. This is because, while there may be side effects from them, it is less severe than chemotherapy. Chemotherapy is usually reserved for after targeted therapy stops working, although occasionally they will start with chemotherapy first if they want to decrease the amount of disease in someone’s body more quickly. Chemotherapy varies significantly among different types of cancer, and also depending on many patient factors, and is too diverse to comment on in this podcast. But, one of the things I do want to point out – chemo is still rough and unpleasant, but the medications controlling nausea and vomiting, blood count issues, and more have come so far, and now many people continue on chemo for long periods of time living remarkably normal lives.
In metastatic disease, radiation is often used to fix local symptoms. We may use it to help with pain in a bony lesion, or shrink a lung mass that is bleeding or blocking things. Radiation is often the treatment of choice when dealing with spread to the brain, because the blood-brain barrier, which is a coating around our brains there to keep us from accidentally poisoning ourselves in trying out new berries in hunter-gather days, keeps out many of the targeted treatments and chemotherapy as well. Radiation may be given to the whole brain or just a few spots, again very dependent on the clinical picture, and not something that any hard and fast rule can be given here.
One of the things that is difficult for many patients with metastatic disease is understanding that they likely won’t be cured, and that they will be off and on treatment for the remainder of their time. Usually, patients will remain on a treatment until the cancer becomes resistant to it. We know the cancer has become resistant when we see it growing despite therapy either on physical exam, if it can be felt, or on imaging. When progression is found, then the medication is switched to a different medication, and the process begins again.
From an emotional standpoint, the diagnosis of metastatic disease is one of the hardest things for patients. The process of being on a medication, it failing, and moving to the next is overwhelming and hard for most patients, and can cause anxiety, depression and other challenges. If you are struggling with this, my prior podcast on PTSD may be helpful.
But, it can also be a time patients are grateful for. It gives you time to make a bucket list and check some of the things off of it. It gives people time to spend quality time with their loved ones, and say the things they really want to say. In the next few weeks, I will be doing a podcast with an amazing woman, Dr. Faryal Michaud, a palliative medicine doctor, and hear some of her thoughts on prioritizing in our lives – both when we are well and when our time may be more limited.
Finally, one thing I tell patients to at least consider when they are diagnosed with metastatic disease is to find out how much time they have, and then decide how they want to spend it. If someone’s time is short, often I suggest either short or long term disability, to allow them to spend more quality time with family and spending their energy on things they want to do, not on working. This may not be a good option for someone who has a very long expected survival, but I think it is still good to assess where you are, what you want to accomplish and experience, and plan accordingly!
Ok, my friends, I hope this wasn’t too tough this week. The take home messages: there are so many more things we can do no to both extend life and improve quality of life in people diagnosed with metastatic disease. Understanding your diagnosis and prognosis are key to making better decisions. Fear is normal, but may be overwhelming, in which case, you should ask for help. If you want to hear an amazing story of a long term survivor of breast cancer, listen to Joan’s story in podcast 32.
