Adjuvant Chemotherapy by Kevin Murphy, MDIntroductionAdjuvant chemotherapy is the use of drugs as additional treatment for patients with cancers that are thought to have spread outside their original sites. This type of treatment has been very successful in changing the behaviour of certain cancers such as breast cancer, testicular cancer, ovarian cancer, just to name a few. In order to understand how this type of therapy works and in some cases, doesn’t work it would be worthwhile to outline a few important points.First of all, one of the most confusing concepts for patients is visualizing how small cancer cells really are. When we reflect back on high school biology, we might remember what a cell looks like diagrammed on a textbook page; much, much larger than life. We might remember looking at onion cells under a microscope which magnified them so we could see how they were organized. But, it is very hard to understand the problem of cancer without first realizing how very, very tiny cancer cells are. Perhaps the best way to understand this is to reflect back to a religious question posed hundreds of years ago by very learned scholars. They pondered, if God were truly all powerful, and He could make angels, and make them very small; then, how many could dance on the head of a pin ? Needless to say, this question is still not resolved. However, it can be said with some certainty that cancer cells are not angels !! We can estimate that approximately one billion cancer cells would make up a lump with the diameter of one centimeter (about half an inch). If the head of a pin is about one millimeter (one tenth of one centimeter) in diameter then approximately one million cancer cells can make up a lump the size of the head of a pin. Visually we can look at the situation this way:FIG 1.Why is it important to focus on how small cancer cells are ? Because when a patient has been told by their surgeon….”we got it all”, then it is important to remember that cancer cells are quite capable of “hiding” out of sight from the surgeon’s view. Therefore, the expression “we got it all’ only applies to that cancer the surgeons are capable of seeing.Tests After SurgeryWhenever a patient is reviewed after an operation and advised to undergo various tests, there is an assumption that if the tests are negative, then there is no cancer present elsewhere. In reality, what the negative tests mean is that there is no detectable cancer present. Given the small size of cancer cells, it is quite possible that many cells are “hiding” out of view.Does this concept mean that cancers are never cured with surgery or radiation ? That everyone with cancer has tiny deposits lurking out of sight waiting to come back and strike a person down ? No. What we know is that some people are at risk of having cancer cells “hiding” out of sight. It is these people who may be suitable to receive adjuvant chemotherapy.What follows next is an explanation for adjuvant chemotherapy that is fairly consistent for any type of cancer. The exact details of treatment will change in terms of drugs dosages, side effects, etc. The general concepts will be the same.The Starting PointThe usual approach is to start after the patient has been “worked up”. This means that all the necessary tests designed to look for cancer elsewhere have been done and they are normal. As stated earlier, this just means that the tests can’t find any cancer. It still may be lurking around somewhere else in the patient’s body. Are there different amounts for each patient? Yes. Are all patients at the same “starting point” ? The answer is No. Everybody is different.Fig 2.In the above diagram, the Y (vertical) axis represents the number of cancer cells that can develop with continued growth of a cancer. The two horizontal lines represent the number of cancer cells that can be found by a physical exam (visible by exam) and the next one down represents the number of cancer cells that be found by tests , such as bone scans, CT scan, X rays,etc (visible by tests). Any number of cancer cells below the test line is undetectable (invisible).From the above diagram you can see two round circles, A and B. A represents the number of cancer cells that are present in patient A and B represents the number of cancer cells in patient B. Both patients have surgery which removes all visibly detectable cancer. For example patient A had a large lump in her right breast measuring 4-5 cm in diameter. Patient B had a smaller lump about 1-2 cm in diameter removed from her left breast. After the surgery both patients were investigated with various tests to see if any residual cancer could be detected. None was. If you look at the circles labelled A and B after surgery you can see that patient A has a larger amount of cancer cells left over than patient B. Both amounts , however, are still below the “test line” and therefore are not detectable (“invisible”). Both patients are eligible for additional treatment such as adjuvant chemotherapy. They may have the same treatment which can kill many millions of cancer cells. The chance of cure, however, will be better for patient B since the number of her residual cancer cells is less than patient A.Although generally speaking, the larger the cancer at diagnosis, the greater the chance of more cancer cells left behind (patient A’s cancer), this relationship is not always true. Some patients have cancers that do not develop the ability to migrate elsewhere (metastasize). These can become large and inactive. Other patients have cancers that develop the migrating ability early in their growth before they can be found on examination or even screening. These migrating cells can grow enough to prevent additional treatment from being useful.The TreatmentOnce the treatment has been started, it is usually impossible to tell whether it is working. This is because we are dealing with very small cells that are scattered around the body, too small in number to find and hiding in relatively large organs. What is usually done is to check periodically that the cancer has not “broken through” the treatment. We know that certain lab tests are better at finding cancer than a physical examination. Therefore, on a regular basis, a few tests can be done to check the situation. This may mean only blood tests, or perhaps an X ray.Fig 3.The above diagram is similar to the one above (Fig. 2). It differs however, in that it is designed to show what can happen during adjuvant treatment. The round circles represent the number of residual cancer cells for three patients. For example, patient A has residual cells left behind after surgery and they are sensitive (S) to the treatment (they can be killed). Therefore, with 6 cycles of treatment patient A is cured. Patient B has some cancer cells which are sensitive to treatment and are killed during the early period of therapy. Some of the cells, however, are resistant (R) to treatment (cannot be killed) and they become the majority of the cancer cell population. This population then grows undetected until it can be found by lab tests, and then by examination. Patient C has resistant cancer from the very beginning. By doing checks with each treatment it becomes very clear that by treatment 5 the cancer is growing and further treatment for patient C is of no value.Follow Up (After Treatment)Once treatment has been completed, many patients ask what “check ups” will be done to ensure that the cancer hasn’t come back. This brings up a difficult problem. As discussed earlier, the use of tests to find very small amounts of cancer cells is limited by the ability of the tests. Therefore, a negative test does not mean the absence of cancer cells. It just means the test is negative. In addition, if a test is positive, and is accurate at detecting cancer as a cause for the positive test, then what is next? If a test shows the presence of cancer deposits in an organ like the liver, what treatment do we have to get rid of the cancer ?If adjuvant chemotherapy is used to destroy “left over” cancer cells, then we would use the best possible drugs to do the job. In other words, send in the “A team”, to borrow an expression from the sports world. If this treatment is not successful, then we can expect that the cancer cells still alive after the initial treatment will be resistant to the first line drugs (the A team). This usually implies that the cancer cells will be resistant in part to second line drugs (the B team). Therefore, there is very little chance that further treatment will provide a cure. This is particularly true for patients with the common cancers such as breast, lung, bowel and prostate cancer. Some less common cancers can be cured after they come back with very aggressive treatment which may include bone marrow transplantation.Given the current therapy available, it makes more sense to follow patients using clinical methods (a thorough history and physical) rather than using tests. If a patient develops symptoms that are related to recurrent cancer, then treatment can be directed towards helping the patient feel better. If a patient has cancer that has recurred but is feeling well, then there is no treatment which will help the patient feel better. Rather, the treatment, with its side effects, may make the patient feel worse.Editor’s Note: Dr. Murphy makes a lucid argument here, but there are also other points of view. In the US, at least, it is common for patients to receive more aggressive follow-up than what Dr. Murphy describes here. As in many areas of medicine, not everyone has the same philosophy. Similarly, oncologists and patients may have different philosophies and strategies for dealing with recurrent cancer, and, of course, it depends greatly on the individual situation, and on the patient’s wishes. – Steve DunnMany patients, after adjuvant therapy, feel unsure of what to look for in the way of symptoms. Since they are actually healthy people it is helpful to realize that all the usual colds, flus, aches and pains will affect them just like anybody else. If their cancer is to return and cause problems, then the problems that need treatment will be symptoms that just don’t go away, like the common cold, the flu, or the usual aches and pains from everyday life.SummaryAdjuvant chemotherapy for cancer is a difficult treatment to understand. As one patient said: ” You are suggesting that I have treatment which will make me temporarily unwell, to treat cancer that you can’t find, and can’t be sure you have eliminated even when treatment is finished”. That is what adjuvant treatment is about. It is similar to life insurance. When you pay your premiums to the insurance company, you are recognizing a potential risk to your life that may or may not happen (car crash, sickness, earthquake, hurricane, etc.). Treatment with adjuvant chemotherapy is designed to reduce the risk of cancer returning. Large scale clinical trials have shown significant benefit from adjuvant therapy for patients with breast cancer, colon cancer, testicular cancer, lymphomas, etc. However, like so many things in life, adjuvant therapy does not come with a written guarantee. In spite of this “no guarantee” clause; when the length of time on treatment along with its side effects are balanced with the possible benefits such as a longer life, then for most patients eligible for treatment the benefits usually outweigh the risks.
July 28, 2019 0 Comments