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Facing the unknown
Many oncologists, like myself, feel a tremendous emotional burden when they have to convey to another human being that they have an incurable illness (never could I have imagined earlier in my life that I would regularly have to do this). This discussion is made all the more stressful when a patient insists on knowing how long he or she will survive. The reason that this is so difficult to address is that no oncologist can predict the course of a patient's cancer or how it will respond to treatment. Certainly, an average survival estimate can be provided for any cancer. Yet such a number is drawn from an analysis of groups of patients and must be qualified by the recognition that every patient is unique and reacts uniquely to cancer treatments. Patients whose cancers respond to treatment survive longer than those whose cancers fail to respond. But how a cancer will respond to treatment cannot be known before those treatments are administered.
Furthermore, at the quickening pace of drug development today, it is possible that a promising new drug may come along that extends the lives of patients with a particular cancer. For example, in the past few years alone, several new drugs have been approved for the treatment of colon cancer, such as irinotecan (Camptosar), oxaliplatin (Eloxatin), capecitabine (Xeloda), bevacizumab (Avastin), cetuximab (Erbitux), and panitumomab (Vectibix), after decades of having just one drug (5-FU) to treat the disease. In addition, innovative combinations of new drugs with older ones are being introduced yearly, with each new combination extending life even further.
For these reasons, prognosis is not easy to predict accurately and often takes time to determine. The factors that oncologists use to try to estimate prognosis are discussed next.
The five elements of prognosis
Five elements go into determining the behavior and survivability of a cancer. The first four are readily known, whereas the fifth is more difficult to ascertain and is of my creation (drawn from the scientific work of many others). The five prognostic elements are:
1. The type and grade of cancer
2. The stage of cancer
3. The general health of the patient
4. The prognostic factors" of the cancer or patient
5. The biological essence of the cancer
The cancer type, grade, and stage (elements 1 and 2) go hand in hand in determining prognosis. As discussed earlier, these two elements are by far the most important in determining prognosis. A person's general health (element 3) determines how well he or she can tolerate the recommended treatments. For example, someone with an aggressive cancer who also has severe heart problems would have a difficult time tolerating strong chemotherapy or extensive surgery. The chemotherapy doses would likely have to be lowered, and the surgery would have to be limited; these facts would diminish the chances that this person could beat the cancer. In fact, some very infirm individuals may face a greater risk of dying from other medical conditions than from their cancer; it may be in their best interest not to treat the cancer in such a situation. Age is a consideration in determining prognosis because the older the person, the harder it is for their bodies to withstand strong anticancer treatments. On the other hand, a seventy-year-old man in perfect physical condition may tolerate cancer treatments better than a forty-year-old man who has abused his body and health, so age itself is not blindly used to guide treatment recommendations.
A prognostic factor (element 4) represents some medical or scientific aspect of the cancer or the patient that aids in estimating prognosis. For example, a patient who has breast cancer that has spread to axillary lymph nodes would have a certain estimated prognosis based on the stage (TNM designation) of the cancer. Beyond determining the size of the primary tumor (T) and number of affected lymph nodes (N), pathologists will analyze a breast cancer specimen for the presence of a protein called Her2/neu, or Her2" for short. If Her2 is found on the surface of the cells, the breast cancer would be further categorized as Her2 positive." Her2's function in the cell is to stimulate the growth of the cancer: among patients with the same stage of breast cancer, those who are Her2 positive would be predicted to have a poorer prognosis than those who are Her2 negative. Fortunately, however, an anticancer drug that specifically blocks the function of Her2, called Herceptin, has greatly improved the survival of Her2 positive breast cancer patients.
Two other prognostic factors used in breast cancer are the estrogen receptor and progesterone receptor. The estrogen and progesterone receptors are proteins found in normal breast tissue, as well as in many breast cancers, that bind to the hormones estrogen and progesterone, respectively. Breast cancers that make these estrogen and progesterone receptors are generally less aggressive and have a better prognosis than those that do not.
Blood tumor markers that relate to cancer growth are associated with numerous cancers, and sometimes they have prognostic importance. For example, among men diagnosed with prostate cancer, the higher the PSA at diagnosis, the lower the chances for cure; in testicular cancer, the higher the blood levels of AFP (alphafetoprotein) and HCG (human chorionic gonadotropin), the more difficult it is to cure.
Combining prognostic factors
Some cancers have prognostic models," scoring systems," or nomograms" in which several aspects of the cancer and patient are combined to determine the chances that the disease will return (relapse) after initial therapy. Some of the more commonly used models are for prostate cancer, kidney cancer (Memorial Sloan-Kettering Cancer Center, or MSKCC, criteria), non-Hodgkin's lymphoma (International Prognostic Index, for diffuse large cell and follicular types), and multiple myeloma (International Scoring System).
Perhaps the most advanced and widely used prognostic tool has been developed for early-stage (stages I–III) cancers of the breast, colon, and lung. This tool is a computerized program called Adjuvant! Online, in which the oncologist enters clinical information about the patient (age and overall health) and cancer (tumor size, grade, and number of lymph nodes involved) and obtains a risk profile of that cancer. The oncologist can then choose a treatment option (such as a particular chemotherapy regimen) and the program will estimate the benefit of that treatment for the patient; the benefit relates to the reduction in the risk or chance that the cancer will return and the survival in years gained from the therapy. The results can be printed in a patient-friendly graphical format, which the oncologist can share with the patient.
The main reason oncologists want to know the risk profile or aggressiveness of a cancer is to guide treatment decisions. If a cancer is deemed to have aggressive features, then stronger treatments would be recommended to try to eradicate it and prevent it from returning; if it has less aggressive features, then strong treatments would not be necessary. This explains why cancer researchers and practitioners are so focused on identifying the behavior of a cancer before a patient starts treatment. No one wants to subject someone to strong therapies with powerful side effects if they are not truly indicated. If we can identify which cancers need strong therapies and which can be successfully treated with milder therapies, then each patient will receive the optimal and necessary treatment for his or her cancer. This is a central goal of the field of cancer medicine.