About Author:
Dr. Vishwas B. Chavan
Ph.D. (Biochemistry)
Andheri (East), Mumbai – 400069
vishwaschavan2003@yahoo.co.in
Abstract:
The word “Cancer” is still synonymous with death for common people and the “stage IV cancer”, which is typically known as “last stage cancer”, is loss of hope even for medical community.
Many times patient presents to clinic, when cancer had already crossed IInd or IIIrd stage. This is mostly due to the reason that cancer may not have any symptoms at initial stages. Even if there are any symptoms, they can be mild and vague. Further rising cost of healthcare forced many patients, particularly women, to delay approach to physician. Therefore it is not uncommon for cancer patients to hear sentences like, “You are too late”, “You should have come earlier” etc. which is more depressing. This is a humble attempt to give the these patients some ray of hope.
So, in this 21st Century, is it necessary, that cancer should be equal to death all the times, even when it has reached stage IV? To get answer of this question, we need to first know what stage IV cancer is and what its effects on human body are.
As most people know, cancer or malignancy means uncontrolled growth of any cell of the body. The mechanism which controls the growth of cells is lost in malignant cells. Cancer can occur in any cell of body and hence any organ can be affected by cancer, though cancers of some organs are more prevalent in some populations.
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Staging of cancer:
After the diagnosis of cancer is confirmed, the next important thing is to determine the stage of cancer. This is because cancer stage at the time of diagnosis is the main predictor of survival and also determined the treatment options. Also, even though cancer type is same for many patients, treatment differs significantly according to cancer stage. This means the patient who has stage I cancer will require different treatment than who has stage IV cancer of the same type. In simple terms, the stage of cancer describes how much cancer has been spread in the patient’s body, i.e. severity of cancer. Therefore the stage of cancer depends on the size of primary tumor, it’s penetration in original site/organ, invasion of other organs, both adjacent or distant (metastasis) and number of lymph nodes affected.
Generally, the stage of cancer is denoted by numbers 0 to IV.
- Stage 0:Cancer in situ (confined in original organ).
- Stage I: Cancer is localized to one part of the body.
- Stage II: Cancer is locally advanced.
- Stage III: Cancer is locally advanced and some lymph nodes are affected.
- Stage IV: Cancer has been metastasized, i.e. cancer has been spread to other organs or throughout the body.
However, it should be remembered that criteria for stages differ for different types of cancers.
Cancer staging may also be divided into a clinical stage (based on physical and imaging studies like X-ray, endoscopy etc.) and pathological stage (based on examination of tumor cells under microscope). In TNM (Tumor, Node, Metastasis) staging system, clinical and pathological stages are denoted by small “p” or “c”. For example, T3N2M0 denotes a large tumor (T3), which has spread to nearby lymph nodes (N2), but not to other parts of the body (M0, no metastasis). This staging system is used for most cancers except brain tumors and blood cancers. Clinical stage and pathological stage are often different; however, they should complement each other to give complete picture of patient’s cancer to the oncologist.
Generally, cancer is not life-threatening in primary stage, but it is when it spreads to other parts of the body (metastasis).The tumor cells detaches from main tumor and reaches to distant organs through blood stream or lymphatic system. Generally, cancer spreads to other organs by following routes:
- By direct extension to adjacent organs.
- Through lymphatic vessels to regional lymph nodes.
- Tumor can invade a blood vessel and then tumor cells can break free from main tumor and spread to other organs via blood.
- By spreading through serous cavities, after growing through the wall of an organ.
Often individual tumors use more than one mode of spreading.
EFFECT OF STAGE IV CANCER ON HUMAN BODY
The hallmark of stage IV cancer of any type is metastasis (spread of cancer cells to distant organs or throughout the body). This happens when tumor cells separates from primary tumor, carried away by blood or lymph, settle on any distant organ/tissue, penetrate the cell barrier and then multiply forming another tumor (secondary or metastatic tumor). When a new tumor is formed in the adjacent tissue/organ, it is called local metastasis. Common sites of metastasis are lungs, bones, liver and brain. Though located in different organs, the tumor cells retain their original characteristics. Thus, if breast cancer metastasized in lungs, the tumor in lungs is formed of breast cancer cells and called metastatic breast cancer and not lung cancer. (en-wikipedia.org/wiki/metastasis)
Certain tumors metastasize preferably in particular organs. e.g. prostate cancer generally metastasized in bones, colon cancer metastasized in liver etc. According to theory, cancer cells metastasized to organs where they got similar environment. For example, breast cancer cells often metastasized to bones, because in each organ, they can get calcium ions (milk in breast and calcium in bones).
Symptoms: The symptoms of cancer metastasis depend on the location of tumors. Generally, lymph nodes near the primary tumor are first affected by metastasis and lymphadenopathy is common symptoms. Metastasis in lungs causes shortness of breath and hemoptysis (coughing of blood) while metastasis in liver causes jaundice and hepatomegaly (enlarged liver).Bone metastasis causes bone pain and frequent fractures. Metastasis in brain causes headaches, vertigo and seizures.
DEALING WITH STAGE IV CANCER
Problems in dealing with stage IV cancer: Most of stage IV cancer treatments currently available are of type of palliative care. They are not of curative, but help the patient to live longer, with less pain. Stage IV cancer can’t be completely removed by surgery; hence chemotherapy becomes the frontline treatment. However, surgery can be used to relive some symptoms liker obstruction.
Importance of chemotherapy in stage IV cancer: Chemotherapy is the primary treatment for stage 4 cancer and generally extends life and frequently alleviate cancer-related symptoms. In stage 4 cancer treatment, chemotherapy is used to kill the disseminated cancer cells. There are reports of partial response, reduction of at least 50% of the tumor in response to chemotherapy. Multimodal therapy is generally provides more response than a single chemotherapeutic agent and lower the possibility of drug resistance.
Meta?analyses have shown that chemotherapy produces modest benefits in short?term survival compared to supportive care alone in patients with inoperable stages IIIb and IV disease (www.nci.net). This means chemotherapy of stage IV cancer generally extend the life of the patient than a person who receives only supportive care.
There is significant evidence that chemotherapy also improves quality of life. Disease-related symptoms will improve after chemotherapy, sometimes even in the absence of a measurable tumor response.
Chemotherapy Side Effects: Since chemotherapy attacks rapidly dividing cells, it can also attack rapidly dividing healthy cells like hair follicles, bone marrow and the stomach-lining, leading to side effects such as hair loss, digestive problems, nausea, mouth sores and lowered blood-cell counts. However, it should be noted that chemotherapy side effects vary from person to person.
A cycle of chemotherapy for stage IV cancer may involve 4-6 months of time and different combinations of anticancer drugs, which can be given orally or intravenously. There are more than 200 chemotherapy medicines which are used in at least 50 combinations. Sometimes, however, many types of tumors develop resistance to chemotherapy. In these cases, oncologists may try a different chemotherapy combinations or radiotherapy. Also, enrolling in a clinical trial exploring a new treatment option or a new combination of existing treatment options can be a promising option.
Radiation therapy, though not fully curative, can also be used to provide some relief from symptoms.
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Treatment of blood cancers and brain tumors
Leukemia:Patients with Stage 4 chronic lymphocytic leukemia (CLL), is treated with chemotherapy, surgical removal of the spleen, radiation therapy, biological therapy, bone marrow transplantation, and peripheral stem cell transplantation.
Brain Cancer: The stage 4 brain cancer is treated with one or a combination of the following: Chemotherapy, Radiation Therapy, Biological Therapy, Surgery, Hormone Therapy, Cryosurgery.
Dealing with stage IV cancer patients
This is very critical step because for a given cancer, there are different types with different areas of metastasis. Further, other comorbidities like diabetes mellitus and overall performance status of the patient play important role in survival. For example, a younger patient with less metastasis have increased chance of survival than an older patient with diabetes and/or multiple metastases. Similarly, an ambulatory patient able to do his daily activities has a high performance status, and better survival rate than a bed-ridden patient. Three studies that have included large numbers of patients with cancer at all stages found that functional or performance status was the accurate predictor of survival. Decline in activities of daily living including bathing, continence, dressing and transfer, were very strongly associated with decreased survival. On the other hand ability to perform most of the activities of life generally shows no immediate danger.
Most of stage IV cancer patients have undergone numerous therapies (surgery, chemotherapy or radiotherapy). All these treatments have serious side effects and therefore caused considerable damage to normal cells, including those of immune system, which normally keep check on abnormal cells (which can become cancerous). It was also found that cancer patients have very low total antioxidant capacity compared to age-matched controls (200.1µM Vs. 914.1µM). [T. Angeline et al 2006, 33rd ACBICON].
Research is showing that different patients respond differently to same treatment based upon subtype of their cancer and genetic profile of their body. Hence nowadays, oncologists are tailoring treatments according to individual patient.
Survival rate: Cancer survival rates vary for stage 4 patients. The reason for this is that patients have different areas of metastases, cancer subtypes, age, sex, general health, treatment available, will power of patient, performance status, and genetic makeup. All these factors makes prediction difficult.
The survival rate is generally expressed as life expectancy in the next 1 to 5 years. Generally young patients and women can exceed their average survival rates (www.buzzle.com/articles).
Rays of hope
78 % patients with stage IV choriocarcinoma can have complete or prolonged remission with multimodality therapy. One case of an aggressive choriocarcinoma with multiple metastases to the brain and visceral organs was reported recently. The cancer was so aggressive that the patient had radiological evidence of new lesions occurring almost every week while on the initial treatment and yet had a complete long term remission with surgery and EMA-CO chemotherapy (Journal of Cancer Research and Therapeutics; Oct – Dec 2010; 6(4): 552 – 556). Another success story was reported with stage IV non-small cell lung cancer (West Indian Medical J. 2012, Jan 61(1):106-108).
Controlling metastasis: For metastasis, new network of blood vessels should be formed (tumor angiogenesis). Therefore angiogenesis inhibitors can prevent metastasis. Bevacizumab is commonly used for metastatic colon cancer, which prevents the growth of new blood vessels. Because metastases need to develop new blood vessels in order to survive, this can slow the spread of colon cancer to other areas of the body.
Endothelial progenitor cells are essential for metastasis. Inhibition of these cells in the bone marrow leads to significant decrease in tumor growth and angiogenesis. Body resists metastasis by actions of some proteins called as “metastatic suppressors”.
If the metastases cannot be surgically removed, chemotherapy drugs can be administered directly into the hepatic artery (a large artery in the liver) which can shrink the tumor and can allow treatment via cryosurgery (freezing the metastases), or radioablation, which uses a short concentrated burst of radiation to kill the metastatic cancer.
Also, vascular growth factor and its receptor are associated with cancer metastatic behavior. These factors can be tested and results can be considered in planning treatment.
Gene therapy: In this, a drug targets a specific gene involved in a particular cancer. If the particular growth factor required by cancer cells can be identified or faulty signaling by normal cells is stopped by targeting a particular gene, the adverse side effects of the drug can be minimized, targeting only cancer cells and sparing normal cells.
Following strategy can be employed to get maximum response to treatment:
1. Identify the exact subtype of cancer and growth factors affecting tumor growth.
2. Determine patient’s genetic profile.Prescribe drugs according to particular genetic characteristics of tumor, tumor growth factors and patient’s genetics. This may include suppressors of tumor growth factors or activators of patient’s immune system against tumor. For example, in Stage IV breast cancer, if the cancer is hormone receptive, estrogen blockers can be used to slow or stop the growth and spread of cancer. Some drugs which blocks the supply of blood to the cancer cells can be used for some types of cancers.
3. Patient can also participate in a clinical trial which is studying a new drug or new combination of current drugs.
4. Positive mental attitude can play a role and that the willingness to fight and undergo treatment can extend life. Patient should be encouraged to do his/her daily activities, because an ability to perform most of the activities of life generally shows no immediate danger.
5. Joining cancer support groups is also helpful in maintaining will power of the patient Patient’s moral can be boosted by hearing cancer survival stories.
At last, is here is one noteworthy example of combat to stage IV cancer. At the young age of 13, Sean Swarner was diagnosed with advanced stage 4 Hodgkin’s Lymphoma, a type of cancer. After tough treatments like chemotherapy and radiation, he went into remission. Again, at the age of 15, Sean was diagnosed with Askins Carcinoma, which has a 6% survival rate and Sean was given 14 days to live. The treatments were so harsh that he was put in a medical induced coma for 1 year, because doctors were afraid the treatments would kill him before the cancer could. Again he survived and went on to do things that require great courage, like climbing Mt. Everest.
And that’s why the title: Stage IV cancer: Battle not lost yet !.......
References:
1. ehow.com/about_5063356_treatments-prostate-cancer-stage.html
2. stage-4-prostate.cancertreatment.net
3. ehow.com/way_5130375_treatment-stage-iv-lung-cancer.html
4. (lungcancerbookandnewsletter.com/
Stage%204%20lung%20cancer%20treatment%20revised.htm)
5. (leukemialymphomatreatmentfyi.com/leukemia_treatment.html)
6. (buzzle.com/articles/stage-4-brain-cancer.html)
7. (ehow.com/way_5130375_treatment-stage-iv-lung-cancer.html)
8. (ehow.com/about_5063356_treatments-prostate-cancer-stage.html)
9. (stage-4-prostate.cancertreatment.net)
10. (leukemialymphomatreatmentfyi.com/leukemia_treatment.html)
11. (buzzle.com/articles/stage-4-brain-cancer.html)
12. (ehow.com/about_5085681_colon-cancer-stage-iv-treatment.html)
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