What is Kidney Cancer?

Kidney cancer is a malignant, uncontrolled cell proliferation and growth that originates from kidney cells. Renal cell carcinoma (RCC), also known as renal cell cancer or renal cell adenocarcinoma, is the most common type of kidney cancer. About 9 out of 10 kidney cancers are renal cell carcinoma. Less commonly, some types of kidney cancer, which we will talk about below, may occur. Young children are more likely to develop a type of kidney cancer called Wilms’ tumor. Although kidney cancers are usually seen as a single tumor in the kidney, they can sometimes develop in more than one focus in one kidney or even in both kidneys at the same time.

There are several subtypes of kidney cancers according to the cell type they contain. Knowing the subtype of cancer can be a factor in deciding on treatment and can also help determine whether the cancer is caused by an inherited genetic syndrome. Kidney cancers account for about 2% of all cancers seen in the body. Kidney cancers are seen 2-3 times more frequently in men than in women, and they occur mostly in the 60-70 age group.

Classification of Kidney Cancers

1-Clear cell renal cell carcinoma: It is the most common subtype of renal cell cancers, accounting for approximately ⅔ of kidney cancers (70-75%). When seen in the lab, the cells that make up clear cell cancer appear very pale or clear.

2-Papillary renal cell carcinoma: It is the second most common subtype of kidney cancers – approximately 10-14% of these subtypes. Also known as chromophilic cancers. These cancers form little finger-like projections (called papillae) in some, if not most, of the tumours. Some doctors call these cancers chromophilic because the cells are stained with certain dyes and appear pink when viewed under the microscope. These are further subdivided into type 1 and type 2.

3-Chromophobe renal cell carcinoma: This subtype accounts for about 5% of all kidney cancers. The cells of these cancers, like clear cells, are pale, but much larger and have other characteristics when viewed very closely under the microscope.

4-Rare types of renal cell cancer: These subtypes are very rare and each account for less than 1% of kidney cancers: Collecting duct cancer, Multilocular cystic kidney cancer, Medullary carcinoma, Mucinous tubular and spindle cell carcinoma, Neuroblastoma-associated renal cell cancer. These are quite malignant and have a bad course.

5-Unclassified renal cell carcinoma:Although it is very rare, it is called unclassified because there is more than one type of cancer cell that does not fit into any of the other categories.

6-Types of non-renal cell kidney cancer:Other types of kidney cancer include transitional epithelial cell (Urothelial) carcinomas, Wilms tumors, and renal sarcomas.

Transitional epithelial cell carcinoma: 5-10% of kidney cancers are transitional epithelial cell carcinomas, also known as urothelial carcinomas. These are not real kidney cancers, but cancers that originate from the kidney pool (pelvis) and ureter (kidney canal) and are treated like bladder cancer. Pelvis renalis and ureter tumors will be examined under another topic.

Wilms tumor (nephroblastoma): Wilms tumors almost always occur in children. This type of cancer is very rare among adults. This type of cancer is described more broadly under the title of childhood tumors.

Renal sarcoma: Renal sarcomas are a rare type of kidney cancer that starts in the blood vessels or connective tissue of the kidney. They make up less than 1% of all kidney cancers.

Benign (non-cancerous) kidney tumors

Some kidney tumors are benign (not cancerous). This means that they do not metastasize (spread) to other parts of the body, but can still grow and cause problems. Treatments that are also used for kidney cancers such as benign kidney tumors, surgery or radiofrequency ablation may be used. The choice of treatment depends on many factors, including the size of the tumor and, if it is causing any symptoms, the number of tumors, whether the tumors are in both kidneys, and the person’s general health.

2-Angiomyolipoma: Angiomyolipomas are the most common benign kidney tumor. They are more common in women. It can develop sporadically or in people with tuberous sclerosis, a genetic condition that also affects the heart, eyes, brain, lungs, and skin. These tumors are made up of different types of connective tissues (blood vessels, smooth muscle, and fat). If they do not cause any symptoms, they can usually be watched closely. If they start to cause problems (such as pain or bleeding), they may need to be treated.

2-Oncocytoma: Oncocytomas are benign kidney tumors that are uncommon and can sometimes grow quite large. They are more common in men and do not normally spread to other organs, so surgery usually cures them. Although rare, they can become cancerous.

Causes and risk factors of kidney cancer

Some of the kidney cancers have genetic and hereditary (familial characteristics). (for example, a deletion in the p arm of the 3rd chromosome) causes cells to grow and divide rapidly. Some cells may metastasize and spread to distant parts of the body. A risk factor is anything that increases your chances of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, such as smoking Factors such as your age or family history and genetics cannot be changed.There are some modifiable and non-modifiable risk factors for kidney cancers.

These:

1-Aging:Your risk of kidney cancer increases as you get older.

2-Cigarette: Smokers have a higher risk of kidney cancer than non-smokers. This relative risk decreases after quitting smoking.

3-Obesity and malnutrition:Obese people have a higher risk of kidney cancer than people who are considered to be of a healthy weight.

4-High blood pressure (hypertension):High blood pressure increases your risk of kidney cancer.

5-Treatment of kidney failure:People who take long-term dialysis to treat chronic kidney failure have a higher risk of developing kidney cancer.

6-Workplace Risks:Many studies have suggested that workplace exposure to certain substances, such as trichlorethylene, increases the risk of kidney cancer.

7-Race and breed:It is more common in black race and kidney cancer is seen 2-3 times more in men than in women.

8-Some inherited genetic syndromes:People born with certain inherited syndromes may have an increased risk of kidney cancer, such as those with von Hippel-Lindau disease (VHL gene-3p deletion), Birt-Hogg-Dube syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, or familial kidney cancer.

9-Family history of kidney cancer. YThe risk of kidney cancer is higher if flock family members have had the disease.

Can we prevent kidney cancer?

Setting aside unmodifiable risk factors such as genetic and familial predisposition, race, and ageing, here are some suggestions that may help reduce your risk of developing kidney cancer:

1-You should not use cigarettes and tobacco products: If you smoke, quit. Many quitting options are available, including support programs, medications, and nicotine replacement products. Tell your doctor you want to quit and discuss your options together.

2- Fight against obesity: Maintain your healthy weight. Try to maintain a healthy weight. If you are overweight or obese, reduce the number of calories you consume each day and try to be physically active most days of the week.

3-Blood Pressure Control: Control high blood pressure. If you have high blood pressure, you can discuss options for lowering your numbers. Lifestyle measures such as exercise, weight loss, and dietary changes can help. Some patients may need medication to lower blood pressure.

4-Occupational exposure:Avoiding exposure to harmful substances such as trichlorethylene at work can also reduce your risk of kidney cell cancer.

Kidney cancer symptoms

Early kidney cancers usually do not cause any signs or symptoms, but kidney tumors that reach larger volumes may give some signs and cause some complaints. These signs and symptoms may be caused by another type of cancer other than kidney cancer, or by other diseases of the kidneys and urinary tract. For example; Bleeding in the urine may also be due to a bladder or urinary tract infection or kidney stone. However, if you have any of these signs, it is recommended that you see a doctor.

Some possible signs and symptoms of kidney cancer include:

  • blood in the urine (hematuria)

  • Flank pain-flank pain (pain in the kidney area)

  • Palpable mass-swelling (lump) in the lower back or abdomen

  • Fatigue-fatigue

  • Loss of appetite

  • Non-diet weight loss

  • Fever that is not caused by infection and does not go away

  • Anemia-Anemia

  • Some people may also experience a condition called paraneoplastic syndrome (fever, anemia, hypertension, loss of muscle mass, weight loss, fever, changes in liver enzymes and platelets).

  • Bone pain or a persistent cough may indicate that the cancer has spread to other parts of the body.

DIAGNOSIS

About two-thirds (⅔) of kidney cancers are diagnosed early as being very limited to the kidney, while 1/3 come in a state that has spread and metastasized. In addition to the patient’s history and physical examination, a number of imaging methods (for both diagnosis and metastasis research) are used for diagnosis.

Medical history and physical examination: If you have any signs or symptoms that suggest you may have kidney cancer, your doctor will question your entire medical history to check for risk factors and learn more about your symptoms. On physical examination, an abnormal mass (lump) may be felt when examining your abdomen (belly). If symptoms or the results of a physical exam show that you may have kidney cancer, further testing will be done. These usually include laboratory tests, imaging tests or kidney biopsies.

Blood tests: Lab tests often can’t definitively show whether kidney cancer is present, but they can provide the first clue that a kidney problem may be present and are done to help understand a person’s general health and whether the cancer has spread to other areas. Complete blood count is usually abnormal in people with kidney cancer and anemia due to bleeding is more common. Less frequently, a person may also have an excess of blood (called polycythemia) because kidney cancer cells produce a hormone (erythropoietin) that causes the bone marrow to make more red blood cells. In other blood tests, liver enzymes may be elevated due to neoplastic syndrome, and tests such as blood calcium measurement and urea creatinine, which shows kidney function, are definitely required.

Urine test: Microscopic bleeding, invisible to the naked eye, may be detected in the urine. About half of all patients with renal cell cancer have blood cells in their urine. If the patient has cancer of the transitional epithelium (in the renal pelvis, ureter or bladder), true cancer cells in the urine can be detected by pathological examination of the urine sample by a special test (called urine cytology).

Computed tomography (CT) scan: A CT scan is requested to obtain detailed cross-sectional images of your body. It can provide precise information about the size, shape, and location of a tumor. It is also useful in checking whether a cancer has spread to nearby lymph nodes or to organs and tissues other than the kidney. If a kidney biopsy is needed, a CT-guided biopsy can be performed from the mass to diagnose cancer.

Magnetic resonance imaging (MRI) scan: In kidney cancer, if tomography cannot be performed due to allergy or to examine the tomography findings in more detail, it is recommended. It is also used to determine the stage of cancer and to investigate metastases.

Ultrasound: Ultrasonography is one of the basic tools used in the diagnosis of kidney cancer. Many cases are detected during routine ultrasound examinations without any symptoms. The mass seen in the kidney indicates whether it is cystic or solid (kidney tumors are more likely to be solid-solid). Different ultrasound models can also help him tell the difference between some types of benign and malignant kidney tumors.

Angiography: Angiography is an X-ray test that shows the kidney blood vessels. This test can help plan surgery for some patients. Currently, angiography is done as part of a CT or MRI scan rather than a separate X-ray test.

Chest X-ray: After kidney cancer is diagnosed, an X-ray may be taken to see if the cancer has spread to the lungs. More often, chest CT can be done because it can see abnormal areas better.

Bone scan: A bone scan can help show if a cancer has spread to your bones. A small amount of low-level radioactive material is injected into the blood and is collected mainly in areas of abnormal bone. It may be done if there is a reason to think the cancer may have spread to the bones, such as bone pain or blood test results that show an increased calcium level.

Kidney biopsy: Unlike most other types of cancer, biopsies are not often needed to diagnose kidney tumors. Imaging methods can provide sufficient information for surgery. Definitive diagnosis, stage and grading are determined in the pathological examination of the removed part after surgery. However, if the information obtained by imaging methods is suspicious or insufficient for the diagnosis of kidney cancer, a small tissue sample can be taken from the region where it is thought to be cancer. Or, in cases where kidney cancer is thought to have spread to other areas, a biopsy may be performed from the metastatic site instead of the kidney. or small tumors for which surgery and treatment are not considered, or when other minimally invasive (radiofrequency and cryotherapy) treatments are considered, a biopsy may also be performed to confirm cancer. There are 2 types of kidney biopsy that can be preferred: fine needle aspiration (FNAB) and needle-core biopsy. Depending on the condition of the mass, it is decided which type of biopsy method will be used. It is performed under local anesthesia and under the guidance of tomography or ultrasound.

Rating System: It is the evaluation of how aggressive the tumor cells are in the pathological examination of the biopsy or surgical material. The most commonly used system to determine this is the Fuhrman rating system. According to the character of the cancer cells, the pathologist grades the cancer from 1 to 4 (Fuhrman being the best-4 being the worst).

Staging of Kidney Cancers

After diagnosing kidney cancer, it is necessary to look at whether the disease has spread and, if so, how far it has spread. This process is called staging, and the stage of cancer is a classification of how far it has spread throughout the body. It helps to determine the protocol about how the cancer will be treated. This cancer stage is also used when talking about how the cancer will progress, and the patient’s survival statistics. Stages of kidney cancer range from I (1) to IV (4). As a rule, the lower the number, the less the cancer has spread. Stage IV means that the cancer has spread more. The most commonly used staging system for kidney cancer is the American Joint Committee on Cancer (AJCC) TNM system.

The TNM system is based on 3 basic information:

  • 1-Size and size of the main tumor (T): How big is the tumor? how much has it grown towards neighboring areas?

  • 2-Spread to nearby lymph nodes (N):Has the cancer spread to adjacent lymph nodes?

  • 3-Spreading to distant regions (metastasis) (M):Has the cancer spread to other organs such as the bones, brain or lungs?

Kidney cancer is clinically staged according to the results of physical examination, biopsy and imaging tests, and if the results of the pathological examination after surgery are included in the staging, this is also called the pathological stage or surgical stage.

According to this, staging of kidney cancer:

T- Tumor size

T1:Tumor <7 cm or less in greatest dimension, confined to the kidney

T1a:Tumor <4 cm or less

T1b:Tumor > 4 cm, but < 7 cm

T2:Tumor greater than 7 cm in greatest dimension is limited to the kidney

T2a:Tumor > 7 cm, but <10 cm

T2b:Tumors > 10 cm, limited to the kidney I

T3:Tumor extends to major vessels or perinephric tissues but unilaterally to adrenal

it does not extend into the gland and beyond Gerota’s fascia.

T3a:The tumor extends substantially into the renal vein or its segmental (muscular) branches, or the tumor does not invade the perirenal and/or renal sinus fat (peripelvic fat), but does not extend beyond Gerota’s fascia.

T3b:Tumor extends greatly into the vena cava below the diaphragm

T3c:Tumor extends substantially above the diaphragm into the vena cava or invades the wall of the venacava

T4:Tumor spreads beyond Gerota’s fascia (including ipsilateral-tumor-side spread to adrenal gland)

N – Regional Lymph Nodes: N0:There is no regional lymph node metastasis, N1:Metastases in regional lymph nodes

M – Distant Metastasis: M0:No distant metastases M1:Distant metastasis

p(pathological)TNM staging

  • STAGE I: T1, N0, M0

  • STAGE II: T2, N0, M0

  • STAGE III: T3, N0, M0 or T1, T2, T3 +N1, M0

  • STAGE IV: T4, Any N, M0 or Any T, Any N + M1

How the Disease Will Proceed Related Data-Prognosis

The stage of cancer is of course very important in determining the course of the disease and statistically predicting the expected life expectancy. However, other factors should be considered when determining the prognosis and treatment of people with Stage IV (metastatic) renal cell carcinoma. Two commonly used systems are the Memorial Sloan Kettering Cancer Center (MSKCC) criteria and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. These two systems use 5 or 6 factors that, when combined, place people in low, medium and high risk groups.

The MSKCC system includes:

  • High blood lactate dehydrogenase (LDH) level

  • high blood calcium level

  • measure of anemia

  • Less than one year from diagnosis to need for systemic therapy (targeted therapy, immunotherapy or chemotherapy)

  • Poor performance status (a measure of how well a person is able to do normal daily activities)

The IMDC system includes:

  • High white blood cell count (neutrophils)

  • High platelet cell count

  • high blood calcium level

  • Anemia

  • Less than one year from diagnosis to need for systemic therapy (targeted therapy, immunotherapy or chemotherapy)

  • Poor performance status (a measure of how well a person is able to do normal daily activities)

Patients are grouped according to the presence or degree of these factors: If none of the above factors are present, they are considered low risk and have a good prognosis. Having 1 or 2 factors is considered intermediate risk and has a moderate prognosis. Having 3 or more of these factors indicates high risk, poor prognosis, and less likely to benefit from certain treatments.

For kidney cancers, this estimate is grouped into local, regional, and distant stages of cancer.

  • Localized:There are no signs that the cancer has spread beyond the kidney.

  • Local:Cancer has spread outside of the kidney to nearby structures or lymph nodes.

  • Far:It includes cancers that have spread to distant parts of the body, such as the lungs, brain, or bones.

The 5-year relative survival rates for Kidney cancer by these groups are:

  • Localized disease: 93%

  • Regional Spread: 70%

  • Distant Metastasis: 13%

  • If all groups are combined, the average life expectancy of 5 years is 75%.

Kidney Cancer Treatment

Periods of the disease

Kidney cancer has different stages and treatment alternatives are determined accordingly. If the tumor is limited to the kidney and has not spread, it is classified as localized kidney cancer, if the tumor has grown out of the kidney to the surrounding tissue, has spread to the veins, adrenal gland and lymph nodes, locally advanced kidney cancer and if it has spread to distant lymph nodes or other distant organs, it is grouped as metastatic disease.

Kidney Cancer Surgery

Chemotherapy and radiotherapy are not very effective for kidney cancer, the main treatment is surgery. Sometimes surgery alone is often sufficient. Depending on the stage and location of the cancer and some other factors, the entire cancerous kidney and surrounding tissues are surgically removed, which is called radical nephrectomy. In addition, the adrenal gland (the small organ that sits on top of each kidney) and nearby lymph nodes can also be removed if needed. Or, in some selected patients, only the cancerous part of the kidney is removed, which is called partial nephrectomy or partial nephrectomy.

Radical Nephrectomy

Open radical nephrectomy surgery: In this surgery, the surgeon removes your entire kidney, the ipsilateral adrenal gland, part of the kidney duct (ureter), nearby lymph nodes, and fatty tissue around the kidney. Although removal of the adrenal gland is part of a standard radical nephrectomy, it may not be removed in some cases where the cancer is in the lower part of the kidney and away from the adrenal gland. If the tumor has grown from the kidney to the renal vein (the vein that removes the dirty blood from the kidney) and the inferior vena cava (the large vein that empties into the heart), the heart may need to be stopped for a short time, such as in open heart surgery, to remove the tumor inside the vein.

Laparoscopic nephrectomy: To remove the kidney, small holes are made in the abdomen and special long instruments are inserted through the incisions. A laparoscope is a long tube with a small video camera at the end. This allows the surgeon to see inside the abdomen. In the operation, a small incision is made in the lower abdomen to remove the kidney mass, usually in order to remove the kidney mass.

Robotic-assisted laparoscopic nephrectomy: This approach uses a robotic system to perform laparoscopic surgery remotely. The surgeon sits on a panel some distance from the operating table, from which he controls the robotic arms.

Kidney Sparing Surgery (Partial-Partial Nephrectomy)

Open Partial nephrectomy (nephron-sparing surgery): In partial nephrectomy, the surgeon removes only the cancer-containing part of the kidney and leaves the rest of the kidney. It is usually done to remove single small tumors (less than 4 cm) and may sometimes be required to remove larger tumors (up to 7 cm). Studies show that long-term outcomes are about the same as removing the entire kidney. Thus, the remaining part of the kidney continues its normal function.

Partial nephrectomy is not preferred if the tumor is in the middle of the kidney, is very large, has more than one tumor in the same kidney, or if the cancer has spread to lymph nodes or distant organs.

Laparoscopic partial nephrectomy and robotically assisted laparoscopic partial nephrectomy:

Regional Lymph Removal-Lymphadenectomy

Although the removal of regional lymph nodes during radical nephrectomy surgery is a matter of some debate, it at least gives us an idea in terms of correct staging after surgery, and there is information about its positive effect on the course/prognosis of the disease. There is a consensus on imaging methods to remove enlarged lymph nodes or abnormal lymph nodes during surgery.

Removal of the Adrenal Gland (adrenalectomy)

Although removal of the adrenal gland is normally a standard part of radical nephrectomy, removal may not be necessary if the cancer is in the lower part of the kidney (away from the adrenal gland) and imaging tests show that the adrenal gland is unaffected. Just like with lymph node removal, this is decided on an individual basis.

Removal of Metastases

In about ⅓ of kidney cancers, when first diagnosed, it has spread (metastasized) to other parts of the body, that is, it is in the metastatic disease group. Lungs, lymph nodes, bones, and liver are the most common sites of spread. For some patients, surgical removal of the foci in these regions has been found to contribute positively to the course of the disease and survival.

Risks and Complications of Surgery

Apart from the possible risks of any surgery and anesthesia, the risks of other possible kidney surgeries are:

  • Damage to internal organs and blood vessels (such as spleen, pancreas, aorta, vena cava, large or small intestine) during surgery

  • pneumothorax

  • Surgery site hernia

  • Urine leakage into the abdomen (after partial nephrectomy)

  • Kidney failure (if the remaining kidney does not work well)

Ablation and Other Local Treatments for Kidney Cancer

Surgical removal of kidney cancer is the mainstay treatment. However, some other treatments can be used for the treatment of patients with kidney tumors who have too many problems to undergo surgery or who do not want to have surgery. These approaches are generally considered for small (no larger than 4 cm) kidney cancers.

Cryotherapy (cryoablation): Cryotherapy refers to the process of freezing the tumor with special tools to destroy the tumor. A hollow needle is inserted into the tumor through the skin (percutaneously) or during laparoscopy. Through this channel, the tumor is frozen with freezing gases and forms an ice ball that kills the tumor. During the procedure (with ultrasound, CT, or MRI scans) images of the tumor are carefully viewed or tissue temperature measured to ensure that the tumor is destroyed without causing too much damage to nearby tissues. Possible complications include bleeding and damage to the kidneys or other nearby organs.

Radiofrequency ablation (RFA): Radiofrequency ablation is a method that uses high-energy radio waves to heat and kill the tumor (ablation). A needle-like stent is inserted through the skin into the tumor area. Probe placement is guided by ultrasound or CT scanning. After it is placed in place, the tumor is heated with an electric current/radiofrequency waves from the tip of the probe to try to destroy it. It is a procedure that generally does not require hospitalization and is performed under local anesthesia. Major complications are rare, but there may be bleeding and damage to the kidneys or other nearby organs.

Active Monitoring for Kidney Cancer

For some patients with these small kidney tumors (less than 4 cm), it may be an option to not give treatment at first and watch carefully to see if the tumor is growing. Follow up with imaging tests (ultrasound, CT or MRI scan) every 3 to 6 months. If it grows rapidly or is larger than 4 cm, the tumor is surgically removed or otherwise treated (with cryotherapy or RFA). Sometimes a biopsy may be done before deciding to monitor the tumor to see if the tumor is indeed cancer.

Radiation Therapy for Kidney Cancer

As is known, radiotherapy is not very effective in kidney cancer. If the patient is not healthy enough to have surgery or has only one kidney, radiotherapy-radiation can be used for kidney cancer. Radiotherapy can be used to cancerous kidney and/or areas of metastasis. In addition, radiation therapy; It can be used to relatively relieve the symptoms of cancer, such as pain and bleeding associated with a tumor, or to alleviate problems caused by the spread of cancer (especially to the bones or the brain). Complications include; skin changes (similar to sunburn) and hair loss in areas where radiation passes through the skin, nausea, diarrhea or fatigue.

Renal Vascular Embolization

If the patient is unsuitable for surgery and is causing bleeding and pain, he may recommend renal artery embolization. This treatment is only recommended when surgery is inappropriate or high-risk. By entering the inguinal region with a small catheter from the vein, the vessels around the kidney are reached and these vessels are blocked with plugs, and because the tissue cannot be fed, it dies-necroses and is cleared by the body.

Targeted Therapy for Kidney Cancer-Smart Drugs

As we learn more about changes in cancer-causing cells, smart drugs have been developed that target some of these changes. These targeted smart drugs work by blocking angiogenesis (the growth of new blood vessels that feed cancers), or important proteins (called tyrosine kinases) in cancer cells that help them grow and survive. Some targeted drugs affect both.

Immunotherapy for Kidney Cancer

Various types of immunotherapy can be used to treat kidney cancer.

Checkpoint inhibitors (Immune checkpoint inhibitors)

The basis of the immune system is T cells, which are white blood cells that are activated if necessary by distinguishing the body’s healthy cells from foreign and unhealthy cells by using the proteins on their surfaces with the key-lock principle. These T cells have ‘Brakes’ on their surface that prevent activation of the immune response when not needed. Here, tumor cells use these brakes to trick the immune system cells, T cells cannot recognize tumor cells. Tumor cells that manage to blind the immune system increase and spread. It targets proteins called CTLA-4 and PD-1, which are among these brakes that stop T cells. If these proteins are stopped, the immune system starts to see and recognize the tumor cells and fights them and ensures that they are destroyed. Treatment using drugs that fight and stop these proteins is called “immune checkpoint therapy”. Antibodies that bind to and block CTLA-4 and PD-1 proteins are used, called “immune checkpoint” inhibitors. In clinical trials, long-term improvement has been achieved in metastatic cancers, especially in treatments targeting PD-1. It has many side effects. Sometimes the immune system starts attacking other parts of the body, which can cause serious problems with the lungs, intestines, liver, hormone-producing glands (such as the thyroid), kidneys, or other organs. Sometimes these side effects can be life-threatening.

The only handicap for this treatment so far is that they don’t use the PD-1 or CTLA-4 proteins to trick the immune system of every tumor cell. You cannot prevent tumors that do not use this method by inhibiting this method. Therefore, it is necessary to be sure whether the tumor uses these proteins or not. For this purpose, laboratory tests are used to understand whether the tumor carries PDL-1, which activates PD-1.

The PD-L1 test helps determine whether a patient would benefit from “immune checkpoint therapy”. The test can be run from tumor tissue or blood. A PD-L1 test measures how much PD-L1 a tumor produces. Tumors that produce high amounts of PD-L1 are more susceptible to treatment than those that produce less. While it can be helpful in determining which patient may respond to medications, testing is not infallible. Some tumors that test for PD-L1 at high levels may not respond to treatment, and at low levels there may be a strong response. Cancer cells are complex, and different factors can affect how sensitive they are to these drugs.

1- PD-1 inhibitors: Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are drugs that target PD-1, a protein on immune system cells (called T cells) that normally helps prevent these cells from attacking other cells in the body. By blocking PD-1, these drugs increase the immune response against kidney cancer cells. This can usually shrink some tumors or slow their growth.

cytokines

Cytokines are small proteins that strengthen the immune system in general. Man-made versions of cytokines such as interleukin-2 (IL-2) and interferon-alpha are sometimes used to treat kidney cancer in very specific circumstances. Both cytokines can cause cancer to shrink in a small percentage of patients.

Interleukin-2 (IL-2): In the past, IL-2 was widely used as first-line therapy for advanced kidney cancer and may still be beneficial for some patients. However, it has serious side effects, so it may only be preferred for people who are healthy enough to tolerate the side effects and for cancers that do not respond to targeted drugs or other types of immunotherapy. Administration of high doses of IL-2 seems to offer good chances of shrinking the cancer, but this causes serious side effects, so it is not used in people with poor general health. Special care is needed to diagnose and treat these more side effects. These side effects are usually severe and rarely fatal. Only centers experienced in the use of these drugs should give this treatment. IL-2 is given intravenously (IV).

Possible side effects of IL-2

  • Overstrain

  • low blood pressure

  • Fluid buildup in the lungs

  • difficulty breathing

  • kidney damage

  • Heart attack

  • intestinal bleeding

  • diarrhea or abdominal pain

  • High fever and chills

  • rapid heartbeat

  • mental changes

Interferon-alpha. Interferon has less serious side effects than IL-2, but does not appear to be as effective when used alone

Chemotherapy for Kidney Cancer

Chemotherapy refers to the use of anti-cancer drugs within the framework of a certain protocol. uses. It can be used intravenously or as an oral pill. It is not a standard treatment for kidney cancer, as kidney cancer cells often do not respond well to chemotherapy. Some chemotherapeutic drugs such as cisplatin, 5-fluorouracil (5-FU), and gemcitabine have been shown to help a small number of patients. nowadays, more chemotherapeutics are usually only offered as the last option after targeted drugs and/or immunotherapy have been tried. They are given in the form of cures within the framework of a certain protocol. Chemotherapy drugs attack rapidly dividing cells, so they are usually effective against cancer cells. But other cells in the body also divide rapidly, such as in the bone marrow (where new blood cells are made), the inner surfaces of the mouth and intestines, and hair follicles. These cells are also likely to be affected by chemotherapy, which can lead to some side effects. The side effects of chemotherapy depend on the type of drug, the amount taken, and the duration of treatment. These side effects usually go away after treatment ends. There are usually ways to prevent or reduce them.

Possible side effects can include:

  • hair loss

  • mouth sores

  • Loss of appetite

  • Nausea and vomiting

  • diarrhea or constipation

  • Increased chance of infection (due to low white blood cell count)

  • Easy bruising or bleeding (due to low blood platelet count)

  • Fatigue (due to low red blood cell count)

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