This type of tumor is caused by the uncontrolled growth of cells and can be:

  1. Benign (not cancerous),
  2. Malignant (cancerous and can be deadly).

The kidney is the organ of the urinary system that serves for the formation and expulsion of urine, other organs of this apparatus are:

  • Ureteres
  • Bladder
  • Urretra.

Kidney tumors account for 3% of all tumors and mainly affect people over 40 years of age.
It usually occurs only in the left or right kidney, but can also be bilateral (2-5% of cases).

In 1% of cases the tumor extends to the ureter.
Kidney cancer affects more men than women, the incidence is 17.9 new cases in 100,000 in men and about 10.3 cases in 100,000 women.

 


Types and Classification of Kidney Cancer

The tumor in the kidney grows at different rates, has different prognoses and reacts differently to treatment.
Renal cell carcinoma is made up of different types of cells.

Kind Frequency
Clear cells 75-80%.
Papillary 10-15%,
Chromophobe 5%
Oncocytoma 3-7%
From the collecting duct  <1%

The researchers believe that clear cell carcinoma and papillary originate from the proximal tubule epithelium.
In addition, it is believed that chromophobic renal carcinoma, oncocitoma and duct collector originate from the distal nephron, probably from the collecting tubule epithelium.
Source: Renal Cell Carcinoma – Paul Cairns

Clear Cell Carcinoma
Cancer cells are very light under the microscope.
Clear cell renal carcinoma may be sporadic (> 96%) or familial (<4%).
It usually originates from an inherited mutation caused by von Hippel-Lindau syndrome (VHL) of a gene located on chromosome 3p.
It is the most common type of renal cell carcinoma.
Clear cell tumor was identified in some hybrid tumors.

Chromophobic Carcinoma
Cells from this tumor are pale, as in the clear cell tumor.
However, they are much larger.
Chromophobic renal cancer grows slowly.
Generally, in people with BHD syndrome does not form metastases. 
Chromophobic renal carcinoma is considered less aggressive than other forms of renal carcinoma.
Chromophobic cancer accounts for about 23% of HDL-related renal carcinomas.

Papillary carcinoma
These tumors form small finger-like projections (called papillae) in most cases.
Papillary renal carcinoma (especially type 2) can be aggressive and cause metastasis.

Oncocitoma Oncocytomas
are considered benign cancers of the kidneys.
Although benign, oncocytoma can damage the kidneys if it grows in regions that are important for kidney function or blood flow.
This type of cancer does not spread to other parts of the body.

Carcinoma of Collecting Ducts (Bellini)
This type occurs mainly in young adults.
In this type of tumor, the cells may look like jagged tubes under a microscope.
It is a rare cancer, but it can be aggressive.
It may also be resistant to traditional treatments that are effective for other types of kidney cancer.

Hybrid Cancer Hybrid
tumors are a combination of two types.
Several hybrids have been identified in BHD-related cancers, including oncocytic, chromophobe and clear cell.
In a study of 34 individuals with BHD-related renal tumors, about 67% of the tumors are oncocytic / chromophobic hybrid.

Other types of cancer
There are other types of benign kidney tumors in patients with HDh, such as renal angiomyolipomas that usually occur along with tuberous sclerosis.

 

Kidney Cancer Risk Factors

  1. Cigarette smoke
  2. Obesity (especially in women)
  3. Exposure to heavy metals, solvents and coal derivatives
  4. Dialysis
  5. Esclerose tuberosa
  6. Renal transplantation : immunosuppressive therapy increases risk 80-fold
  7. Phenacetin abuse (analgesic)

 


Causes of Kidney Cancer

The exact cause of the cancer has not yet been identified.
Medical researchers believe that frequent exposure to chemical toxins, smoking and the side effects of medications are the triggers for the development of cancer.
People who smoke have a 2-4 times higher risk of getting sick than nonsmokers.

The chemicals that can cause kidney cancer are:

  • Asbestos,
  • Cadmium,
  • Benzene,
  • Biological solvents,
  • Some herbicides.

Other risk factors include:

In children, the most frequent form is Wilms’ Tumor, while in adults it is clear cell carcinoma.
The syndrome Birt-Hogg-Dube (BHD) is a rare genetic disease (1 in 200,000) , characterized by changes in FLCN gene (encoding folliculin hormone).
BHD is characterized by the development of:

  1. Benign cutaneous tumors (fibrofoliculoma),
  2. Pulmonary cysts that can cause pulmonary collapse ( spontaneous pneumothorax ),
  3. Carcinoma renal.

 


Symptoms of Kidney Cancer

In the first phase the cancer in the kidney is asymptomatic.
With the progression of the disease some symptoms can manifest themselves such as:

The disease can spread from one kidney to another and to other organs, especially:

  1. Lungs ,
  2. Lymph nodes ,
  3. Liver ,
  4. Bone ,
  5. Adrenal gland,
  6. Spleen,
  7. Colon,
  8. Brain,
  9. Skin.

The lymph nodes adjacent to the diseased kidney may swell .

Early Signs and Symptoms of Kidney Cell Carcinoma
In some cases it is difficult to detect early kidney cancer because it is not clearly manifested.
The symptoms appear only with the progression of the disease.
However, there are some signs that may help in the early diagnosis of the disease:

  • The presence of blood in the urine (hematuria). Urine may be reddish or light yellow in color
  • Anemia due to blood loss
  • Pale skin
  • Persistent presence of kidney infections , which may take some time to heal
  • Deaf or heavy pain, especially in the lower back
  • Unexplained weight loss
  • High blood pressure
  • General weakness of the body and feeling sick
  • Intermittent fever and tiredness accompanied by excessive sweating
  • Formation of a ledge on one side of the abdomen
  • Swelling above the kidneys
  • Constipation and excessive thirst due to increased levels of calcium in the blood. Calcium increases because there are bone lesions.
  • Polycythemia , a condition that increases the volume (in percentage) occupied by the red blood cells in the blood. In kidney cancer, this occurs due to excessive production of erythropoietin.

Since this disease can cause many different symptoms that can be mistaken for disorders of other organs, it has been defined as the great treat.

 


Diagnosis of kidney cancer

Usually, the doctor diagnoses a tumor after an abdominal computed tomography or ultrasonography performed for other reasons.

Ultrasonography is a very precise technique because it allows to distinguish well vascularized lesions in relation to non-vascularized and non-tumoral lesions, for example cysts . It has an accuracy of over 95%.
In case of doubt, your doctor prescribes a CT scan to help you understand:

  1. The type of mass,
  2. The size of the tumor,
  3. If there are metastases.

The blood tests and urine can show the values of certain substances (eg, creatinine in the blood) that indicate whether the kidneys are functioning properly.
When the presence of the mass is confirmed, the doctor can perform the biopsy to understand if the tumor is aggressive and before making an operation to remove the mass.
In addition to these techniques, it is possible to perform an ultrasound  to diagnose cancer in the kidney.
In some cases, the cancer is diagnosed when it is already large, for example 10 cm or more.

 


Staging of kidney cancer

Stage I : The cancer is confined to the kidney with a size  smaller than 7 cm. It has not spread to the lymph nodes or distant organs.

  • T1a : the tumor is smaller than 4 cm.
    T1b : the tumor has dimensions between 4 and 7 cm.

Stage II : The tumor is limited in the kidney and is larger than 7 cm. It has not spread to the lymph nodes or distant organs.

  • T2a : Tumor size is between 7 and 10 cm.
  • T2b : the tumor is larger than 10 cm.

Stage III  – There are tumors of any size with spread to adjacent lymph nodes in the kidney or large veins that attach the kidneys to the heart (a tumor venous thrombus may form). Tumors that invade other adjacent organs or those with distant metastases are not included at this stage.

  • T3a : The tumor has spread to the renal vein or its branches, to the kidney fat or to the inside of the kidney, pelvis and kidney (which store urine before sending it to the bladder). The tumor did not grow beyond Gerota’s fascia.
  • T3b : the tumor grew in the inferior vena cava, below the diaphragm muscle.
  • T3c : the tumor has spread to the vena cava above the diaphragm muscle and to the right atrium of the heart or to the walls of the vena cava.

Stage IV  This stage includes the different types of cancer made from cells that invade  adjacent organs such as the colon (large intestine) or the abdominal wall and those with distant metastases.

T4  – the tumor has spread to areas beyond the Gerota fascia and extends to the adrenal gland above the same kidney.


Treatment for Kidney Cancer

In recent years different treatment options have been developed for the effective cure of kidney cancer.
Today, this type of cancer can be treated with:

  1. The surgery,
  2. Cryoablation,
  3. Radiofrequency ablation,
  4. Embolization,

According to NCCN (National Comprehensive Cancer Network) guidelines , the first treatment for localized renal cell carcinoma (up to stage III) is surgery.
If the tumor is not metastatic, no other medical treatment or radiotherapy will be performed.
In stage IV , the surgeon intervenes to remove the kidney and metastases if the patient can improve with a radical nephrectomy (total removal of the kidney).
The oncologist only intervenes in the more advanced phases with the drug therapy.
Sometimes only systemic medical therapy is performed:

  1. Chemotherapy,
  2. Biological therapy (target).

 

Surgical operation for kidney cancer

Surgery can be of two types:

  1. Removal of the affected kidney along with adjacent healthy tissues and lymph nodes (nephrectomy)
  2. Removal of the tumor with a small amount of healthy tissue around (partial nephrectomy), in stages I (<7 cm) and II (> 7 cm).
    The partial technique is also indicated when it is not possible to remove a lot of renal mass (a bilateral tumor, a patient who has only one kidney or someone suffering from chronic renal failure).

If the renal mass is <10 cm, this surgery can be performed in laparoscopy, that is, with 3 small incisions (less than 1 cm) instead of a long cut.
With this technique, there are:

  1. Fewer surgical complications,
  2. Shorter hospitalization.

If a patient has only one metastasis, surgical removal of metastasis (especially at the lung level) improves patient survival and in some cases can also cure the patient.
Therefore, unlike other neoplasms, the presence of a metastatic nodule is not a contraindication to surgery.

Cryoablation and radiofrequency ablation
In cryoablation the cancer cells freeze at extreme temperatures.
Generally a hollow needle is inserted into the tumor through the skin and a pressurizedgasin the needle is used to freeze the cancerous cells.
In ablation radiofrequency cancer cells are burned using electric currents.
To do this, a special needle is inserted into the tumor, allowing the passage of electric current.

Embolization
Embolization blocks the supply of blood and oxygen to the tumor to reduce it.
In this procedure, a special substance is injected into the main blood vessel that carries blood to the kidneys.
This deprives the tumor of the oxygen and the nutrients it needs to grow.
This procedure is also known as arterial embolization and is sometimes done before surgery.

 

Drug Therapy for Kidney Cancer

The systemic therapy includes:

  1. Therapies with cytokines,
  2. Target therapies, including inhibitors of VEGF, VEGFR and mTOR,
  3. Bisphosphonates to protect skeletal integrity, such as supportive treatment.

Generally, renal cell carcinoma does not respond to chemotherapy .

The immunotherapy with cytokines (interferon, interleukins or both) may have a small improvement in survival (with a not particularly toxic treatment, the patient with a one – year life expectancy can live two years).
Today they are no longer used because there are more effective therapies: target therapy.

The biological therapy uses specific drugs to stimulate the immune system to destroy cancer cells.
Target therapy is another treatment that uses drugs to block abnormal signals that play an important role in tumor growth and proliferation.

The molecular drugs have completely changed the treatment:

  1. Sorafenibe,
  2. Sunitinibe,
  3. Temsirolimus,
  4. Bevacizumabe,

The most recent are:

  1. Pazopanibe,
  2. Everolimus.

These drugs have an important effect on angiogenesis (formation of new blood vessels).
As the neoangiogenic component in the renal tumor is very important, these drugs are very effective.
There is an improvement in life expectancy:

  1. Total,
  2. No worsening or progression of the disease.

The radiation has very few indications, because the renal cell carcinoma is a tumor that usually does not respond to radiation therapy.
Then the doctor prescribes to:

  1. Reduce pain caused by bone metastases ,
  2. Compression of the spinal cord,
  3. Brain metastases.

The most important target is VEGF (vascular endothelial growth factor) , a multifunctional protein that induces the growth of endothelial cells, promotes angiogenesis and vascular permeability.
When VEGF binds to a receptor on the cell membrane, the kinases (enzymes) are activated within the cell and cause some cellular reactions.
The consequences are:

  1. Higher permeability of blood vessel walls,
  2. Cell proliferation,
  3. Increased endothelial survival.

You can use different types of drugs:

  1. Antibodies that bind to VEGF directly into the bloodstream , such as Bevacizumab. In this way, VEGF can not be bound to the receptor, therefore, the biological effect of this substance is avoided.
  2. VEGF-R inhibitors that block signals within the cell , such as Sunitinibe, Sorafenibe, Pazopanibe.

Bevacizumab is given intravenously.
Sunitinib and sorafenib are oral medications.
Today, sunitinib is the drug of choice in the treatment of renal carcinoma.

The sorafenib is suitable for advanced carcinoma of the kidney and has an inhibitory effect:
1. tyrosine kinase RAF1.
2. Tyrosine kinase receptors of VEGF-R2, PDGF-R, FLT3 and c-KIT.

The temsirolimus is a specific inhibitor of mTOR kinase.
It is a protein that is involved in the phases of the cell cycle:

  1. In cell proliferation,
  2. In survival mechanisms.

Thus, Temsirolimus blocks the cellular response to growth factors and nutrients.
A similar drug is Everolimus, which inhibits the reactions they cause:

  1. The proliferation,
  2.  Angiogenesis,
  3. Aggressiveness of the tumor.

Which drugs to choose? 
For patients with a low risk (based on certain specific parameters), your doctor prescribes Bevacizumab or Sunitinib.
For patients at high risk, Temsirolimus is the most indicated medicine.

The diet for cancer is crucial to fighting mass growth.

Follow-Up Controls After Removal of Kidney Cancer or to Prevent Recurrence
In the case of stage IV cancer, the program consists of:

  1. Clinical evaluation, blood tests, chest x-ray, and computed tomography of the abdomen / pelvis after 3 and 6 months.
  2. Subsequently, this program is repeated every 6 months for 3 years,
  3. After the first 3 years, it is repeated every year.

 


What is the life expectancy? Prognosis of kidney cancer

Survival
rate The survival rate is determined after the identification of the tumor stage.

5-year survival of patients with renal cell carcinoma

Stadium Survival
1 81%
2 74%
3 53%
4 8%

Fonte: American Cancer Society

The prognosis of metastatic kidney cancer is pessimistic because these patients are at a very advanced stage of the disease.

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