What is renal/kidney cancer, types, and diagnosis?

The abnormal growth of cells in the kidney is termed kidney cancer These cells gradually multiply and form a mass, referred to as a tumor. Cancer begins in about 9 out of 10 patients when a mass forms in the blood-filtering tubes of the kidney. The process by which a malignant tumor spreads to other tissues and vital organs is known as metastasis.

Types of Kidney Cancer

There are 4 different types of kidney cancer:

1. Renal Cell Carcinoma (RCC): The most common type of renal tumor in adults. They can be clear cell carcinomas, chromophobes, papillary, or collecting duct tumors. The clear cell type is the most common among all the subtypes.
2. Transitional Cell Cancer: This type of cancer accounts for about 6 to 7% of kidney carcinomas.
3. Renal Sarcoma: The least common form of renal tumor, accounting for only 1%.
4. Wilms Tumor: The most common type among children, kidney cancer is often discovered at an early stage when the cancer is small and confined to the kidney.

Aetiology

The exact cause of kidney cancer has been unknown up until now. Cancer usually begins due to mutations in certain genes that normally keep cell division in check. Abnormal growth of cells occurs when this system fails to function properly. In most cases, these mutations are acquired over a lifetime. In some cases, certain conditions inherited from one’s parents cause these mutations and increase the risk of kidney cancer.

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Inherited Disorders Include:

• Von Hippel-Lindau disease
• Hereditary papillary renal carcinoma
• Birt Hogg-Dube (BHD)
• Succinate dehydrogenase deficiency
• Tuberous sclerosis
• PTEN hamartoma tumor syndrome (including Cowden syndrome)

Common causes/risk factors of kidney cancer include:

• Smoking: The longer a person smokes, the higher the risk of having kidney cancer.
• Obesity: The more overweight a person is, the higher the risk.
• High blood pressure:
  • Family history: If family members have had kidney cancer, there is a higher risk of acquiring the condition.
  • Radiation therapy: Women treated with radiation for cancer of their reproductive organs may have a slightly increased risk of developing kidney cancer.
  • Gene mutations: These can be inherited or acquired.
  • Long-term dialysis treatment: Dialysis is performed in cases of renal failure or if the kidneys are not functioning properly.
  • Tuberous sclerosis complex: This can cause intellectual disabilities, seizures, and the formation of tumors in many different organs.

Risk Factors

• Gender: Men have a higher risk of developing kidney cancer (> 60% of kidney cancer patients are men).
• Age: Most people are diagnosed between the ages of 55 and 74.
• Smoking: Men who smoke are about 50% more likely to develop kidney cancer; women who smoke are at a 20% increased risk.
• High blood pressure: Elevated blood pressure can increase the risk of developing kidney cancer.
• Kidney disease: Individuals who have undergone long-term dialysis or have chronic kidney disease have a greater risk.
• Environmental exposures: Individuals working with chemicals such as trichloroethylene, asbestos, benzene, benzidine, cadmium, herbicides, and vinyl chloride are at increased risk.

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Epidemiology

Likelihood of developing kidney and renal pelvis cancer according to age, stratified by gender:

Globally, there are over 400,000 new cases of renal cell carcinoma and over 170,000 deaths due to kidney cancer. RCC is a rare disorder among children. Men are predominantly affected by kidney cancer. From the table above, it can be understood that kidney cancer is mostly seen among the adult population. Kidney cancer is very uncommon among those younger than 45 years. It ranks as the 10th most common cancer among men and women. The lifetime risk of developing kidney cancer among men is 1 in 46 (2.02%), while for women, it is 1 in 80 (1.03%).

Pathophysiology

Kidney cancer originates in two principal locations in the kidney:

• Renal Tubule: Renal tubule cancers include renal cell carcinoma (RCC) and clear cell adenocarcinoma.
• Renal Pelvis: Renal pelvis carcinomas are transitional cell carcinomas.

There are 4 main stages of kidney cancer based on:

• The size of the tumor (“T”)
• Spread of cancer to the nearby lymph nodes ("N")
• Spread of cancer to other body organs ("M")
• This is known as the TNM staging system.

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Stages of Kidney Cancer

Stage I: The cancer is only within the kidney and has not spread. The tumor is less than 7 cm in size. If the tumor can be removed, it is most likely to be cured with surgery.

Stage II: If the cancer is larger than 7 cm but is still confined to the kidney, surgery is a good treatment option. The survival rate after surgery for stage II kidney cancer is still very high (five years).

Stage III: In this stage, kidney cancer has moved nearby or outside the kidney, e.g., the cancer spreads into the fat around the kidney, into the blood vessel coming out of the kidney, or into lymph nodes near the kidney.

Stage IV: The kidney cancer has spread widely outside the kidney, to the abdominal cavity, to the adrenal glands, distant lymph nodes, or to other organs such as the lungs, liver, bones, or brain. Ask your doctor about all treatment options and clinical trials.

Types of Kidney Cancer

Renal Cell Carcinoma

RCC is the most common type of kidney cancer in adults, occurring most often in men aged 50 to 70 years. The highest rates of RCC are seen in the Czech Republic and North America. The tumor arises from the cells of the proximal renal tubular epithelium. The genes whose alteration results in RCC formation include:

• Tumor suppressors (VHL, TSC)
• Oncogenes (MET)

There are two subtypes of RCC:

• Sporadic
• Hereditary

Both subtypes are associated with mutations in the short arm of chromosome 3, involving suppressor genes or oncogenes.

Transitional Cell Cancer

Transitional cell carcinomas, also known as urothelial carcinomas, arise from the specialized mucous membrane lining.

• The urinary bladder
• The lower part of the kidneys
• The ureters
• The proximal urethra

Most carcinomas in these parts of the renal system are transitional cell carcinomas. Genetic mutations involved in the pathogenesis of bladder cancer include:

• HRAS mutation
• Rb1
• PTEN/MMAC1 mutation
• NAT2 slow acetylator phenotype
• GSTM1 null phenotype

Industrial carcinogens associated with transitional cell carcinomas include:

• Aromatic amines
• Aniline dyes
• Aldehydes

Renal Sarcoma

This type of kidney cancer develops in the soft tissue of the kidney, including the capsule (the thin layer of connective tissue surrounding the kidney) and surrounding fat. Renal sarcoma begins in the blood vessels or connective tissue of the kidney.

Wilms Tumor (Nephroblastoma)

Wilms tumor has a triphasic appearance and consists of 3 types of cells:

• Stromal
• Epithelial
• Blastemal

Wilms tumor metastases to the lung are common. It can be divided into 2 pathologic categories:

• Favourable
• Anaplastic

The characteristic of Wilms tumor includes abortive tubules and glomeruli surrounded by spindle cell stroma. The stroma comprises:

• Striated muscle
• Cartilage
• Fat tissue
• Fibrous tissue

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Diagnosis of Kidney Cancer

Clinical Features:

• Blood in the urine (may appear pink, red, or cola-colored)
• Persistent pain in the back or side
• Loss of appetite
• Fever
• Tiredness
• Unexplained weight loss

Investigations

Urinalysis: About 2 to 5 people with kidney cancer have the presence of blood in their urine. A small sample of urine is tested in a lab. Urine cytology is also done to identify cancer cells in the urine sample.

Blood Tests: Kidney cancer cannot be diagnosed through blood tests, but a CBC (complete blood count) can show signs associated with kidney cancer, such as:

• Too few RBCs (anemia): This is a common sign of many kinds of cancer.
• Too many RBCs (erythrocytosis or polycythaemia): Certain kidney cancer cells make erythropoietin, which causes the bone marrow to make too many RBCs.
• A high blood calcium level indicates that cancer has started to affect the patient's bones.
• A high level of liver enzymes indicates that cancer has affected the liver.
• Raised ESR (erythrocyte sedimentation rate)
• Abnormalities of plasma proteins
• Disorders of coagulation

Imaging Tests:

1. CT Scan: A confirmatory test for the diagnosis of kidney cancer.
2. MRI Scan: Shows whether cancer has spread to the spine or brain.
3. Ultrasound: Shows whether the kidney tumor is a fluid-filled sac or a solid tumor.
4. Intravenous Pyelogram (IVP): Special dyes are used to look at kidneys, ureters, and bladders.
5. Angiography: Uses dyes and X-rays to look at the kidneys.

Biopsy

A thin needle is inserted through the skin to remove fluid or small pieces of tissue from the kidney after numbing. The sample is then sent to the pathologist.

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Management

The treatment depends on the TNM staging of the tumor. Treatment options include:

Surgery

Two main types of surgery are conducted for kidney cancer:

• Partial Nephrectomy: Where part of the kidney containing cancer is removed.
• Radical Nephrectomy: The entire kidney is removed.

A partial nephrectomy is performed when the tumor size is small (≤ 4 cm) and is easy to remove, with a lower incidence of cardiac and renal morbidity. Radical nephrectomy is performed in cases of larger cancers or if cancer has spread beyond the kidney. Kidney surgery can be done in two different ways:

• Open Surgery: A large incision is made in the stomach and back.
• Laparoscopic Surgery: Surgical tools are inserted through a small incision made by the surgeon.

Transitional cell carcinoma of the renal pelvis and ureter is usually treated by open or laparoscopic nephroureterectomy, but if the tumor is solitary and low grade, it can be treated endoscopically.

Ablation Therapies

Cancer cells are destroyed by ablation therapy through two methods:

• Cryotherapy (freezing method)
• Radiofrequency Ablation (heating method)

Targeted Therapies

Targeted therapies are recommended in cases of advanced cancer. Biological therapies include tyrosine kinase inhibitors, such as:

• Sunitinib
• Pazopanib
• Cabozantinib
• Tivozanib
• Nivolumab

mTOR (mammalian target of rapamycin) inhibitors may also be used, including:

• Temsirolimus
• Everolimus

Possible side effects depend on the types of medicines taken, including fatigue, diarrhea, hypertension, rash, sore mouth, tiredness, cough and shortness of breath, loss of appetite and weight loss, indigestion, and infertility.

Embolization

Embolization is a procedure used to block the blood supply to a tumor, resulting in its shrinkage. It is recommended for patients who are not in good health. During embolization, a dye is injected through a catheter to effectively block the blood vessel.

Radiotherapy

Radiotherapy is used to target or destroy cancerous cells. It slows the spread or progress of kidney cancer and is recommended in cases of advanced kidney cancer that has spread to other body parts (such as bones or the brain).

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Treatments for Advanced and Recurrent Kidney Cancer

• Surgery: If cancer cannot be fully removed, surgeons attempt to remove as much of the tumor as possible.
• Targeted Therapy: Focuses on specific abnormalities present within cancer cells. Targeted drug treatments can cause cancer cells to die by blocking these abnormalities.
• Immunotherapy: Utilizes the individual’s immune system to fight cancer. It works by blocking or interfering with the proteins produced by cancer cells that prevent the immune system from attacking them.
• Radiation Therapy: Used to reduce or control the symptoms of kidney cancer.

Clinical Trials: Research studies that allow testing of the latest advancements in kidney cancer treatment.

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