FAQ : Kidney cancer

Kidney cancer is a disease characterized by the abnormal and uncontrolled growth of malignant cells in kidney tissue. It usually develops in kidney tubule cells that are responsible for filtering blood. Kidney cancer primarily affects men over the age of 60, with risk factors such as smoking, obesity, hypertension, and a family history. In France, the incidence of kidney cancer has continued to increase in recent years. According to estimates, in 2023, 17,141 new cases were diagnosed.

• Clear cell subtype(ccRCC) (70-80%) : the most frequent, characterized by cells rich in lipids and glycogen.
• Papillary subtype(cCRP) (10-15%) : growth in papillary structures, subdivided into type 1 and type 2.
• Chromophobic subtype (5-7%) : larger cells and homogeneous appearance, generally less aggressive.

Collector tube carcinoma (rare) : aggressive and with a poor prognosis.

Medullary carcinoma(very rare) : mainly affects young patients with sickle cell anemia.

Nephroblastoma (Wilms tumor)

Cancer pediatric most common renal, of embryonic origin.

The main genetic mutations found in kidney cancer are as follows:

• VEGF — overexpression: stimulates angiogenesis.
• PD-L1 — overexpression: promotes immune escape, target of immunotherapies.
• MTOR/PI3K/AKT — activation: stimulates cell growth and survival

Other molecular abnormalities:

• VHL (Von Hippel-Lindau) — loss of function
• MET (hepatocyte growth factor receptor) — overexpression
• PBRM1 (SWI/SNF complex) — loss of function
• TP53 (tumor suppressor gene) — loss of function
• SETD2 (DNA methylation) — loss of function
• BAP1 (ubiquitin and apoptosis) — loss of function
• FH (fumarate hydrase) — loss of function

The TNM score is a classification system used to assess the stage of a cancer, plan treatment, and predict prognosis.

Three parameters must be taken into account:

• The T describes the size and extent of the primary tumor
• The N indicates whether the cancer faces a regional lymph node extension
• The M indicates whether the cancer has spread to other parts of the body, called metastases

Kidney cancer is classified into four stages according to the TNM classification. Stage I corresponds to a tumor of less than 7 cm limited to the kidney. Stage II involves a larger tumor, larger than 7 cm, but still confined to the kidney. Stage III indicates local extension to nearby tissue or regional lymph nodes, without distant metastasis. Finally, stage IV is characterized by the spread of cancer cells to distant organs, such as the lungs, bones, or liver. Treatment varies by stage and may include surgery, targeted therapies, and immunotherapy.

The treatment of kidney cancer is based on a personalized approach that combines surgery, targeted therapies, immunotherapy and, in some cases, radiation therapy, depending on the stage of the disease, the histological type and the general condition of the patient.

Surgery is the gold standard treatment for localized kidney cancer. Various surgical procedures can be found:

• Partial nephrectomy : removal of the tumor while keeping the kidney (stage I and some stages II)
• Total nephrectomy: complete removal of the kidney (larger or more invasive tumors)

Chemotherapy, which involves using cytotoxic drugs to destroy cancer cells, is generally not very effective in treating kidney cancer, especially for renal cell carcinomas. Indeed, these tumors are often resistant to conventional chemotherapeutic agents because of their DNA repair mechanisms and their low sensitivity to apoptosis induced by these treatments.

As a result, the management of kidney cancers is based more on targeted therapies and immunotherapy. However, in some rare forms, such as collecting tube carcinomas or pediatric tumors such as nephroblastoma (Wilms tumor), chemotherapy may be used in addition to surgery and other treatments.

Radiation therapy is not very effective on kidney cancer because it is radiation resistant. It is therefore not used in curative treatment. However, radiotherapy can be used for pain relief to treat bone or brain metastases.

Targeted therapy is a drug treatment that specifically targets genetic or molecular abnormalities or alterations present in cancer cells or other diseased cells.

Unlike conventional treatments such as chemotherapy that act on all cells in the body, targeted therapies work more selectively, by blocking or inhibiting specific proteins involved in the growth and proliferation of cancer cells or in other diseases.

Targeted therapies are often used in combination with other treatments such as chemotherapy or radiation therapy. They are being used more and more in the treatment of cancer.

In the case of kidney cancer, among the most used targeted therapies, we find for example:

• VEGFR inhibitors (sunitinib, pazopanib, axitinib) : block angiogenesis.
• mTOR inhibitors(temsirolimus, everolimus) : disrupt cell growth.

Immunotherapy is a treatment that stimulates or changes the immune system to help fight cancer. It uses antibodies, vaccines, or other agents to enhance the body’s ability to detect and destroy cancer cells. This treatment can be used alone or in combination with other treatments such as surgery, chemotherapy, or radiation therapy.

Among the immunotherapies most used in kidney cancer are immune checkpoint inhibitors:

• Anti-PD-1 (nivolumab, pembrolizumab)
• Anti-PD-L1 (avelumab)
• Anti-CTLA-4 (ipilimumab)

In combination with targeted therapies, these treatments improved the survival of stage IV patients.