Metastatic Renal Cell Carcinoma - Treatment Approaches and Therapeutic Strategies

Introduction

Renal cell carcinoma (kidney cancer) or RCC, is the most common form of kidney cancer affecting adults. These cancers usually begin at the lining of the tubules present in the kidneys, which are responsible for filtering waste products from the body and excreting them out with urine. The term metastatic renal cell carcinoma implies kidney cancer that has spread to different parts of the body. This article highlights the stages of RCC and other management strategies for renal cell carcinoma.

What Is the Prevalence of Renal Cell Carcinoma?

Renal cell carcinoma accounts for almost 2.4 percent of total cancers based on data from GLOBOCAN (Global Cancer Observatory), with 8 percent in the metastatic stage.

Where Does Metastatic Renal Cell Carcinoma Spread First?

Metastatic renal cell carcinoma first involves the lymph nodes, followed by:

• Lungs.

• Bone.

• Liver.

• Brain.

• It can also involve ovaries and testicles in a few cases.

What Are the Stages of Renal Cell Carcinoma?

The staging of renal cell carcinoma helps to determine how advanced the cancer stage is and if it is localized or metastasized to different organs. Staging also helps to plan the management of renal cancer accordingly.

Different Stages of Renal Cancer Involve:

• Stage I RCC: The tumor size is less than 2.7 inches and is localized within the kidney only.

• Stage II RCC: The size of the tumor is more than 2.7 inches, but it has not metastasized (spread) beyond the kidney.

• Stage III RCC: The tumor varies in size but has spread to the surrounding kidney structures.

• Stage IV RCC: When the cancer has spread outside the kidney to different areas in the body like lymph nodes, lungs, or other body organs.

What Are the Strategies for the Management of Metastatic Renal Cell Carcinoma?

Metastatic renal cell carcinoma (mRCC) can be managed by the following strategies:

Immunotherapy: A high dose of interleukin-2 (IL-2) is an immunotherapy option for managing renal cell cancer by stimulating the immune system to attack the cancer cells. When given in large doses, IL-2 can also potentially shrink tumors. Immunotherapy using IL-2 might not be effective in all cases. A few side effects associated with immunotherapy using IL-2 are:

1. Low blood pressure.

2. Fluid within lungs.

3. Bleeding.

4. Chills.

5. Fatigue.

6. Lethargy.

Targeted Therapy: Targeted therapy involves:

1. Tyrosine Kinase Inhibitor (TKIs): Medications like Sunitinib, Axitinib, etc, can target the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), which are involved in angiogenesis (blood vessel formation). These drugs aim to inhibit the blood supply to tumors. TKIs are prescribed by doctors once or twice a day depending on the severity of the cancer spread. Some side effects associated with targeted therapy with TKIs are pain in the upper and lower extremities, nausea, and liver problems.

2. Immune Checkpoint Inhibitors: Medications like Nivolumab and Ipilimumab are used to target the immune system, specifically programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), to enhance the body's immune response against cancer cells.

3. mTOR (Mammalian Target of Rapamycin) Inhibitors: These drugs usually target the mTOR protein. The mTOR helps the tumor cells to grow. Mammalian target of Rapamycin (mTOR) inhibitors such as Everolimus, Temsirolimus, etc. help to target and inhibit mTOR protein formation, thereby restricting the growth of tumor cells. Everolimus is usually in tablet form and is prescribed once a day by the doctor. Temsirolimus is given intravenously (IV) once a week. A few side effects associated with mTOR inhibitors are rashes and increased cholesterol, weakness, lethargy, raised blood pressure, and fluid accumulation in the face and legs.

4. Anti-angiogenesis Therapy: All the tumor cells feed on the nearby vessels to grow and expand in size. Anti-angiogenesis therapy cuts off the blood supply to the tumor cells, thereby making tumor cells starve and restricting their growth. The drug Bevacizumab is given intravenously (IV) once every two weeks between 30 to 90 minutes for anti-angiogenesis therapy. Immunotherapy with the drug interferon alpha is also given simultaneously with this therapy.

A Few Side Effects Associated With This Therapy Are:

1. Loss of appetite.

2. Altered taste sensation after therapy.

3. Fainting.

4. Heartburn.

5. Weight loss.

6. Raised blood pressure.

7. Mouth sores.

Radiation Therapy: External beam radiation therapy is usually employed to target specific areas of metastasis and destroy the cancer cells, particularly in cases where the cancer has spread to bones or other localized sites. Common side effects seen after radiation therapy are redness on the skin, rashes, loose motions, and fatigue.

Combination Therapies: Different management approaches involve a combination of different treatment modalities, like immunotherapy in combination with radiotherapy, which has also proven to be effective in the management of metastatic renal cancer.

Surgical Therapy: Radical nephrectomy (surgical removal of the kidney) is one of the treatment approaches advised by doctors for the management of kidney cancer that has not spread outside the kidneys. During this surgical approach, the surgeon removes the following parts surgically:

1. The kidney part that has a tumor.

2. Adrenal gland (two small triangular-shaped structures present above the kidney).

3. The surrounding area involved lymph nodes.

4. Fat tissues around the organs.

Surgery usually cures kidney cancer if it has not spread outside the kidney. In cases where cancer has metastasized (spread in body parts), surgery, along with other treatment modalities like immunotherapy and chemotherapy, is recommended.

Clinical Trials: Participation in clinical trials may be an option or last approach for some patients for whom all other treatment modalities fail to treat renal cancer, as researchers are continually investigating new therapies and treatment approaches for managing metastatic renal cancers.

Conclusion

The management of metastatic renal cell carcinoma (mRCC) involves a multifaceted approach, with treatment decisions tailored to individual patient factors and tumor characteristics. Targeted therapies, including tyrosine kinase and immune checkpoint inhibitors, play a crucial role in disrupting cancer progression by targeting specific pathways involved in angiogenesis and immune evasion. As advancements in precision medicine and immunotherapy continue, the outlook for metastatic renal cell carcinoma continues to evolve, offering hope for improved patient outcomes and quality of life. Ultimately, treatment decisions should be made collaboratively between patients and their healthcare teams, considering the latest evidence-based practices and the unique circumstances of each case.