The treatment of kidney cancer, most commonly Renal Cell Carcinoma (RCC), involves a complex decision-making process based on the cancer’s stage, the tumor’s characteristics, and the patient’s overall health status. Because kidney cancer often resists traditional chemotherapy, treatment strategies typically focus on local control of the tumor or systemic therapies that target specific molecular pathways or engage the body’s immune system. The general goal of care is either to achieve a cure for localized disease or to control the cancer’s growth and manage symptoms for advanced disease. Modern approaches are increasingly personalized, moving away from a one-size-fits-all model to offer the most effective and least toxic option for each individual.
Local Tumor Control: Surgery and Ablation
Surgery remains the primary treatment for kidney cancer that is confined to the organ. The two main surgical procedures are partial and radical nephrectomy. A partial nephrectomy, also known as nephron-sparing surgery, removes only the tumor along with a small margin of surrounding healthy tissue, leaving the rest of the kidney intact. This technique is now the preferred option whenever technically feasible, especially for smaller tumors, as it helps preserve long-term kidney function.
A radical nephrectomy involves removing the entire kidney, often along with the adrenal gland and surrounding tissue. This more extensive surgery is reserved for larger or centrally located tumors, or when the tumor has invaded nearby structures. Both types of surgery can often be performed through minimally invasive techniques, such as laparoscopy or robotic-assisted surgery. Minimally invasive approaches generally lead to less pain and a faster recovery time compared to traditional open surgery.
For patients who are not healthy enough to undergo major surgery or have small, localized tumors, minimally invasive ablation techniques offer an alternative. These procedures destroy the tumor in place without needing to remove the tissue. Radiofrequency ablation (RFA) uses heat generated by radio waves to kill cancer cells, while cryoablation uses extreme cold delivered via a probe inserted into the tumor.
Ablation is particularly useful for tumors less than four centimeters in diameter and is guided by imaging like ultrasound or CT scans. The procedure ensures precise targeting of the tumor. These non-surgical options typically involve shorter hospital stays and quicker return to normal activity.
Targeting Cancer Growth: Molecular Therapies
Targeted therapies block the signals cancer cells rely on, unlike traditional chemotherapy. A major focus in kidney cancer is blocking the process of angiogenesis, which is the formation of new blood vessels that tumors need to grow and metastasize.
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) block signals from the VEGF pathway. Since clear cell RCC, the most common type, is highly vascularized, inhibiting this pathway effectively starves the tumor of its blood supply. Examples of these drugs include sunitinib, pazopanib, and axitinib, which are often used as initial treatments for advanced disease.
Another class of targeted agents are the mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and temsirolimus. The mTOR pathway is a central regulator of cell growth, proliferation, and survival, and it is often overactive in kidney cancer cells. These inhibitors work downstream of the VEGF pathway and are typically used for advanced disease, sometimes after a patient’s cancer has progressed on a TKI.
The selection of a specific TKI or mTOR inhibitor is guided by factors like the patient’s overall health, the tumor’s specific characteristics, and previous treatments received. Combinations of targeted therapies or targeted therapy with immunotherapy are also becoming common strategies in the first-line setting.
Harnessing the Immune System: Immunotherapy
Immunotherapy represents a significant advancement in the treatment of kidney cancer, leveraging the body’s own defenses to fight the disease. Kidney cancer is one of the more immunogenic tumor types, meaning it is often recognized by the immune system. The goal of immunotherapy is not to attack the cancer directly, but to stimulate the patient’s T-cells to recognize and destroy the malignant cells.
The most widely used form of immunotherapy involves immune checkpoint inhibitors, specifically those that target the PD-1/PD-L1 pathway. Cancer cells often express PD-L1, which binds to the PD-1 receptor on T-cells, putting a “brake” on the immune response. Drugs like nivolumab and pembrolizumab block this interaction, releasing the brakes and allowing the immune system to attack the tumor.
These checkpoint inhibitors are now a standard of care for many patients with advanced kidney cancer, often used alone or in combination with a TKI or another checkpoint inhibitor, such as an anti-CTLA-4 antibody. Older forms of immunotherapy, such as high-dose interleukin-2 (IL-2), were associated with severe toxicities. The newer checkpoint inhibitors offer a more favorable side-effect profile and are effective for a much larger group of patients.
Checkpoint inhibitors are also used in the adjuvant setting (after surgery) for patients with a high risk of recurrence. Activating the immune system post-surgery aims to eliminate any microscopic residual disease, reducing the chance of the cancer returning. Ongoing research continues to explore new combinations and novel targets to improve the depth and duration of these immune responses.
Contextual Treatments: Radiation and Active Surveillance
Radiation therapy was historically considered less effective for kidney cancer, but modern technology has redefined its role. Conventional external beam radiation therapy is rarely used as a primary curative treatment for a localized tumor. Its primary use is palliative, relieving pain or managing symptoms caused by metastases (e.g., spread to the bone or brain).
Recent advancements, particularly Stereotactic Body Radiation Therapy (SBRT), allow for the precise delivery of very high doses of radiation in fewer treatment sessions. SBRT has demonstrated high local control rates for both the primary tumor in patients who are not surgical candidates and for limited metastatic sites. This focused approach can sometimes be used to delay the need for systemic therapy in patients with a small number of metastatic spots.
Active surveillance is a non-interventional strategy reserved for select patients with small, slow-growing kidney tumors, involving regular monitoring with imaging scans and blood tests. It is recommended for older patients or those with significant health issues where the risks of surgery or ablation outweigh the threat posed by the small tumor.
Treatment is only initiated if the tumor shows significant growth or the patient develops concerning symptoms. While chemotherapy is the mainstay for many other cancers, it is rarely effective for typical clear cell RCC and is reserved for rare, non-clear cell subtypes or specific advanced settings. The individual decision for active surveillance or a palliative approach depends on a careful assessment of the tumor’s biology and the patient’s quality of life considerations.