Kidney Renal Clear Cell Carcinoma (KIRC), also called conventional renal cell carcinoma, is the most prevalent form of kidney cancer in adults. The disease originates within the kidney’s filtration system, which filters waste from the blood.
The cancer begins in the lining of the proximal convoluted tubules, tiny tubes that handle the initial stage of blood filtering. The name “clear cell” comes from the appearance of the cancer cells under a microscope, where they appear pale or clear. Accounting for about 80% of cases, KIRC is often silent in its early stages.
Risk Factors and Common Symptoms
Genetic predispositions and lifestyle habits can influence the likelihood of developing KIRC. Smoking is a risk factor, as carcinogens in tobacco are filtered by the kidneys. High blood pressure can damage blood vessels within the kidneys over time. Obesity is another established risk factor, linked to hormonal changes and chronic inflammation that can promote tumor growth.
Beyond modifiable factors, genetics can play a part. Certain inherited conditions are associated with an increased risk of KIRC, most notably Von Hippel-Lindau (VHL) disease. VHL is a rare genetic disorder that causes tumors and cysts to grow in various parts of the body, including the kidneys. The VHL gene is a tumor suppressor, and when it is mutated, it can lead to the uncontrolled cell growth that characterizes clear cell carcinoma.
The presentation of KIRC symptoms has shifted over time. Historically, the disease was associated with a “classic triad” of signs: hematuria (blood in the urine), a palpable mass, and flank pain. This combination is now seen infrequently and suggests the cancer has reached an advanced stage. Many individuals with early-stage KIRC experience no symptoms at all, and a significant number of kidney tumors are discovered incidentally during imaging for unrelated medical reasons. When symptoms do appear, they can be nonspecific and include persistent fatigue, unexplained weight loss, and a fever not caused by an infection.
Diagnosis and Staging
Diagnosing KIRC begins with detailed imaging. Computed tomography (CT) scans create cross-sectional images of the kidneys, allowing doctors to identify a tumor’s size, shape, and location. Magnetic resonance imaging (MRI) may be used for additional detail about soft tissues and to check if cancer has spread into nearby blood vessels. Ultrasounds can help distinguish between solid masses and benign cysts.
While imaging provides strong evidence, a definitive diagnosis is made through a biopsy. During this procedure, a thin needle is guided into the kidney mass to extract a small tissue sample. A pathologist then examines the cells under a microscope to confirm the presence of cancer and identify its subtype. In some cases, if imaging is highly indicative of KIRC, a doctor may recommend surgery to remove the tumor without a preceding biopsy.
Once KIRC is diagnosed, the next step is to determine its stage, which describes the extent of the cancer’s growth. The TNM staging system assesses three factors: the size of the primary tumor (T), spread to nearby lymph nodes (N), and metastasis to distant parts of the body (M). In conjunction with staging, the cancer is assigned an ISUP (International Society of Urological Pathology) grade. This grade evaluates how abnormal the cancer cells appear microscopically, with a lower grade suggesting a slower-growing cancer and a higher grade indicating a more aggressive disease.
Treatment Approaches for KIRC
The treatment for KIRC is influenced by the cancer’s stage. For localized tumors confined to the kidney, surgery is the primary intervention. A partial nephrectomy, which removes the tumor with a margin of healthy tissue, is the preferred option to preserve kidney function. When a tumor is large or centrally located, a radical nephrectomy (removal of the entire kidney) may be necessary.
For individuals who are not suitable candidates for surgery or for those with very small tumors, non-surgical options are available. Thermal ablation techniques can destroy cancerous tissue. Cryoablation uses extreme cold to freeze and kill tumor cells, while radiofrequency ablation uses heat from an electrical current to achieve the same result. These minimally invasive procedures offer an alternative for managing localized disease.
When KIRC has spread beyond the kidney (metastatic disease), the approach shifts to systemic therapies, as traditional chemotherapy is not effective. Treatment relies on targeted therapies that interfere with specific pathways cancer cells use to grow and spread. One class of these drugs is VEGF (vascular endothelial growth factor) inhibitors, which block signals that tumors use to form new blood vessels.
Immunotherapy is another advancement in treating advanced KIRC, harnessing the body’s immune system to attack cancer cells. Checkpoint inhibitors are a common form of immunotherapy that blocks proteins preventing immune cells from targeting the tumor. A combination of different targeted therapies or a combination of targeted therapy and immunotherapy is often used to manage metastatic KIRC.
Prognosis and Post-Treatment Monitoring
The prognosis for KIRC is closely tied to the cancer’s stage when diagnosed. When the disease is detected at an early stage and is confined to the kidney, the outlook is favorable. The five-year survival rate for localized KIRC is high, as surgical removal of the tumor can be curative.
The outlook becomes more complex when the cancer has metastasized to distant organs. While modern treatments have improved outcomes, it is a more difficult condition to manage. The five-year survival rate for metastatic KIRC is lower, reflecting the aggressive nature of the disease once it has spread.
Following initial treatment, patients enter active surveillance to monitor for cancer recurrence. This involves regular follow-up appointments with an oncologist and imaging tests, like CT scans, at set intervals. These tests check for new tumor growth in the original cancer area or elsewhere.
This long-term monitoring is designed to detect a recurrence as early as possible. The frequency of scans and appointments is highest in the first few years after treatment and may become less frequent over time if no signs of recurrence appear. This follow-up ensures that any new developments are addressed promptly.