Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, originating in the tiny tubes inside the kidney that filter waste from your blood. It accounts for roughly 90% of all kidney cancers and is often discovered by accident during imaging done for an unrelated reason. Between 37% and 61% of new cases are now found incidentally on CT scans or ultrasounds, which means many people learn they have it before experiencing any symptoms at all.
Where It Starts
Your kidneys contain millions of microscopic filtering units called nephrons. Each nephron has a small tube, the proximal tubule, lined with specialized cells that reabsorb nutrients and water from the fluid that will eventually become urine. RCC develops when the DNA in these cells accumulates enough damage to trigger uncontrolled growth. The most important genetic event in the majority of cases involves a gene called VHL, which normally acts as a brake on tumor growth. When that brake fails, cells begin dividing without the usual checks.
Main Subtypes
Not all renal cell carcinomas behave the same way. The three main subtypes differ in how they look under a microscope, how aggressively they grow, and how they respond to treatment.
- Clear cell RCC makes up 70% to 80% of all cases. It gets its name from the pale, clear appearance of its cells. This subtype is most closely linked to VHL gene mutations and tends to be the most responsive to modern immunotherapy.
- Papillary RCC is the second most common subtype. It grows in finger-like projections and is often less aggressive than clear cell, though some variants can behave more aggressively.
- Chromophobe RCC is rarer and generally carries a better prognosis than the other two. It originates from a different part of the nephron’s collecting system.
Several other rare subtypes exist, including medullary RCC, collecting duct carcinoma, and translocation-associated RCC, but together these account for a small minority of cases.
Symptoms and How It’s Found
The classic trio of symptoms taught in medical textbooks is flank pain, blood in the urine, and a mass you can feel in the abdomen. In practice, fewer than 10% of people show up with all three. Most people diagnosed today had no kidney-related symptoms. Their tumor showed up on an abdominal CT or ultrasound ordered for something else entirely, like back pain or a gallbladder evaluation.
When symptoms do appear, blood in the urine (which can be visible or only detectable on a lab test) is the most common. Some people notice a dull ache on one side of the back, unexplained weight loss, fatigue, or fevers that come and go without an obvious infection. RCC is sometimes called “the great masquerader” because it can produce a wide range of effects throughout the body that seem unrelated to the kidneys.
Paraneoplastic Effects
Roughly 10% to 40% of people with RCC develop what are called paraneoplastic syndromes, conditions caused not by the tumor physically pressing on something but by substances the tumor releases into the bloodstream. This is unusually common compared to most other cancers.
The most frequent is high blood calcium, affecting 13% to 20% of RCC patients. It can cause excessive thirst, frequent urination, constipation, confusion, and fatigue. Another well-known effect is Stauffer syndrome, seen in 3% to 20% of patients, where liver enzyme levels become abnormal even though the cancer hasn’t spread to the liver. These abnormalities typically resolve once the kidney tumor is removed but can return if the cancer recurs. Other paraneoplastic effects include high blood pressure, abnormal blood counts (either too many or too few red blood cells), and changes in blood sugar regulation.
Risk Factors
Three modifiable risk factors dominate: smoking, obesity, and high blood pressure. Together, these may account for roughly half of all RCC cases in the United States. Smoking roughly doubles the risk, and the risk drops gradually after quitting. Excess body weight is thought to promote kidney cancer through chronic inflammation and hormonal changes, particularly elevated insulin and related growth factors. High blood pressure damages the delicate blood vessels in the kidney over time, and the risk appears to increase with the severity of hypertension.
Most RCC occurs sporadically, meaning there’s no inherited gene driving it. However, several hereditary conditions significantly raise the risk. Von Hippel-Lindau syndrome is the best known, caused by an inherited mutation in the VHL gene. People with this condition can develop kidney tumors at a younger age, often in both kidneys. Other inherited syndromes involve mutations in genes like MET and FH, each linked to specific subtypes. Having a first-degree relative with kidney cancer also modestly increases your risk, even without a known genetic syndrome, suggesting that lower-penetrance susceptibility genes play a role.
Staging and What It Means
Staging describes how far the cancer has grown and is the single biggest factor in determining treatment options and outlook. The system is based on tumor size and whether the cancer has spread beyond the kidney.
- Stage I: The tumor is 7 cm or smaller (roughly the size of a tennis ball or less) and is entirely contained within the kidney. This is further split into T1a (4 cm or smaller) and T1b (between 4 and 7 cm).
- Stage II: The tumor is larger than 7 cm but still confined to the kidney.
- Stage III: The tumor has grown into major veins near the kidney or into the fatty tissue surrounding it, but hasn’t pushed past the outer envelope of tissue (called Gerota’s fascia) that wraps around the kidney. In some cases, the tumor extends into the large vein that carries blood back to the heart.
- Stage IV: The tumor has broken through Gerota’s fascia, invaded the adrenal gland sitting on top of the kidney, or spread to lymph nodes or distant organs like the lungs, bones, or brain.
Survival by Stage
The five-year relative survival rate varies dramatically depending on how far the cancer has spread at diagnosis. For localized RCC (confined to the kidney), the five-year survival rate is 93.3%. When cancer has spread to nearby lymph nodes or tissues (regional stage), it drops to 76.4%. For distant-stage disease, where the cancer has reached other organs, the five-year survival rate is 19.1%. These numbers come from cases diagnosed between 2015 and 2021, and newer treatments introduced in recent years may improve outcomes for advanced disease beyond what these statistics reflect.
Surgical Treatment
Surgery remains the primary treatment for RCC that hasn’t spread to distant sites. The key decision is whether to remove the entire kidney (radical nephrectomy) or just the tumor and a margin of healthy tissue (partial nephrectomy).
Current guidelines favor partial nephrectomy whenever it’s technically feasible, regardless of tumor size. The rationale is straightforward: preserving as much healthy kidney tissue as possible protects long-term kidney function and lowers the risk of developing chronic kidney disease later in life. For tumors 4 cm or smaller, partial nephrectomy is strongly recommended. For tumors between 4 and 7 cm, it’s still preferred when the tumor’s location allows safe removal without compromising the remaining kidney. Radical nephrectomy becomes more common for very large tumors, those in difficult locations, or those that have grown into surrounding structures.
Most kidney surgery today is performed using minimally invasive techniques, either laparoscopic or robot-assisted, which typically means shorter hospital stays and faster recovery compared to open surgery.
Treatment for Advanced Disease
When RCC has spread beyond the kidney, the treatment landscape has changed dramatically over the past several years. The current standard for metastatic clear cell RCC combines two types of therapy: an immune checkpoint inhibitor, which helps your immune system recognize and attack cancer cells, paired with either a second checkpoint inhibitor or a targeted drug that blocks the blood vessel growth tumors need to survive.
These combination regimens are now approved for use across all risk categories. For patients with favorable-risk disease (slower-growing cancers with fewer symptoms), a targeted drug alone remains a reasonable option. The choice between regimens depends on factors like the number and location of metastatic sites, overall health, and the specific risk profile of the cancer. For example, patients with bone metastases appear to benefit more from the combination of a checkpoint inhibitor with a targeted drug, while the calculus can differ for metastases in other locations.
RCC is notably resistant to traditional chemotherapy, which is why these immune-based and targeted approaches have become the backbone of treatment. Radiation therapy plays a limited role but can be useful for managing symptoms from specific metastatic sites, particularly in the brain or bones.