Kidney Cancer

“Kidney cancer” is a broad term. In adults, renal cell carcinoma is the most common malignant tumor arising from the kidney itself. It develops from cells lining the renal tubules.

Other cancers can also arise in or around the kidney, including urothelial carcinoma of the renal pelvis and Wilms tumor in children, but these are biologically different diseases and are treated differently. This page focuses on adult renal cell carcinoma.

Major histologic subtypes include clear cell RCC, papillary RCC, chromophobe RCC, and several less common forms.

Clear cell RCC is the most common subtype and currently has the strongest evidence base for immunotherapy, targeted therapy, and adjuvant systemic treatment.

Most people with RCC do not have a single identifiable cause.

Recognized risk factors include smoking, obesity, high blood pressure, increasing age, certain occupational or environmental exposures, chronic kidney disease, family history, and inherited kidney cancer syndromes.

Inherited RCC accounts for a minority of cases, but genetic counseling and testing may be considered in patients who develop kidney cancer at a young age, have bilateral or multifocal tumors, or have a strong family history.

Inherited syndromes associated with RCC include Von Hippel-Lindau disease, hereditary papillary renal carcinoma, Birt-Hogg-Dubé syndrome, and hereditary leiomyomatosis and renal cell cancer.

Early kidney cancer often causes no symptoms and is frequently discovered incidentally during imaging performed for another reason.

Possible symptoms include blood in the urine, persistent pain in the side or back, an abdominal or flank mass, unexplained weight loss, fatigue, fever, anemia, and loss of appetite.

The classic combination of hematuria, flank pain, and an abdominal mass is traditionally called the “renal cancer triad.” However, all three symptoms occurring together is uncommon today and usually suggests more advanced disease rather than early cancer.

RCC can also cause paraneoplastic effects such as high blood pressure, high calcium levels, anemia, or an increased red blood cell count.

Metastatic disease may cause symptoms related to the affected organs, including cough, shortness of breath, bone pain, fractures, or neurologic symptoms.

Imaging is central to the diagnosis of RCC.

Contrast-enhanced CT is one of the most important tests for evaluating a renal mass. It helps define tumor size and location, local extension, renal vein or inferior vena cava involvement, lymph nodes, and distant metastases.

MRI may provide additional detail in selected patients, particularly when venous tumor thrombus or local invasion needs further evaluation or when contrast-enhanced CT is not appropriate.

Ultrasound can detect many renal masses but is generally not sufficient by itself to characterize and stage RCC.

Laboratory testing may include a complete blood count, kidney and liver function tests, and calcium levels. There is currently no blood or urine tumor marker that can reliably diagnose RCC on its own.

Renal mass biopsy is used selectively. It may not be necessary before surgery when imaging is highly suspicious and surgery is already planned. However, biopsy can be valuable before active surveillance, ablation, systemic therapy, or when imaging findings are uncertain.

Histology and Staging

Treatment depends not only on TNM stage but also on histologic subtype and tumor grade.

TNM staging evaluates the size and local extent of the primary tumor, regional lymph node involvement, and distant metastases.

Patients are then grouped into stages I through IV.

In localized RCC, recurrence risk is further influenced by factors such as tumor grade, necrosis, and sarcomatoid features. In metastatic RCC, prognostic models such as the IMDC criteria may also help guide treatment planning.

Localized Renal Cell Carcinoma

Surgery remains one of the main treatments for localized RCC.

For appropriately selected small and localized tumors, partial nephrectomy is often preferred because it can provide cancer control comparable with radical nephrectomy while preserving more kidney function.

Radical nephrectomy may be necessary for larger or more complex tumors or when partial nephrectomy cannot safely achieve adequate cancer control.

Removal of the adrenal gland or extensive lymph node dissection is not automatically required for every patient.

Active Surveillance and Ablative Therapy for Small Renal Masses

The older statement that ablation remains purely experimental is no longer accurate.

Active surveillance may be appropriate for selected patients with small renal masses, particularly older adults, patients with substantial medical conditions, or tumors that appear to be growing slowly.

Active surveillance means scheduled imaging and clinical assessment rather than simply leaving the tumor untreated.

For selected patients who are not good surgical candidates, cryoablation and other thermal ablation techniques are established treatment options.

Postoperative Adjuvant Therapy

The statement that there is no established adjuvant treatment after RCC surgery is now outdated.

Most patients with lower-risk disease still undergo surveillance alone after surgery.

However, adjuvant immunotherapy is now supported by evidence for selected patients with clear cell RCC at higher risk of recurrence. Current EAU guidance strongly recommends considering adjuvant pembrolizumab for patients meeting the KEYNOTE-564 risk criteria and notes improvement in both disease-free and overall survival.

In June 2026, the U.S. FDA also approved belzutifan plus pembrolizumab as adjuvant treatment for adults with RCC containing a clear cell component who are at intermediate-high or high risk of recurrence after nephrectomy. Availability varies by country.

Advanced or Metastatic Renal Cell Carcinoma

Treatment of advanced RCC has changed substantially. Conventional chemotherapy has only a limited role in the most common clear cell subtype, while immunotherapy and targeted therapy now form the backbone of treatment.

Common first-line combinations for metastatic clear cell RCC include pembrolizumab plus axitinib, nivolumab plus cabozantinib, pembrolizumab plus lenvatinib, and nivolumab plus ipilimumab.

The choice depends on factors such as IMDC risk group, tumor burden, symptoms, other health conditions, prior therapy, and drug availability.

Later-line treatment may include VEGF-targeted therapies such as cabozantinib and, in selected previously treated patients, the HIF-2α inhibitor belzutifan.

Cytoreductive Nephrectomy

Cytoreductive nephrectomy is no longer routinely recommended for every patient whose primary kidney tumor is technically removable.

In the modern immunotherapy and targeted-therapy era, patients who need prompt systemic treatment often start with drug therapy first and may be reassessed for surgery later if the disease responds.

Surgery may still be considered in carefully selected patients, such as those with significant symptoms from the primary tumor, limited metastatic disease that can potentially be completely removed, or favorable overall clinical circumstances.

Current EAU guidance emphasizes that cytoreductive nephrectomy is palliative for most patients with metastatic RCC and does not replace systemic treatment.