Kidney Cancer (Renal Cell Carcinoma): Symptoms, Staging, and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Kidney cancer comprises several histological subtypes, of which renal cell carcinoma (RCC) represents approximately 90% of cases. Clear cell RCC is the most common subtype (70-80%). Approximately 76,000 new US cases are diagnosed annually, with approximately 14,000 deaths. Incidental discovery on cross-sectional imaging has increased early-stage detection. Incidence is rising, associated with increased rates of obesity, hypertension, and diabetic kidney disease. RCC is 2 times more common in men than women.

Smoking doubles RCC risk. Obesity, hypertension, and chronic kidney disease each independently increase risk. Hereditary syndromes: VHL disease (clear cell RCC), hereditary papillary RCC (MET mutation), Birt-Hogg-Dube syndrome (FLCN mutation, chromophobe and oncocytoma), hereditary leiomyomatosis and RCC (FH mutation, aggressive papillary Type 2). Occupational exposures to cadmium, asbestos, and trichloroethylene confer additional risk. Analgesic nephropathy from prolonged NSAID or phenacetin use increases renal pelvis transitional cell carcinoma risk more than RCC.

The classic triad of hematuria, flank pain, and palpable abdominal mass occurs in fewer than 10% of RCC patients. Most tumors are now detected incidentally on imaging performed for other reasons. Paraneoplastic syndromes are more common in RCC than most other cancers: hypertension (renin secretion), polycythemia (erythropoietin), hypercalcemia (PTHrP), Stauffer syndrome (elevated liver enzymes without hepatic metastases), and amyloidosis. Metastatic symptoms include cough (pulmonary), bone pain (skeletal), headaches (CNS), and paraneoplastic fever.

CT urography (renal mass protocol with pre-contrast, arterial, venous, and delayed phases) is the standard imaging modality. The Bosniak classification guides management of cystic renal masses (I-V, with IV and V requiring surgery). MRI is used for CT-indeterminate lesions or to assess venous thrombus extent. Percutaneous needle biopsy is appropriate for small (less than 3 cm) indeterminate lesions or suspected metastatic disease. Germline testing (VHL, FLCN, FH, MET) is recommended for bilateral or multifocal tumors, young patients, or positive family history. AJCC 8th edition TNM staging is used; IMDC score stratifies metastatic patients.

Localized RCC: partial nephrectomy (preferred for tumors up to 7 cm and amenable to nephron-sparing) or radical nephrectomy; active surveillance for small (less than 3 cm) lesions in older patients; thermal ablation (RFA or cryoablation) for small tumors in non-surgical candidates. Adjuvant pembrolizumab (KEYNOTE-564) for Stage II-III high-risk RCC reduces recurrence. Metastatic clear cell RCC: nivolumab plus ipilimumab (intermediate/poor risk); axitinib plus pembrolizumab, cabozantinib plus nivolumab, or lenvatinib plus pembrolizumab across risk groups; belzutifan or cabozantinib for VHL-mutant or subsequent lines. Non-clear cell: clinical trial enrollment recommended.

Five-year survival by AJCC stage: Stage I approximately 81%, Stage II approximately 74%, Stage III approximately 53%, Stage IV approximately 8-12% (historical). With modern immunotherapy combinations for metastatic RCC, 5-year OS has improved substantially: approximately 42% for CheckMate 214 (nivolumab plus ipilimumab) for intermediate and poor risk patients. VHL-mutant and IMDC favorable-risk patients have the best outcomes. Sarcomatoid differentiation (present in approximately 20% of RCC) predicts aggressive behavior and poor prognosis but specifically high response rate to nivolumab plus ipilimumab.

Smoking cessation reduces RCC risk by approximately 30% within 5 years. Blood pressure control with antihypertensive therapy and weight management reduce modifiable risk factors. Patients with hereditary RCC syndromes (VHL, FLCN, FH, MET) require annual renal imaging surveillance starting in early adulthood. Belzutifan treats VHL disease-associated RCC and can delay surgical intervention. Avoidance of trichloroethylene, cadmium, and asbestos in occupational settings reduces exposure-related risk. No general population screening is recommended for RCC.