Renal Cell Carcinoma: Causes, Symptoms, Treatment and Prognosis — Overview, Diagnosis & Treatment Options | MyMedicPlus

Renal cell carcinoma (RCC) accounts for approximately 90% of kidney cancers, with clear cell RCC (ccRCC) the most common subtype (~70%). Approximately 431,000 new cases occur worldwide annually. Incidence has risen due to incidental detection on cross-sectional imaging. The male-to-female ratio is approximately 2:1.

Tobacco smoking doubles risk; obesity, hypertension, and trichloroethylene exposure are established risk factors. Hereditary syndromes: VHL syndrome (ccRCC), hereditary papillary RCC (MET mutation), Birt-Hogg-Dube syndrome (FLCN mutation), and hereditary leiomyomatosis and RCC syndrome (FH mutation) together account for approximately 3-5% of RCC.

The classic triad of hematuria, flank pain, and palpable mass is present in less than 10% of patients. Most RCC is now discovered incidentally. Paraneoplastic syndromes include polycythemia, hypercalcemia, hypertension, and Stauffer syndrome (non-metastatic hepatic dysfunction). Constitutional symptoms (weight loss, fever, night sweats) occur in metastatic disease.

Contrast-enhanced CT urography is the standard imaging study. Biopsy is recommended for non-surgical candidates or ambiguous lesions. CT TNM staging. Clear cell RCC: VHL mutation analysis, PD-L1 expression. Germline genetic testing for hereditary syndromes. IMDC (International Metastatic RCC Database Consortium) prognostic score guides first-line systemic therapy selection.

Localized RCC: partial nephrectomy preferred for T1-T2 tumors (nephron-sparing); radical nephrectomy for larger or complex tumors. Thermal ablation (RFA, cryotherapy) for small tumors in poor surgical candidates. Metastatic ccRCC: nivolumab plus ipilimumab or pembrolizumab plus axitinib/lenvatinib as first-line doublets. Belzutifan (HIF-2α inhibitor) for VHL disease. Cabozantinib or everolimus for subsequent lines.

Stage I: 5-year survival over 90%. Stage II: approximately 75%. Stage III: approximately 53%. Stage IV: approximately 12-20% (improved from historical 5% with sunitinib monotherapy due to immunotherapy combinations). Modern IO/TKI doublets have transformed metastatic RCC outcomes with sustained responses in some patients.