Annual incidence in the United States is about 73,820 cases with 14,770 deaths. Cigarette smoking accounts for 20-30% of cases. Risk is increased in acquired renal cystic disease. There are two familial forms: a rare autosomal dominant syndrome and von Hippel-Lindau disease. About 35% of pts with von Hippel-Lindau disease develop renal cancer. Incidence is also increased in those with tuberous sclerosis and polycystic kidney disease.
Most cases are sporadic; however, the most frequent chromosomal abnormality (occurs in 60%) is deletion or rearrangement of 3p21-26. The von Hippel-Lindau gene has been mapped to that region and appears to have ubiquitin ligase activities that influence regulation of speed of transcription and turnover of damaged proteins. It is unclear how lesions in the gene lead to cancer.
Five variants are recognized: clear cell tumors (75%), papillary tumors (15%), chromophobic tumors (5%), oncocytic tumors (3%), and collecting duct tumors (2%). Clear cell tumors arise from cells of the proximal convoluted tubules. Papillary tumors tend to be bilateral and multifocal and often show trisomy 7 and/or trisomy 17. Chromophobic and eosinophilic tumors less frequently have chromosomal aberrations and follow a more indolent course.
The classic triad of hematuria, flank pain, and flank mass is seen in only 10-20% of pts; hematuria (40%), flank pain (40%), palpable mass (33%), and weight loss (33%) are the most common individual symptoms. Paraneoplastic syndromes of erythrocytosis (3%), hypercalcemia (5%), and nonmetastatic hepatic dysfunction (Stauffer's syndrome) (15%) may also occur. Workup should include IV pyelography, renal ultrasonography, CT of abdomen and pelvis, chest x-ray (CXR), urinalysis, and urine cytology. Stage I is disease restricted to the kidney, stage II is disease contained within Gerota's fascia, stage III is locally invasive disease involving nodes and/or inferior vena cava, stage IV is invasion of adjacent organs or metastatic sites. Prognosis is related to stage: 66% 5-year survival for I, 64% for II, 42% for III, and 11% for IV.
| TREATMENT | ||
Renal CancerRadical nephrectomy is standard for stages I, II, and most stage III pts. Surgery may also be indicated in the setting of metastatic disease for intractable local symptoms (bleeding, pain). Response rates of 40-48% have been noted with a range of different single agents, sunitinib (50 mg/d 4 weeks out of 6), sorafenib (400 mg bid), and temsirolimus (25 mg IV weekly) and the related drug, everolimus (10 mg PO daily), the PD1 inhibitor, nivolumab and cabozantinib (60 mg PO daily), an inhibitor of MET, AXL, and the vascular endothelial growth factor receptor. Sunitinib and sorafenib are thought to be antiangiogenic through inhibition of kinases in tumor cells. Temsirolimus is an inhibitor of mTOR. Nivolumab allows activation of T cells that kill the tumor cells. Combinations of PD1 or PD-L1-directed checkpoint blockers plus axitinib, a VEGF inhibitor, appear both more frequent and durable than those obtained with sunitinib alone. About 10-15% of pts with advanced-stage disease may benefit from interleukin 2 and/or interferon α (IFN-α). Addition of bevacizumab to IFN-α improves the response rate. Some remissions are durable. Chemotherapy is of little or no benefit. |