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Key Clinical Updates in Renal Cell Carcinoma

For patients with von Hippel-Lindau disease and renal cell carcinoma, belzutifan, a HIF2a inhibitor, leads to dramatic size reductions in both renal and non-renal neoplasms and offers a new treatment option.

Pembrolizumab is FDA-approved for adjuvant treatment after surgical resection of renal cell carcinoma in patients at high risk for disease recurrence.

The SURTIME randomized trial compared immediate versus deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with sunitinib and showed an overall survival advantage with the deferred approach. This may serve to identify patients who respond the best to systemic therapy prior to undergoing removal of the primary tumor.

Bex A et al. JAMA Oncol. [PMID: 30543350]

Jonasch E et al. N Engl J Med. [PMID: 34818478]

Rini BI et al; KEYNOTE-426 Investigators. N Engl J Med. [PMID: 30779529]


  • Gross or microscopic hematuria.

  • Flank pain or mass in some patients.

  • Systemic symptoms such as fever, weight loss may be prominent.

  • Solid renal mass on imaging.


Kidney (renal cell) and renal pelvis carcinomas account for 3.8% of all adult cancers. In 2022 in the United States, it is estimated that approximately 79,000 cases of renal cell carcinoma will be diagnosed and 13,920 deaths will result. Renal cell carcinoma has a peak incidence in the sixth decade of life and a male-to-female ratio of 2:1. It may be associated with several paraneoplastic syndromes (see eTable 39–1).

Risk factors include physical inactivity, obesity, and diabetes mellitus. Cigarette smoking is the only known significant environmental risk factor. Familial causes of renal cell carcinoma have been identified (von Hippel-Lindau syndrome, hereditary papillary renal cell carcinoma, hereditary leiomyoma-renal cell carcinoma, and Birt-Hogg-Dubé syndrome). There is an association with dialysis-related acquired cystic disease and specific genetic aberrations (eg, Xp11.2 translocation). But sporadic carcinomas are far more common.

Renal cell carcinoma originates from the proximal tubule cells. Various histologic cell types are recognized (clear cell, papillary, chromophobe, collecting duct, and sarcomatoid).


A. Symptoms and Signs

Historically, 60% of patients presented with gross or microscopic hematuria. Flank pain or an abdominal mass was detected in approximately 30% of cases. The triad of flank pain, hematuria, and mass, found in only 10% of patients, is often a sign of advanced disease. Fever can occur as a paraneoplastic symptom (see eTable 39–1). Symptoms of metastatic disease (cough, bone pain) occur in 20–30% of patients at presentation. Due to the widespread use of ultrasound and cross-sectional imaging, renal tumors are frequently detected incidentally in individuals with no urologic symptoms. Consequently, there has been profound stage migration toward lower stages of disease over the last 20 years with increased detection of small, indolent tumors. Population mortality rates have remained relatively stable.

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