Renal Cancer

Epidemiology and Etiology

RCC is estimated to result in approximately 74,750 cases and 14,830 deaths in the US in 2020.¹ It is more commonly diagnosed in men and the risk increases with age.

Pathology

RCC is a malignancy of the renal parenchyma. Clear cell RCC is the most common subtype (80%-85%), followed by papillary types 1 and 2 (15%) and chromophobe (5%).

Clinical Presentation

Most patients in the US are diagnosed by incidental findings on CT scan. Symptoms may occur due to local tumor growth, metastatic disease, or paraneoplastic syndrome. The most common symptoms include anemia, hematuria, cachexia, and fever. The classic triad of flank pain, hematuria, and a palpable mass is uncommonly seen. Paraneoplastic syndromes include hypercalcemia, erythrocytosis, and Stauffer syndrome, which is defined by the presence of nonmetastatic hepatic dysfunction with elevated alkaline phosphatase, serum bilirubin and transaminases, and a prolonged prothrombin time.

Diagnostic Testing

The initial workup should include CT of the abdomen and pelvis, but ideally will also include CT of the chest. MRI may be used to evaluate for involvement of the inferior vena cava or in patients that cannot receive contrast due to allergy or moderate renal insufficiency. The probability of RCC increases with the diameter of the lesion and with enhancement greater than 15 Hounsfield units by CT scan. The role of PET imaging is limited due to the high background activity from the normal renal excretion of fluorodeoxyglucose (FDG). Since most brain and bone metastases are symptomatic, bone scan and brain MRI are performed only when clinically indicated rather than routinely. Centrally located lesions may represent urothelial carcinoma, with further evaluation indicated as this is treated as bladder cancer.

Staging

TNM: T1 (lt;7 cm), T2 (7-10 cm), T3 (extends into veins or perinephric tissues), T4 (extends beyond Gerota fascia), N0 (no lymph node involvement), N1 (involved lymph nodes), Ml (distant metastasis). Stage: I (T1N0M0), II (T2N0M0), III (T1-2N1M0 or T3N0-1M0), IV (T4 or M1).

TREATMENT

• Stage I (local): The treatment of choice for patients with localized disease is surgical resection including either radical or partial (nephron-sparing) nephrectomy.

• Stage II-III (locally advanced): The treatment of choice is radical nephrectomy, which involves removal of the Gerota fascia, perirenal fat, regional lymph nodes, and ipsilateral adrenal gland, although select patients may be considered for partial nephrectomy.

• Stage IV (metastatic): The choice of therapy typically depends on the histology, patient risk stratification, and disease burden. One such risk stratification tool is the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model which stratifies RCC into low-, intermediate-, or high-risk categories, based on the presence of 0, 1-3, or gt;3 of the following risk factors: (1) Karnofsky performance status (KPS) lt;80%, (2) time from diagnosis to treatment lt;1 year, (3) hemoglobin concentration less than the lower limit of normal (LLN), (4) serum calcium greater than the upper limit of normal (ULN), (5) neutrophil count greater than the ULN, and (6) platelet count greater than the ULN. Treatment options for patients with clear cell histology include pembrolizumab in combination with axitinib or lenvatinib and the combination of nivolumab with cabozantinib. Additional options or patients with intermediate or poor risk include nivolumab plus ipilimumab and single-agent cabozantinib. Subsequent treatments depend on prior regimens used and include ICIs, multitargeted TKIs, and everolimus. Select patients may benefit from cytoreductive nephrectomy.²⁰