Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up.

RCC is a male-predominant (2:1) disease with a typical presentation in the sixth and seventh decades of life (median age 60 years). Patients with RCC may present with local or systemic symptoms, although most presentations are incidental owing to the widespread use of abdominal imaging. Local signs and symptoms include hematuria, flank pain or a palpable abdominal mass, all of which imply negative prognostic features. Systemic symptoms may be due to metastases or paraneoplastic phenomena, such as hypercalcemia, unexplained fever, erythrocytosis or wasting syndromes. Prevalent use of ultrasonography and cross-sectional imaging is now associated with incidental detection of many asymptomatic renal tumors and there has been a stage migration with less presentation of synchronous metastatic disease. Diagnosis is usually suggested by ultrasonography, and confirmed by CT scan, which allows for assessment for local invasiveness, lymph node involvement or other metastases. Pathology from either the primary tumor or a metastatic site confirms the diagnosis and allows pathological classification. Most common is clear cell cancer, followed by papillary cancer (either type 1 or 2), and then rare histologies, such as chromophobe, collecting duct, medullary and unclassified. A four-tiered grading system (Fuhrman system) based on nuclear morphology is a significant prognostic factor in clear cell RCC. Sarcomatoid differentiation is not a distinct histological subtype, but is a growth pattern that can occur across all subtypes suggesting an aggressive disease course. Risk assessment models have been created for use in eligibility, stratification in randomization for phase III trials and assessment of outcome. A model derived from data at Memorial Sloan-Kettering Cancer Center (MSKCC, New York, NY) and later validated by investigators at the Cleveland Clinic Foundation (Cleveland, OH) is used widely. In this model, five variables are considered risk factors for short survival: low Karnofsky performance status (<70), elevated lactate dehydrogenase, low serum hemoglobin, elevated ‘corrected’ serum calcium and time from initial RCC diagnosis to start of therapy of <1 year. Patients are divided into three groups based upon pretreatment features: favorable (no risk factors, median survival 30 months); intermediate (one or two risk factors, median survival 14 months) or poor (three or more risk factors, median survival 6 months). The TNM 2002 staging system should be used (Table 1).