What is the prognosis of clear cell renal cell carcinoma (CCRCC)?

Updated: Mar 11, 2019
  • Author: Ronald J Cohen, MB, BCh, PhD, FRCPA, FFPATH; Chief Editor: Liang Cheng, MD  more...
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Patients with clear cell renal cell carcinoma (CCRCC) tend to have a worse prognosis than patients with other histologic subtypes of RCC, with 5-year disease-specific survival rates of 50-69%, compared with 67-87% for papillary RCC and 78-87% for chRCC. [7, 8, 46, 100] However, analysis of 1000 patients showed very similar 5-year disease-specific survival rates for CCRCC (10.5%) and papillary RCC (10.3%) once metastatic disease was present. [5]

Multivariate analyses indicate that histologic RCC subtype has no significant independent value for predicting cancer-specific survival because prognosis is primarily dependent upon TNM stage and Fuhrman nuclear grade. [5, 8, 40] Multivariate analysis specifically of CCRCC cases shows that in addition to the 3 separate components of tumor staging (T, N and M stage), other significant independent predictors of poor prognosis are nuclear grade, tumor size, and the presence of histologic necrosis or sarcomatoid differentiation. [39, 46, 47, 24]

Rhabdoid differentiation is also observed in CCRCC and seems to impart a poor outcome similar to sarcomatoid change [51, 53, 54] ; however, this factor has not yet been tested in predictive models. Interestingly, histological necrosis is seen more commonly in papillary RCC (39-46%, compared with 28-37% for CCRCC) but is not a significant predictor of poor prognosis for papillary RCC, even in univariate analyses. [7, 46, 47]

Assessment of molecular pathways may further contribute to predicting ultimate prognosis. The association between loss of chromosome 14q and differential expression of HIFα1 on clinical outcome in patients with nonmetastatic CCRC may advocate these as molecular markers of poor prognosis. [92, 93] In addition, recent data related to mTor and hypoxia-induced pathways in CCRCC appear encouraging and may provide improved prognostication for the individual patient. [101]

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