February 23, 2007

Significance Of Macroscopic Tumor Necrosis As A Prognostic Indicator For Renal Cell Carcinoma

UroToday.com- The observation that renal cell carcinoma (RCC) tumors can develop areas of necrosis that are apparent on radiographic, gross, and microscopic examination is not a new finding. Much has been made of this observation, although the mechanism by which it occurs remains unknown. Rapid tumor growth that outgrows it's blood supply, immunologic responses, and deficient angiogenesis have been offered as possible explanations, but the true mechanism remains a mystery. Previous investigators have correlated the presence of tumor necrosis to outcome, although the definition and method of detection of necrosis has been variable among studies. Here Lee and colleagues correlate the presence of macroscopic necrosis, defined as the presence of greater than 10% necrosis identified on gross specimen examination, with outcome in patients with RCC.

The authors examined the tumor specimens of 485 patients with RCC who had surgery over a 10 year period. They found that 27% of patients had evidence of tumor necrosis, and that the presence of tumor necrosis was associated with increased tumor size, increased tumor grade, increased local tumor stage, and increased likelihood of metastatic disease (M1 or N+) (p<0.001). Furthermore, macroscopic tumor necrosis was more likely to be associated with the presence of microvascular invasion (p=0.026), sarcomatoid dedifferentiation (p=0.002), anemia, hypercalcemia, and elevated levels of alkaline phosphatase (p<0.001). The authors found that necrosis was only predictive in clear cell histology but not in not in papillary and other non-conventional histologies. In patients without metastatic disease, the presence of macroscopic necrosis was associated a significantly better progression free and disease specific survival (DSS) (p<0.0001). The 5 and 10 year DSS for patients without necrosis was 92% and 84.1% respectively, versus 79.3% and 59.3% respectively for those without evidence of necrosis. In their multivariate analysis, the authors found that macroscopic necrosis, in addition to T stage, grade, and tumor size were independent predictors of DSS in patients without metastatic disease (p=0.004).

This study confirms that necrotic death of an RCC tumor, whether identified at the radiographic, macroscopic, or microscopic level, is associated with a worse prognosis. Further understanding into the pathogenesis of this observation may provide insight into the mechanism of tumor progression and metastasis.

Lee SE, Byun SS, Oh JK, Lee SC, Chang IH, Choe G, Hong SK
J Urol 176(4): 1332-1338, 2006.

Reviewed by UroToday.com Medical Editor Christopher G. Wood

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