Sarcomatoid differentiation

Sarcomatoid differentiation is one of the most reliable indications of an aggressive tumor. In a review of 2,381 RCC cases at Mayo, sarcomatoid differentiation was present in 5%. Mean duration of survival for patients with this adverse pathologic feature was 1.4 years. Sarcomatoid features were an independent predictor of RCC death regardless of histologic subtype, stage, size, and necrosis (Am J Surg Pathol. 2004;28:435-441).

 

Prognostic algorithms

Outcome prediction models and algorithms integrate many of these findings and assist the clinician in important ways. Algorithms provide a foundation for risk stratification, patient counseling, assessment of treatment efficacy, optimal trial design, and development of surveillance programs.

 

Mayo researchers have developed algorithms to predict outcomes in patients with clear cell RCC. One of these algorithms is SSIGN (Stage, SIze, Grade, and Necrosis). SSIGN scoring can predict survival among patients with clear cell RCC treated with radical nephrectomy. In a multivariate analysis of 1,801 surgically treated clear cell cases, features significantly associated with death were determined and regression coefficients were used to generate a scoring algorithm. Low SSIGN scores correlated with improved survival.

A similar algorithm called the progression score is being used to identify clear cell RCC patients at high risk for progression who make good candidates for clinical trials of adjuvant therapy. Based on retrospective data of 1,671 clear cell patients who underwent surgery at Mayo Clinic between 1970 and 2000 for localized disease, metastasis-free survival has been shown to correlate with a low progression score. A phase III trial of sorafenib, an oral multitargeted kinase inhibitor, is enrolling patients with high or intermediate metastasis risk based on this algorithm.

 

Molecular markers

Molecular prognostic markers have the potential to greatly refine our ability to predict prognosis for RCC patients and may help identify therapeutic targets. As our identification strategies mature, molecules thought to play roles in adhesion, angiogenesis, and tumor growth represent the next wave of prognostic information. For example, B7-H1 is a cell surface glycoprotein that involved in T-cell co-stimulation.

 

Aberrant expression of B7-H1 by RCC tumors may allow tumors to proliferate. Recently, Mayo Clinic investigators demonstrated that RCC marker B7-H1 was associated with higher mortality compared with B7-H1-negative tumors and currently are investigating the potential of targeting B7-H1 therapeutically.

 

Bradley C. Leibovich, MD, is associate professor of urology and director of urologic oncology at the Mayo Clinic in Rochester, Minn.