Impact of pathological tumour characteristics in patients with sarcomatoid renal cell carcinoma

OBJECTIVE Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy. We set out to examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design. PATIENTS AND METHODS A single-centre database was reviewed to identify all patients with sRCC. Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome. RESULTS Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5–30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation. The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis. A total of 85 patients (81.7%) died during the follow-up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7–8.9). In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome. A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool. CONCLUSIONS Both patients with localized and metastatic sRCC have very poor survival outcomes. Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis. A prognostic model, if validated, could aid in patient counselling and/or clinical trial design. Keywords: sarcomatoid, kidney cancer, adjuvant, prognosis, RCC INTRODUCTION Every year ≈ 13,000 men and women die from kidney cancer in the United States [1]. Extensive research has advanced the understanding of RCC from the classic term ‘hypernephroma’ to half a dozen distinct subtypes that have had the mechanisms of malignant transformation characterized. One entity, sarcomatoid RCC (sRCC), is poorly understood and updated classification schemes no longer consider it a distinct subtype [2,3]. These tumours generally coexist with a variable amount of carcinoma (any subtypes) and are generally believed to represent a common pathway of de-differentiation of renal tumours [4]. While only 5% of patients with RCC have sarcomatoid features, these tumours account for 15–20% of patients with advanced disease [5,6]. Improved understanding of the biology of RCC has led to the introduction of six new systemic therapies since 2005. However, agents such as sunitinib, sorafenib and temsirolimus appear to have only limited efficacy in treating patients with sRCC [7–9]. Recently, several clinical trials have specifically targeted patients with sRCC, some of which have stratified patients based on histological features, including clear-cell vs non-clear-cell histology, and by the percentage of sarcomatoid features (PSF) in the primary tumour. Stratification in such trials could help to assess therapeutic response if the histology and the PSF influences the disease biology [10]. However, currently the role of these pathological characteristics in determining biology and outcome is unclear. Clinicians recognize that sarcomatoid tumours are associated with poor outcome, but there are a subset of patients who have exhibited extended survival. Only a limited number of studies have attempted to correlate pathological features with prognosis [5,11]. To better counsel patients with sRCC and to risk-stratify those involved in future clinical trials, we set out to determine the importance of pathological characteristics in patients in a large single-centre cohort of consecutive patients diagnosed with sRCC.