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

Abstract

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.

Impact of Rhabdoid Differentiation on Prognosis for Patients with Grade 4 Renal Cell Carcinoma

“…In our multivariable analysis, there was not a statistically significant association between the presence of rhabdoid differentiation and death from RCC (HR: 0.95; p = 0.75); sarcomatoid differentiation was shown to be a statistically significant prognostic feature after multivariable adjustment (HR: 1.63; p < 0.001), consistent with the results of prior studies on sarcomatoid differentiation [5][6][7][8][9].…”

Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma

“…ccRCC tumors featuring sarcomatoid transformation were reviewed by a genitourinary (GU) pathologist (J.W.S.). The clinical data, tumor characteristics, and survival have been described (1,4,20). A second GU pathologist (M.J.M.)…”

“…Although once believed to represent a distinct subtype of RCC, it is now considered a specific histologic feature (3). Whereas sarcomatoid features are found in all forms of kidney cancer, >65% of cases are found with clear cell RCC (ccRCC) (4,5). When sarcomatoid features are present, renal tumors generally are large (median size 10 cm), invasive (20%), and/or metastatic (50%) at presentation (4,5).…”

“…These tumors, when metastatic, have among the poorest survival of all genitourinary malignancies, with a median survival of only 6 mo (1, 2, 4). Even with resected localized disease, nearly 75% recur and have a median survival of <2 y (4,8). The response to systemic therapy is poor, with rare durable responses occurring with any therapeutic strategy (9-12).…”

“…Whereas sarcomatoid features are found in all forms of kidney cancer, >65% of cases are found with clear cell RCC (ccRCC) (4,5). When sarcomatoid features are present, renal tumors generally are large (median size 10 cm), invasive (20%), and/or metastatic (50%) at presentation (4,5). Whereas all such tumors are considered to be Fuhrman grade IV (6), their prognosis is significantly worse compared with other high-grade tumors (7).…”