MVD correlated with Fuhrman grade 1-2 (P < 0.001),
clear cell histology (P < 0.001), and absence of necrosis
(P < 0.001) but not with gender, age, sarcomatoid features,
lymphovascular invasion, or tumor size.
Conclusion: High MVD in resected high-risk RCC patients
is an independent prognostic, rather than predictive,
biomarker of improved OS. Further studies should assess
whether incorporating MVD into clinical models will
enhance our ability to predict outcome and if low MVD
can be used for selection of high-risk patients for adjuvant
therapy trials.
Multicenter Validation of Enhancer of Zeste Homolog 2
Expression as an Independent Prognostic Marker in Localized
Clear Cell Renal Cell Carcinoma. Ho TH, Kapur
P, Eckel-Passow JE, et al. J Clin Oncol. 2017 Nov 10;
35(32):3706-3713. doi: 10.1200/JCO.2017.73.3238.
Summary: Enhancer of zeste homolog 2 (EZH2), a chromatin
remodeler, is implicated in the pathogenesis of clear
cell renal cell carcinoma (ccRCC). However, the effect of
EZH2 on outcomes in localized ccRCC is unclear, and
molecular biomarkers are not currently integrated into
prognostic models or adjuvant therapy trials. Methods We
performed Cox regression to evaluate the association of
tumor-based EZH2 gene and protein expression with
survival in three independent cohorts: a cohort from The
Cancer Genome Atlas (n = 532), a cohort from University
of Texas Southwestern Medical Center (n = 122), and a cohort
from Mayo Clinic (n = 1,338). Analyses were adjusted
for the prognostic stage, size, grade, and necrosis (SSIGN)
score as well as within low-, intermediate-, and high-risk
SSIGN groups. Results Patients in The Cancer Genome
Atlas cohort with EZH2-high gene expression were 1.5
times more likely to experience overall death than patients
with EZH2-low expression (95% CI, 1.1 to 2.3; P = .028).
Patients in the University of Texas Southwestern Medical
Center cohort with EZH2-high protein expression were
two times more likely to experience overall death than
patients with EZH2-low expression (95% CI, 1.1 to 4.4;
P = .034). Similarly, patients in the Mayo Clinic cohort
with EZH2-high protein expression were 1.4 times more
likely to experience overall death (95% CI, 1.2 to 1.7;
P < .001). Patients in the Mayo Clinic cohort with EZH2-
high protein expression were nearly two times more likely
to experience RCC-specific death (95% CI, 1.5 to 2.6;
P < .001); EZH2 protein expression was particularly prognostic
among patients with low-risk SSIGN tumors
(HR, 6.1; 95% CI, 3.4 to 11.1; P < .001).
110 Kidney Cancer Journal
Conclusion: EZH2 expression accurately predicts risk of
RCC death beyond existing clinicopathologic models,
particularly in low- and intermediate-risk SSIGN tumors.
Further studies are required to incorporate molecular
biomarkers into surveillance guidelines and adjuvant
clinical trials.
Adjuvant Sunitinib for High-risk Renal Cell Carcinoma
After Nephrectomy: Subgroup Analyses and
Updated Overall Survival Results. Motzer RJ, Ravaud A,
Patard JJ, et al. Eur Urol. 2017 Sep 26. Pii: S0302-
2838(17)30772-8. Doi: 10.1016/j.eururo.2017.09.008.
Summary: Adjuvant sunitinib significantly improved
disease-free survival (DFS) versus placebo in patients with
locoregional renal cell carcinoma (RCC) at high risk of recurrence
after nephrectomy (hazard ratio HR 0.76, 95%
confidence interval CI 0.59-0.98; P=0.03). To report the
relationship between baseline factors and DFS, pattern of
recurrence, and updated overall survival (OS). Data for 615
patients randomized to sunitinib (n=309) or placebo
(n=306) in the S-TRAC trial. Subgroup DFS analyses by
baseline risk factors were conducted using a Cox proportional
hazards model. Baseline risk factors included: modified
University of California Los Angeles integrated staging
system criteria, age, gender, Eastern Cooperative Oncology
Group performance status (ECOG PS), weight, neutrophilto
lymphocyte ratio (NLR), and Fuhrman grade. Of 615
patients, 97 and 122 in the sunitinib and placebo arms
developed metastatic disease, with the most common sites
of distant recurrence being lung (40 and 49), lymph node
(21 and 26), and liver (11 and 14), respectively. A benefit
of adjuvant sunitinib over placebo was observed across
subgroups, including: higher risk (T3, no or undetermined
nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4
and/or nodal involvement; hazard ratio HR 0.74, 95%
confidence interval CI 0.55-0.99; P=0.04), NLR ≤3 (HR
0.72, 95% CI 0.54-0.95; P=0.02), and Fuhrman grade 3/4
(HR 0.73, 95% CI 0.55-0.98; P=0.04). All subgroup analyses
were exploratory, and no adjustments for multiplicity were
made. Median OS was not reached in either arm (HR 0.92,
95% CI 0.66-1.28; P=0.6); 67 and 74 patients died in
the sunitinib and placebo arms, respectively.
Conclusion: A benefit of adjuvant sunitinib over placebo
was observed across subgroups. The results are consistent
with the primary analysis, which showed a benefit for
adjuvant sunitinib in patients at high risk of recurrent
RCC after nephrectomy. Most subgroups of patients
at high risk of recurrent renal cell carcinoma after
nephrectomy experienced a clinical benefit with
adjuvant sunitinib. KCJ
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