EURURO Vol. 73 No. 1

69 148

Platinum Priority – Editorial
Referring to the article published on pp. 62–68 of this issue
Are We Ready for Adjuvant Sunitinib in High-risk Renal Cell
Carcinoma?
Jozefina Casuscelli
a Department of Urology, Ludwig-Maximilians University, Munich, Germany; bMolecular Oncology, Department of Medicine, Siteman Cancer Center,
Washington University, St. Louis, MO, USA
Renal cell carcinoma (RCC), which is predominantly of clear
cell renal histology (ccRCC), is among the most lethal of
urologic malignancies. Despite advances in diagnostic and
surgical techniques, the prognosis for high-risk localized
RCC has seen little improvement in the last decades, and
disease recurrence may occur in as many as 35–40% of
patients harboring high-risk features
Once relapse leads to a metastatic stage after tumor
surgery several novel targeted treatment options can be
offered. However, although the prognosis for metastatic
disease has improved in the past decade, no curative
therapy is currently available. There is therefore an urgent
need to develop strategies to reduce metastatic recurrence
by targeting unrecognized micrometastatic residual disease
in patients with high-risk RCC.
Compared to other malignancies, for which adjuvant
therapy has been extensively studied, limited data are
available on the efficacy of adjuvant treatment in prevent-
ing RCC relapse. The only management currently available
for patients with high risk is close follow-up.
A natural consideration for the design of adjuvant trials in
RCC is to[6_TD$DIFF] employ the VEGF pathway inhibitors sunitinib,
sorafenib, and pazopanib following tumor resection. These
first-generation antiangiogenic compounds have revolution-
ized the treatment of metastatic ccRCC in the past decade,
and were therefore chosen in three adjuvant trials shortly
after their approval in 2006 and 2010. In all studies, patients
were treated for 1 yr with either a VEGF inhibitor or placebo.
The first double-blind, placebo-controlled, randomized,
phase 3 trial (ASSURE, NCT00326898) assigned 1943 patients
1:1:1 to sunitinib, sorafenib, or placebo following resection
of locally advanced RCC The results showed no difference
in the primary endpoints of progression-free survival (PFS)
and overall survival (OS) in the overall population, even after
risk stratification with a focus on high-risk ccRCC
The recently presented preliminary results from the
PROTECT trial (NCT01235962) evaluating the efficacy and
safety of adjuvant pazopanib versus placebo in 1538 patients
did not meet the primary endpoint of disease-free survival
(DFS) for 600 mg pazopanib .
Surprisingly, the second prospective study of this type
(S-TRAC, NCT00375674) with adjuvant sunitinib versus
placebo in high-risk ccRCC met its primary endpoint of
improving DFS (6.8 vs 5.6 yr) . However, the authors were
not able to provide results on the secondary endpoint of OS.
One potential explanation for the differences in ASSURE
and S-TRAC regarding the benefit of sunitinib is the patient
stratification strategy, namely the relatively higher risk
population enrolled in the S-TRAC trial. These patients are
more likely to harbor micrometastases and therefore
potentially benefit from adjuvant therapy.
In this issue of European Urology, Motzer and colleagues
present exploratory subgroup analyses for the S-TRAC
study to precisely define which patients could benefit most
from adjuvant sunitinib, and updated OS data after an
additional 10 mo of follow-up. They showed that the
previously reported positive effect of sunitinib on DFS
persisted in the majority of subgroups, but in particular in
those with high-risk baseline characteristics, defined as T3
stage, no or undetermined nodal involvement, Fuhrman
ava ilable at
journal homepage:
DOI of original article: .
* Corresponding author. Department of Urology, Ludwig-Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany. Tel. +49 4400 0;
Fax: +49 4400 78890.
E-mail address: (J. Casuscelli).
0302-2838/© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.