Case study of the month. Complete histologic remission after sunitinib neoadjuvant therapy in T3b renal cell carcinoma.
ABSTRACT The authors present the first case report of complete histologic remission after neoadjuvant sunitinib treatment on primary renal tumour and vena cava thrombus. A 78-yr-old woman with an Eastern Cooperative Oncology Group (ECOG) score of 0 presented with a T3b renal tumour. She refused surgical treatment but agreed to percutaneous biopsy and medical treatment. A Fuhrman III renal cell carcinoma was histologically confirmed on percutaneous biopsy, and sunitinib treatment was administered over 6 mo. A significant objective response was observed for tumour size and thrombus. The patient finally accepted surgical treatment. Pathologic examination concluded with a complete response of primary tumour and thrombus.
[show abstract] [hide abstract]
ABSTRACT: Since the introduction of tyrosine kinase inhibitors (TKI), treatment of metastatic renal cell carcinoma (RCC) has undergone dramatic changes. However, the use of TKI therapy in adjunctive settings remains to be defined. We present a single-institution experience of patients who received preoperative TKI before nephrectomy for metastatic or unresectable disease. The records of 9 patients with locally advanced or metastatic RCC treated with TKI therapy before nephrectomy at the University of North Carolina were reviewed. All procedures and radiographic images were performed at 1 institution. The cases were surveyed for the effect of TKI on tumor burden and surgical approach and timing. The patients received systemic therapy with either sorafenib or sunitinib before proceeding to nephrectomy on clinical trials for metastatic disease or as the standard of care. The surgery was well tolerated by all patients, without an apparent effect from TKI therapy on the surgical technique or complications. Responses were observed in the primary tumor, as well as in the metastatic sites. Neoadjuvant TKI therapy can induce responses in the primary tumor and has the potential advantage of cytoreduction when administered before nephrectomy for RCC. This setting also potentially provides an opportunity to evaluate the TKI responsiveness of patients with metastatic disease. However, prospective trials evaluating adjunctive surgical approaches to locally advanced and metastatic RCC are needed to determine the significant benefits of TKI therapy and to define the optimal agent, timing of therapy, and disease stage to derive benefit for preoperative therapy.Urology 09/2008; 72(4):864-8. · 2.43 Impact Factor
Article: Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors.[show abstract] [hide abstract]
ABSTRACT: SU11248 sunitinib malate sutent is a selective inhibitor of certain protein tyrosine kinases including VEGF-R types 1-3 PDGF-R-a and -b, c-kit, and RET. Its antitumor activity may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor types. In several phase I/II/III studies, sutent was found to be effective as second and first line treatment in metastatic renal cell carcinoma (RCC). In fact, with a 37% response rate and an additional 48% stable disease sutent became the drug of choice for first line treatment in RCC. Sutent was also effective as second line treatment in patients with gastrointestinal stromal tumors (GIST) with 8% response rate, 70% stable disease and a 20-month median survival. Prolonged stable disease was also documented in neuroendocrine tumors. In addition, a phase II study in multitreated women with breast cancer, sutent demonstrated a moderate activity with 16% clinical benefit. Finally, in non-small cell lung cancer (NSCLC) in patients' progressing on chemotherapy sutent was able to achieve a 10% response rate, a level of activity similar to those documented by other agents approved for lung cancer. The agent is being tested in other tumors with a modified schedule of dosage.The Journal of Steroid Biochemistry and Molecular Biology 03/2008; 108(3-5):261-6. · 3.05 Impact Factor
Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. 2007. N Engl J Med 356 115-24..
Case Study of the Month
Complete Histologic Remission after Sunitinib Neoadjuvant
Therapy in T3b Renal Cell Carcinoma
Gre ´goire Roberta,e,*, Gre ´goire Gabbaya, Raphae ¨l Brama,e, Herve ´ Walleranda,e,
Colette Deminie `reb,e, Franc ¸ois Cornelisc, Jean-Christophe Bernharda,
Alain Ravaudd,e, Philippe Ballangera,e
aBordeaux University Hospital, Department of Urology, Bordeaux, France
bBordeaux University Hospital, Department of Pathology, Bordeaux, France
cBordeaux University Hospital, Department of Radiology, Bordeaux, France
dBordeaux University Hospital, Department of Medical Oncology, Bordeaux, France
eUniversity Bordeaux 2, Victor Segalen, Bordeaux, France
Sunitinib treatment has shown significant improve-
ment in overall survival for metastatic renal cell
carcinoma (RCC)  as well as in significant
metastasis and primary tumour shrinkage . Some
recent publications mentioned promising results
with neoadjuvant therapy [3,4], inducing partial
remission in primary tumour, vena cava thrombus,
and lymph node metastases. In this paper, we
report the first case of complete histologic remis-
sion after sunitinib as neoadjuvant therapy in a T3b
A 78-yr-old woman with an Eastern Cooperative
Oncology Group (ECOG) score of 0 and a history of
hypertension and epilepsy was investigated in our
european urology 55 (2009) 1477–1480
available at www.sciencedirect.com
journal homepage: www.europeanurology.com
Accepted December 25, 2008
Published online ahead of
print on January 9, 2009
Tyrosine kinase inhibitors
The authors present the first case report of complete histologic remis-
sion after neoadjuvant sunitinib treatment on primary renal tumour and
vena cava thrombus. A 78-yr-old woman with an Eastern Cooperative
Oncology Group (ECOG) score of 0 presented with a T3b renal tumour.
She refused surgical treatment but agreed to percutaneous biopsy and
confirmed on percutaneous biopsy, and sunitinib treatment was admi-
nistered over 6 mo. A significant objective response was observed for
tumour size and thrombus. The patient finally accepted surgical treat-
ment. Pathologic examination concluded with a complete response of
primary tumour and thrombus.
# 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Correspondingauthor. Bordeaux University Hospital, Department of Urology, Place Ame ´lie
Raba Le ´on, 33076 Bordeaux Cedex, France. Tel. +33556795547; Fax: +33556795686.
E-mail address: firstname.lastname@example.org (G. Robert).
0302-2838/$ – see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.doi:10.1016/j.eururo.2008.12.036
department in November 2007 for right-flank pain.
Computer tomography (CT) scan and magnetic
resonance imaging (MRI) of the abdomen found a
68-mm tumour on the lower pole of the right kidney.
Early enhancement of the tumour and extension to
the vena cava until the hepatic veins were shown on
MRI after injection (Fig. 1). Thoracic CT scan and
bone-scan excludedmetastaticdisease.According to
the European Association of Urology (EAU) guide-
lines, radical nephrectomy and thrombectomy were
proposed. The patient refusedanykind ofsurgical
treatment but agreed to percutaneous biopsy and
medical treatment. Percutaneous biopsy confirmed
Fuhrman III RCC (Fig. 2). Starting in December 2007,
Fig. 1 – Magnetic resonance image of the abdomen at diagnosis: (a) 68-mm tumour of the right kidney and (b) vena cava
thrombus extension to the hepatic veins.
Fig. 2 – Microscopic examination of the right kidney tumour percutaneous biopsy: Fuhrman III renal cell carcinoma.
Fig. 3 – Magnetic resonance image of the abdomen after four cycles of sunitinib treatment: (a) 35% regression of the renal
tumour and (b) stabilization of the vena cava thrombus.
european urology 55 (2009) 1477–1480
were observed on MRI. Two additive cycles of
sunitinib were administered to the patient at a lower
dose (37.5 mg daily) due to thrombopoenia. Another
MRI was performed in July 2008 and showed
persistence of partial response in the renal tumour
and partial regression of the vena cava thrombus
thickness (Fig. 3).
Because of partial imaging response, surgical
treatment was finally accepted by the patient. A
fifth cycle of sunitinib (37.5 mg daily) was conducted
to plan surgery but was interrupted 6 wk before
surgery. In October 2008, radical nephrectomy and
thrombectomy were performed through an abdom-
inal approach with prior renal artery embolisation.
adherent vena cava thrombus. No complications
were observed during the postoperative period.
Macroscopic examination of the kidney found a
lower-pole tumour with evidence of major necrosis
(Fig. 4). Pathologic examination confirmed com-
plete tumour necrosis without any sign of malig-
nant cells in the kidney or in the thrombus (Fig. 5).
Immunohistochemistry with vimentin, CD10, and
AE1/AE3 antibodies was also negative, confirming
complete tumour necrosis (Fig. 6). With a 3-mo
This case illustrates the potential of neoadjuvant
antiangiogenic therapy in the surgical management
Sunitinib treatment has been widely studied in
metastatic RCC as a complement to radical nephrec-
tomy. It has achieved progression-free and overall
survival improvement more than other treatments
Fig. 6 – Immunohistochemistry with (a) vimentin, (b) CD10, and (c) AE1/AE3 confirm complete necrosis of the tumour.
Fig. 4 – Macroscopic examination of the right kidney: lower-
pole tumour with major evidence of tumour necrosis.
Fig. 5 – Microscopic examination of (a) the tumour and (b) the thrombus: necrosis without any sign of residual malignancy.
european urology 55 (2009) 1477–1480
standard for first-line treatment in metastatic RCC
well as for primary tumour size reduction.
We are reporting the first case of complete
histologic remission after neoadjuvant sunitinib
treatment. The patient had locally advanced RCC
with important extension to the vena cava, and
surgical treatment was difficult. Neoadjuvant ther-
apy reduced surgical risks to make treatment
acceptable to the patient.
effects of sunitinib as neoadjuvant therapy. Shuch
et al  have shown a significant response after
neoadjuvant sunitinib treatment for three patients.
These patients were contraindicated for surgical
treatment because of large tumour size on a solitary
kidney, atrial thrombus, or major lymph node
metastasis. All were accessible to surgical treat-
ment after neoadjuvant treatment, thanks to the
reduction of primary tumour, vena cava thrombus,
and lymph node metastasis. Amin et al  con-
firmed these effects of neoadjuvant sunitinib and
sorafenib on nine patients with locally advanced or
metastatic RCC. Tumour reductions were observed
on the primary tumour a well as in the metastatic
sites. Neoadjuvant treatment permitted radical
nephrectomy. Karakiewicz et al  described
one case of T3b sunitinib neoadjuvant therapy. In
this patient, renal tumour decreased from 11 cm to
8 cm and thrombus downstaged from atria to the
From these observations, we assume that anti-
angiogenic treatments could change strategies of
care for locally advanced or metastatic RCC. It could
allow surgical treatment in some contraindicated
patients or reduce surgical risks. The role of
should be further studied in randomised trials.
Conflicts of interest: A. Ravaud is a member of the global,
European, and/or French boards of Pfizer, Bayer, Schering,
Novartis, Roche, GSK and Wyeth for urologic tumours, and
he receives institutional support for research from Roche, GSK,
and Novartis. G. Robert, G. Gabbay, R. Bram, H. Wallerand,
C. Deminie `re, F. Cornellis, JC. Bernhard, and P. Ballanger have
nothing to disclose.
 Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus
interferon alfa in metastatic renal-cellcarcinoma. N EnglJ
 AminC,Wallen E,PruthiRS, Calvo BF,GodleyPA, Rathmell
WK. Preoperative tyrosine kinase inhibition as an adjunct
to debulking nephrectomy. Urology 2008;72:864–8.
 Shuch B, Riggs SB, LaRochelle JC, et al. Neoadjuvant tar-
geted therapy and advanced kidney cancer: observations
and implications for a new treatment paradigm. BJU Int
 Karakiewicz PI, Suardi N, Jeldres C, et al. Neoadjuvant
sutentinduction therapy mayeffectivelydown-stage renal
cell carcinoma atrial thrombi. Eur Urol 2008;53:845–8.
 Ljungberg B, Hanbury DC, Kuczyk MA, et al. Renal cell
carcinoma guideline. Eur Urol 2007;51:1502–10.
 Motzer RJ, Michaelson MD, Redman BG, et al. Activity of
SU11248, a multitargeted inhibitor of vascular endothelial
growth factor receptor and platelet-derived growth factor
receptor, in patientswith metastatic renal cellcarcinoma.
J Clin Oncol 2006;24:16–24.
 Ravaud A, Wallerand H, Culine S, et al. Update on the
medical treatment of metastatic renal cell carcinoma. Eur
Please visit www.eu-acme.org/europeanurology
to answer the following EU-ACME question online
(the EU-ACME credits will be attributed automa-
Urology guidelines, what is the correct indication
for sunitinib treatment in renal cell carcinoma
to theEuropeanAssociation of
A. Neoadjuvant therapy in locally advanced RCC.
B. Neoadjuvant therapy in metastatic RCC.
C. First-line treatment before radical nephrec-
tomy in metastatic RCC.
D. First-line treatment after radical nephrectomy
in metastatic RCC.
european urology 55 (2009) 1477–1480