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.

Full text

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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
1.Case report
Sunitinib treatment has shown significant improve-
ment in overall survival for metastatic renal cell
carcinoma (RCC) [1] as well as in significant
metastasis and primary tumour shrinkage [2]. 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
RCC.
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
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Article info
Article history:
Accepted December 25, 2008
Published online ahead of
print on January 9, 2009
Keywords:
RCC
Renal cancer
Sunitinib
Tyrosine kinase inhibitors
Locally advanced
Thrombus
Neoadjuvant
Abstract
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
medicaltreatment.AFuhrmanIIIrenalcellcarcinoma washistologically
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: gregoire.robert@chu-bordeaux.fr (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

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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[5]. 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,
sunitinibwasadministered50 mgdailyfor4wkevery
6 wk.
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.
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Aftertwocyclesoftreatment,35%regressionofthe
renaltumourandstabilityofthevenacavathrombus
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.
Thenephrectomyrevealedtightperirenaltissuesand
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
follow-up,noevidenceoflocalormetastaticdisease
was found.
2.Discussion
This case illustrates the potential of neoadjuvant
antiangiogenic therapy in the surgical management
of RCC.
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.
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[1,6].Itiscurrentlyconsideredtobethenewreference
standard for first-line treatment in metastatic RCC
[7].Ithasprovenefficacyformetastasisregressionas
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.
Otherrecentpublicationsarereportinginteresting
effects of sunitinib as neoadjuvant therapy. Shuch
et al [3] 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 [2] 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 [4] 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
renal vein.
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
antiangiogenicagentsas
should be further studied in randomised trials.
neoadjuvanttherapy
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.
References
[1] Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus
interferon alfa in metastatic renal-cellcarcinoma. N EnglJ
Med 2007;356:115–24.
[2] AminC,Wallen E,PruthiRS, Calvo BF,GodleyPA, Rathmell
WK. Preoperative tyrosine kinase inhibition as an adjunct
to debulking nephrectomy. Urology 2008;72:864–8.
[3] 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
2008;102:692–6.
[4] Karakiewicz PI, Suardi N, Jeldres C, et al. Neoadjuvant
sutentinduction therapy mayeffectivelydown-stage renal
cell carcinoma atrial thrombi. Eur Urol 2008;53:845–8.
[5] Ljungberg B, Hanbury DC, Kuczyk MA, et al. Renal cell
carcinoma guideline. Eur Urol 2007;51:1502–10.
[6] 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.
[7] Ravaud A, Wallerand H, Culine S, et al. Update on the
medical treatment of metastatic renal cell carcinoma. Eur
Urol 2008;54:315–25.
EU-ACME question
Please visit www.eu-acme.org/europeanurology
to answer the following EU-ACME question online
(the EU-ACME credits will be attributed automa-
tically).
Question:
According
Urology guidelines, what is the correct indication
for sunitinib treatment in renal cell carcinoma
(RCC)?
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.
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