nej mcp 0910041
DESCRIPTION
JURNAL RADIOLOGITRANSCRIPT
clinical practice
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors’ clinical recommendations.
n engl j med 362;7 nejm.org february 18, 2010624
Small Renal MassInderbir S. Gill, M.D., Monish Aron, M.D., Debra A. Gervais, M.D.,
and Michael A.S. Jewett, M.D.
From the Center for Robotic Surgery and Advanced Laparoscopy, USC Institute of Urology, Keck School of Medicine, Univer-sity of Southern California, Los Angeles, (I.S.G., M.A.); the Department of Radiol-ogy, Massachusetts General Hospital, Boston (D.A.G.); and the Division of Urol-ogy, Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto, Toronto (M.A.S.J.). Address re-print requests to Dr. Gill at USC Institute of Urology, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave., Suite 7416, Los Angeles, CA 90089, or at [email protected].
N Engl J Med 2010;362:624-34.Copyright © 2010 Massachusetts Medical Society.
A 65-year-old man with a history of well-controlled hypertension presents for a follow-up visit after an incidental finding of a small mass in the right kidney on an abdominal computed tomographic (CT) scan. (The scan had been ordered to evaluate pain in the lower quadrant, which resolved.) The mass is 3.2 cm in its largest dimension, anterior, heterogeneous, and solid, and it is in the right renal hilum near the main renal artery, vein, and ureter; the left kidney appears normal. The patient feels well, and his physical examination is unremarkable. His serum creatinine level is 1.2 mg per deci-liter (106 μmol per liter). How should this patient be further evaluated and treated?
The Clinic a l Problem
One result of the widespread use of advanced cross-sectional imaging is that small, incidental renal masses have become common radiologic findings. Approximately 13 to 27% of abdominal imaging studies incidentally identify a renal lesion.1,2 The majority of these lesions are small, simple cysts that do not show enhancement after the administration of contrast material, are benign, and require no treatment. A minority of small renal masses are solid masses or complex cystic masses, show contrast enhancement on CT images, and are suggestive of cancer. An enhancing mass is a mass that is seen on CT to have an increase in density of more than 15 Hounsfield units after the administration of contrast material.3
For the purposes of this article, a small renal mass is defined as a contrast-enhancing mass with a largest dimension of 4 cm or less on abdominal imaging.4 From 1988 to 2003, the incidence of small renal masses increased relative to other renal tumors, and they now make up 48 to 66% of all renal tumors that are diagnosed and 38% of all renal tumors that are excised5,6; often the patient has had no symptoms. Of small renal masses, approximately 80% are malignant and 20% are benign.7 When a small renal mass is identified incidentally on imaging, the clinical-management challenge involves distinguishing benign masses from those likely to be malignant and determining the appropriate treatment of malig-nant masses.
S tr ategies a nd E v idence
Radiologic Assessment and Characterization of Renal Masses
Simple renal cysts can be reliably diagnosed noninvasively on the basis of well-defined radiologic criteria. However, the term “cystic mass” is ambiguous, since it spans the spectrum from “definitively benign” to “almost certainly malignant.” The Bosniak classification system8 can be used to assign cystic masses to one of four categories that represent the range of diagnostic possibilities (Fig. 1). Macro-
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Figure 1. Benign Renal Masses.
Unenhanced (Panel A) and enhanced (Panel B) CT scans show no enhancement in a simple cyst (arrows; Bosniak class I) with the density of water and imperceptible walls. An unenhanced CT scan of a minimally complex cyst (Bosniak class IIF) shows discontinuous, slightly thick calcification (Panel C, arrow). An enhanced CT scan of the same cyst shows min-imally thickened internal septation (Panel D, arrow), with perceptible enhancement but no enhancing mural nodules. The Bosniak classification8 categorizes cystic masses on the basis of their radiologic characteristics. Class I lesions are be-nign, nonenhancing simple cysts with thin walls and without any septa, calcifications, or solid components. Class II le-sions are benign cysts with a few hairline-thin septa; perceived enhancement, fine calcification, or a short segment of slightly thickened calcification may be present. Uniformly high-attenuation, well-marginated, nonenhancing lesions 3 cm in diameter or less (so-called high-density cysts) are included in this group. Cysts in this category do not require further evaluation. Class IIF cysts have multiple hairline-thin septa or minimal smooth thickening of the walls or septa that may contain thick and nodular calcification; these cysts do not have measurable contrast enhancement. Totally intrarenal, nonenhancing, high-attenuation renal lesions 3 cm in diameter or less are also included in this category. These lesions require follow-up studies to prove benignity. Class III lesions are indeterminate cysts with thickened irregular or smooth walls or septa in which measurable enhancement is present; some are malignant. Class IV lesions are malignant; they have all the characteristics of class III cysts and also contain enhancing soft-tissue components adjacent to but inde-pendent of the wall or septum. Surgical removal is recommended. A small renal mass is shown in an unenhanced CT scan (Panel E, arrow) and in an enhanced scan (Panel F, arrow), with fat density diagnostic of angiomyolipoma.
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scopic fat within a renal mass, identified by means of CT or magnetic resonance imaging (MRI), is diagnostic of angiomyolipoma (a be-nign mass), unless calcification is present, which would indicate a malignant condition.9
In the case of a solid mass or a complex cystic renal mass, but not a simple cyst, assessment of the size, shape, contour, and tissue-enhancement characteristics is important for determining the likelihood of cancer. Assessment is best per-formed by means of dedicated renal CT scans (with and without the administration of contrast material) or dedicated MRI scans (with and without gadolinium enhancement), obtained at a slice thickness of 3 to 5 mm.
Masses with measurable enhancement on CT or MRI (with the exception of angiomyolipoma) are classified as solid masses or complex cystic masses (Bosniak class III or class IV)8,9 (Fig. 2). The majority of enhancing masses are malignant; no specific findings on imaging conclusively iden-tify a mass as malignant or benign. Thus, when management decisions are being made in the case of a patient with a long life expectancy, a solid, enhancing small renal mass must be considered malignant unless proven otherwise.
The smaller the mass, the greater the chance that it is benign. In a report on 2770 surgically excised solid renal masses stratified according to size, 46% of masses that were less than 1 cm in diameter were benign, as were 22% of those that were 1 to 2.9 cm, and 20% of those that were 3 to 3.9 cm.7 Among masses that are malig-nant, greater size correlates with a higher patho-logical grade. The growth rate of small renal masses is typically slow (2 to 4 mm per year)10; in studies involving relatively short-term follow-up (≤3 years), the growth rate has been reported to be similar for masses subsequently found to be malignant (renal-cell carcinoma) and those found to be benign (oncocytoma).10,11 In one meta-analysis, 30% of small renal masses showed no growth over an observation period of 23 to 39 months.10 Masses that showed no growth were about as likely to be malignant (83%) as were those that grew (89%).12 There are no definable clinical or radiologic characteristics that effec-tively predict future growth; neither size at pre-sentation nor the final histologic diagnosis (even if it is proven renal-cell carcinoma) correlates with growth rates.10 Most excised small renal cancers are classified as low grade. However, in
three studies involving excised renal cancers that were 3 to 4 cm in diameter, 14 to 26% were high grade (grade 3 or 4) and 12 to 36% locally invaded perirenal fat (classified as pT3a tumors).13-15 Patients with small renal masses that lead to symptoms such as flank discomfort or hematu-ria seem to have a worse prognosis than patients with similar-size masses that are detected inci-dentally.16
At the time of diagnosis, metastases are pres-ent in 1 to 8% of patients with renal cancers that are 3 to 4 cm in diameter.10,13-15 An analysis of the National Cancer Institute’s Surveillance, Epi-demiology, and End Results Program database for 1998 to 2003 showed a 5.2% prevalence of metastasis at presentation among 8792 patients
Figure 2 (facing page). Small Renal Masses.
Various radiologic characteristics of small renal masses (e.g., tumor size, location, depth of infiltration, relation-ship to the renal hilum, and status of contralateral kid-ney) affect management decision-making. A right hilar, midrenal, enhancing, small renal mass (Panel A, arrow) is the tumor of the patient presented in the vignette. Hilar tumors are in direct contact with the main renal artery, vein, or both on preoperative CT or MRI. Since they are so close to major renal blood vessels, hilar tu-mors present a special technical challenge during par-tial nephrectomy surgery. In this patient, laparoscopic partial nephrectomy was performed successfully. Panel B shows a cystic left renal mass (arrow) with an en-hancing solid component (Bosniak class IV [a clearly malignant cyst that has thickened irregular or smooth walls or septa in which measurable enhancement is present and that has enhancing soft-tissue components adjacent to, but independent of, the wall or septum; surgical removal is required]). Partial nephrectomy con-firmed cystic renal-cell carcinoma. (Image provided by Peter L. Choyke, M.D.). Panel C shows a completely intra-parenchymal, solid, enhancing, central right renal mass (arrow), 5.5 cm in diameter, in a functionally solitary kidney in an otherwise healthy 72-year-old patient with stage III chronic kidney disease. The atrophic left kidney had extremely poor function and an incidental renal cyst. Laparoscopic partial nephrectomy was performed successfully. Panel D shows an enhancing small renal mass (arrow), 0.9 cm in diameter, in the left kidney. Given the option of active surveillance, the young pa-tient elected laparoscopic partial nephrectomy. Despite the small tumor size, final histologic analysis revealed grade 3 clear-cell renal-cell carcinoma with capsular in-vasion. Panel E shows a left anterior enhancing small renal mass (arrow), 4 cm in diameter. After partial ne-phrectomy, histologic analysis showed an oncocytoma, a benign tumor. (Image provided by Michael Marberger, M.D.) Panel F shows bilateral enhancing small renal masses (arrows). These were treated with bilateral lap-aroscopic partial nephrectomy.
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with pathologically confirmed small renal can-cers (≤4 cm in diameter)17; for each 1-cm increase in the size of the primary cancer, the calculated prevalence of metastases increased by 3.5%.
Needle Biopsy
Typically performed under CT guidance, needle biopsies appear to be safe (with a minimal risk of bleeding or of seeding of the needle tract with malignant cells), and they have a sensitivity for the detection of cancer of 80 to 92% and a speci-ficity of 83 to 100%.18-20 Smaller masses (≤3 cm) have higher false negative rates (negative predic-
tive value, 60%); the false negative rate can be reduced by repeat biopsies and a high level of experience on the part of operators and pathol-ogists.20
In most cases, benign findings on examina-tion of a biopsy specimen cannot rule out cancer in the rest of the tumor, but a definitive benign diagnosis may be made in cases of angiomyoli-poma, metanephric adenoma, or focal infection. A benign diagnosis may be strongly suggested for some oncocytomas, although chromophobe renal-cell carcinoma may have a similar appear-ance on biopsy.19 In the absence of findings that
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are diagnostic of renal-cell carcinoma or a defi-nite benign entity, a biopsy specimen showing nondiagnostic or nonmalignant findings must be considered with caution, and surveillance imaging, repeat biopsy, or surgery should be performed.
Combining histologic and molecular or cyto-genetic techniques may improve the accuracy of a diagnosis that was based on needle biopsy. As compared with histologic analysis alone, the ad-dition of molecular diagnostic algorithms that incorporate RNA extraction and polymerase chain reaction for four gene products to distinguish subtypes of renal-cell carcinoma improved the sensitivity (100% vs. 87%) and negative predic-tive value (100% vs. 87.5%) of needle biopsies for the diagnosis of clear-cell renal-cell carcinoma.21 However, these findings require validation at other centers, and currently, molecular diagnostic algorithms are not used routinely in practice.
management Options
Options for the management of small renal mass-es that are worrisome because of the risk of malig-nant conditions include active surveillance, surgery, and ablation. Data from randomized, controlled trials comparing various treatment options are lacking; thus, available data are observational or are based on case series (Table 1). Decision mak-ing should take into account a patient’s coexist-ing conditions, life expectancy, and preferences and the treatment provider’s level of experience.
Active SurveillanceActive surveillance involves the monitoring of tu-mor size by means of serial ultrasonography, CT, or MRI.22 Although comparative data are lack-ing, CT or MRI is generally preferred over ultra-sonography, owing to greater resolution and re-producibility. The typical recommendation is to perform repeat imaging at intervals of 6 to 12 months; however, the financial costs of serial imaging and the risks associated with radiation from serial CT scanning in particular (30 to 90 mSv per CT study23) should be taken into consider-ation.
The growth of or the metastasis from initial-ly asymptomatic, incidental small renal masses has been extremely uncommon, although the available studies of case series involved a short follow-up, of only 23 to 39 months10; therefore, active surveillance is an attractive option most-
ly for elderly or infirm patients with a short life expectancy. This strategy also seems reasonable for masses that are 1 cm in diameter or smaller, regardless of the patient’s age, although data are needed to help determine the frequency and duration of follow-up imaging in these cases. In selected patients who are undergoing active sur-veillance, intervention can be performed if the tumor grows; such delayed intervention does not seem to compromise future treatment options.24 However, given the limitations of the available data (including relatively short follow-up, limited sample size, and insufficient histologic assess-ment) and the fact that imaging studies can neither definitively rule out cancer nor predict its behavior, active surveillance is not generally rec-ommended for young, healthy patients. However, surveillance data do provide reassurance that treatment is generally not warranted urgently.
Nephron-Sparing SurgeryRadical (total) nephrectomy was for many years the accepted standard treatment for all organ-confined kidney tumors, but nephron-sparing surgery (partial nephrectomy) has now become the preferred treatment for small renal masses for which surgery is warranted. Nephron-sparing surgery, which may be performed by an open or a laparoscopic approach, involves targeted exci-sion of the tumor along with an adequate rim of normal renal parenchyma, thereby preserving the uninvolved portion of that kidney.25 Chronic kid-ney disease is increasingly common (one study showed previously unrecognized chronic kidney disease in one quarter of the patients who had a small renal mass26); therefore, renal functional preservation is an important consideration in man-agement.
In the only randomized trial comparing par-tial with radical nephrectomy for tumors less than 5 cm in diameter, the authors concluded that partial nephrectomy could be safely per-formed but would have slightly higher rates of complications than would radical nephrectomy. The complications included severe hemorrhage (3.1% vs. 1.2%), urine leak (4.4% vs. 0%), and reoperation (4.4% vs. 2.4%). However, this report did not include oncologic outcomes.27 Data from case series have indicated low 5-year and 10-year cancer-specific mortality rates after open partial nephrectomy (2.4% and 5.5%, respectively); these data are similar to the outcomes for radical ne-
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Tabl
e 1.
Tre
atm
ent C
onsi
dera
tions
for
a Pa
tient
with
a S
mal
l Ren
al M
ass.
Trea
tmen
tIn
dica
tions
Con
trai
ndic
atio
nsC
omm
ent
Nee
dle
biop
syKn
own
extr
aren
al o
r sys
tem
ic c
ance
r; lo
bar c
onto
ur d
efor
mity
su
gges
tive
of a
sm
all r
enal
mas
s; c
oexi
stin
g co
nditi
ons
that
con
fer
a po
or s
urgi
cal r
isk;
an
unre
sect
able
mas
s;
som
e hy
pera
tten
uatin
g m
asse
s w
ith h
omog
eneo
us e
n-ha
ncem
ent o
r so
me
inde
term
inat
e cy
stic
lesi
ons
(phy
si-
cian
’s d
iscr
etio
n); s
uspe
cted
foca
l inf
ectio
n; c
hoic
e of
yo
ung
patie
nt; c
onsi
dera
tion
of p
ercu
tane
ous
abla
tion
or
neoa
djuv
ant t
arge
ted
ther
apy
Unc
orre
cted
coa
gulo
path
yN
eedl
e-bi
opsy
spe
cim
en m
ay b
e fa
lsel
y ne
gativ
e, a
nd
som
e sm
all r
enal
mas
ses
may
req
uire
ong
oing
im
agin
g in
the
abse
nce
of a
def
initi
ve d
iagn
osis
.
Act
ive
surv
eilla
nce
Elde
rly,
frai
l pat
ient
; im
port
ant c
oexi
stin
g co
nditi
ons;
poo
r su
rgic
al r
isk;
lim
ited
life
expe
ctan
cy; s
ever
ely
com
pro-
mis
ed r
enal
func
tion;
pat
ient
cho
ice
of n
o in
terv
entio
n
Youn
g, h
ealth
y pa
tient
Dis
cuss
con
tem
pora
ry d
ata
so th
e pa
tient
can
par
tici-
pate
in d
ecis
ion
mak
ing;
act
ive
surv
eilla
nce
mig
ht
be m
ore
broa
dly
appl
icab
le, b
ut m
ore
data
are
ne
eded
to d
eter
min
e w
hich
mas
ses
can
be s
afel
y fo
llow
ed w
ithou
t int
erve
ntio
n.
Part
ial n
ephr
ecto
my
Enha
ncin
g, s
olid
or
com
plex
cys
tic s
mal
l ren
al m
ass
in a
m
edic
ally
fit p
atie
nt; h
ilar
mas
s; in
dica
tions
for
neph
ron-
spar
ing
surg
ery*
Unc
orre
cted
coa
gulo
path
y, s
e-ve
re r
enal
dys
func
tion,
sur
-gi
cally
sca
rred
abd
omen
(r
elat
ive
cont
rain
dica
tion)
Part
ial n
ephr
ecto
my
is th
e st
anda
rd n
ephr
on-s
pari
ng
surg
ical
opt
ion
beca
use
it ha
s th
e m
ost d
urab
le
follo
w-u
p da
ta (
up to
15
yr)
conc
erni
ng o
ncol
ogy
and
rena
l fun
ctio
n an
d ca
n be
per
form
ed b
y m
eans
of
a la
paro
scop
ic, o
pen
surg
ical
, or
robo
tic a
p-pr
oach
, dep
endi
ng o
n av
aila
ble
expe
rtis
e.
Imag
e-gu
ided
tum
or a
blat
ion
(cry
oabl
atio
n or
rad
io-
freq
uenc
y ab
latio
n)
A s
mal
l tum
or (
≤3 c
m in
dia
met
er)
in a
n el
derl
y, h
igh-
risk
pa
tient
who
opt
s ag
ains
t act
ive
surv
eilla
nce
and
wan
ts
inte
rven
tion;
sev
ere
rena
l dys
func
tion;
sur
gica
lly s
carr
ed
abdo
men
; a s
mal
l ren
al m
ass
in a
pos
tope
rativ
e re
nal
rem
nant
; the
req
uest
of a
n in
form
ed y
oung
er p
atie
nt
Hea
lthy
patie
nt ≤
70 y
r of
age
(b
ecau
se lo
ng-t
erm
onc
o-lo
gic
data
are
lack
ing)
, tu-
mor
s >4
cm
in d
iam
eter
(ris
k of
inco
mpl
ete
tum
or a
bla-
tion)
, hila
r tu
mor
s (r
isk
of
inju
ry to
rena
l ves
sels
), u
n-co
rrec
ted
coag
ulop
athy
The
mai
n lim
itatio
n to
pro
be a
blat
ion
is th
e la
ck o
f ro
bust
long
-ter
m o
ncol
ogic
dat
a.
Rad
ical
nep
hrec
tom
yC
entr
ally
loca
ted
smal
l ren
al m
ass
enm
eshe
d be
twee
n th
e br
anch
es o
f the
mai
n re
nal v
esse
ls (
if ex
cisi
on o
f the
tu-
mor
wou
ld c
ompr
omis
e th
e m
ajor
ves
sels
and
the
col-
lect
ing-
syst
em c
ontin
uity
of t
he r
enal
rem
nant
); s
peci
fic
requ
est o
f an
info
rmed
pat
ient
Indi
catio
ns a
nd s
uita
bilit
y fo
r ne
phro
n-sp
arin
g su
rger
yFo
r sm
all r
enal
mas
ses,
rad
ical
nep
hrec
tom
y sh
ould
ra
rely
be
perf
orm
ed; n
ephr
on-s
pari
ng s
urge
ry d
e-liv
ers
sim
ilar
onco
logi
c an
d su
peri
or fu
nctio
nal
outc
omes
; if n
ephr
on-s
pari
ng s
urge
ry w
ould
be
too
tech
nica
lly c
ompl
ex, a
rad
ical
nep
hrec
tom
y ca
n be
pe
rfor
med
.
* In
dica
tions
for
neph
ron-
spar
ing
surg
ery
are
abso
lute
(bi
late
ral t
umor
s, a
tum
or in
one
kid
ney,
or
a po
orly
func
tioni
ng o
r no
nfun
ctio
ning
opp
osite
kid
ney)
, rel
ativ
e (r
enal
dys
func
tion;
he
redi
tary
ren
al-c
ell c
arci
nom
a; a
gen
etic
pre
disp
ositi
on t
o m
etac
hron
ous
rena
l-cel
l car
cino
ma;
sys
tem
ic t
hrea
ts t
o fu
ture
ren
al fu
nctio
n, s
uch
as d
iabe
tes,
hyp
erte
nsio
n, o
r ne
phro
toxi
c ch
emot
hera
py; o
r lo
cal t
hrea
ts t
o ei
ther
kid
ney,
suc
h as
obs
truc
tive
urop
athy
, sto
ne d
isea
se, o
r re
nova
scul
ar d
isea
se),
or
elec
tive
(a s
mal
l ren
al m
ass
and
a no
rmal
opp
osite
kid
ney)
.
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phrectomy.25,28 In an observational study com-paring partial with radical nephrectomy, partial nephrectomy was associated with a significantly lower risk of renal insufficiency (12% vs. 22%) and proteinuria (35% vs. 55%) at the 10-year follow-up.29 In one report, the risk of stage 3 or higher chronic kidney disease was 20% after partial nephrectomy and 65% after radical neph-rectomy (P<0.001).26 The observation that meta-
chronous tumors occur in the contralateral kidney in 4 to 10% of patients further underscores the value of nephron preservation.6 In contemporary practice, radical nephrectomy is limited to the infrequent instances in which it is warranted for anatomical or technical reasons (Table 1).
Open partial nephrectomy, the reference nephron-sparing procedure, is typically performed through a 6-in. or larger muscle-cutting incision in the flank, often with removal of a lower rib. Up to 50% of patients may have persistent inci-sional complications, such as flank bulge, discom-fort, paresthesias, or hernia.30,31
Laparoscopic Partial NephrectomyMinimally invasive nephron-sparing procedures include laparoscopic or robotic32 partial nephrec-tomy and image-guided thermal ablation (Fig. 3). In a large, retrospective, multi-institutional study comparing outcomes of laparoscopic partial ne-phrectomy with those of open partial nephrec-tomy for category T1 tumors that were 7 cm in diameter or smaller (78% of which were small renal masses), the treatment groups had similar rates of intraoperative complications (≤1.8%) and of positive surgical margins for cancer (≤1.6%), although the open-partial-nephrectomy group had more coexisting conditions and larger tumors. At the 3-year follow-up, oncologic outcomes and renal functional outcomes were similar.33 How-ever, the laparoscopic-partial-nephrectomy group had a longer ischemia time than the open-partial-
A Laparoscopic partial nephrectomy
B Cryoablation
Tumor removed along with overlying
perirenal fat
Suctionaspirator
Transient, atraumatic
clamping of the renal hilum
Needle driver
Cytocidal temperatures
applied to tumor
An ice ball is created to extend 1 cm beyond the edge of the
tumor circumferentially
Tumor
Tumor
3
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Nephron-sparing therapies
Figure 3. Nephron-Sparing Procedures.
Nephron-sparing surgery (partial nephrectomy) is the preferred treatment for small renal masses for which surgery is warranted. Partial nephrectomy can be per-formed by a laparoscopic (Panel A), an open, or a ro-botic approach.32 The procedure often involves transi-ently occluding the blood supply to the kidney with vascular clamps to create a bloodless field for excision of the tumor along with a rim of normal parenchyma. After tumor excision, transected intrarenal blood ves-sels and the collecting system are repaired with sutures to secure hemostasis and water-tight closure. To mini-mize ischemic renal injury, the clamp time should be less than 20 to 30 minutes. Treatment with thermal ab-lation includes cryoablation (Panel B), which aims to freeze the entire tumor to −20 to −40°C, and radio-frequency ablation, which aims to heat it to 60 to 100°C. Either can be performed percutaneously (with image guidance) or laparoscopically by inserting at least one needle applicator directly into the small renal mass to deliver the specific cytocidal thermal energy. The ther-mally ablated tumor is not excised but remains in situ.
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nephrectomy group (30 minutes vs. 20 minutes) and higher rates of postoperative hemorrhage (4.2% vs. 2%).33 Our recently described “early un-clamping” technique during laparoscopic partial nephrectomy has resulted in lower ischemia times (mean, 14 minutes) and lower postopera-tive hemorrhage rates, approximating those re-ported with open partial nephrectomy.34,35 An observational study comparing laparoscopic and open partial nephrectomy showed similar 7-year overall mortality rates (16.9% and 16.5%, respec-tively) and cancer-specific mortality rates (3.1% and 2.3%, respectively).36
Laparoscopic partial nephrectomy is now used even for technically challenging small renal masses that are hilar, central, completely intra-renal, or located in a solitary kidney.37,38 Obser-vational data indicate that laparoscopic partial nephrectomy is associated with shorter recovery times than is open partial nephrectomy.37 It should be noted that the laparoscopic procedure requires technical expertise, and studies showing good outcomes have been performed at selected tertiary centers.35,38 If laparoscopic expertise is lacking, open partial nephrectomy should be performed.
Thermal AblationThermal ablation is performed by inserting nee-dle applicators within the renal mass to generate cytocidal temperatures.39 Cryoablation and radio-frequency ablation are the most common meth-ods and are typically performed after needle bi-opsy for tissue diagnosis.
Data from a case series of 80 patients who underwent laparoscopic cryoablation, with a me-dian follow-up of 8 years, indicate that cryoab-lated small renal masses gradually autoabsorb and shrink in size by an average of 57% at 1 year, 72% at 3 years, and 89% at 5 years, with 73% of cryoablated masses being undetectable on MRI at 5 years.40 At 10 years, overall mortality and cancer-specific mortality rates were 49% and 17%, respectively (31% of the patients had under-gone previous surgery for metachronous renal-cell carcinoma).41 With refinements in probe size and design, a percutaneous image-guided ap-proach may be preferable to a laparoscopic ap-proach for thermal ablation, since procedure-associated morbidity would be lower.
Initial experiences with percutaneous radio-frequency ablation also indicate favorable short-
term outcomes,42 although long-term data are not available. In three case series involving 286 patients who underwent radiofrequency ablation and were followed for an average of 1.2 to 2.3 years, tumor control was achieved in 90% of the patients.42-44 Tumor control was defined as an ab-sence of contrast enhancement on CT or MRI.45
Complications have been reported in approxi-mately 10% of patients who have undergone cryoablation (hemorrhage in 1%, reoperation in 1%, pulmonary complications related to coexist-ing conditions in approximately 5%, and con-gestive heart failure related to coexisting condi-tions in 1%).41 Complications have been reported in approximately 10% of patients who have un-dergone radiofrequency ablation (hemorrhage in 1 to 5%, ureteral injury or stricture in 2%, and severe neuropathic pain in 1.6%).42,43 After ther-mal ablation, follow-up is empirically recom-mended at intervals of 6 to 12 months with dedicated MRI or CT, although data on appro-priate follow-up intervals are lacking. Evidence of residual enhancement or growth in lesion size would suggest the need for additional therapy, including repeat ablation.
A R E A S OF UNCERTA IN T Y
It is currently not possible to predict which small renal masses are likely to pose problems over the long term if left untreated. Although more of these “preclinical” (and presumably curable) re-nal tumors are being treated now than in the past, rates of death from kidney cancer continue to rise, suggesting that at least some small renal masses represent indolent cancers that may not require intervention.46
Nearly one third of elderly persons die from unrelated coexisting conditions within 5 years after curative surgery for kidney cancer. There-fore, the benefit of intervention in the elderly must be weighed against the risks posed by co-existing conditions.47
The optimal frequency of follow-up imaging for small renal masses that are monitored with-out intervention and the appropriate duration of follow-up in cases that show prolonged stability are uncertain. For guidance in the management of small renal masses, additional research is needed to identify reliable markers of cancer and prognosis. The value of cytogenetic markers in improving the diagnostic accuracy of needle-
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biopsy specimens warrants further assessment. Data from randomized trials comparing outcomes of surveillance, surgical interventions, and abla-tion are lacking to inform treatment recommen-dations for individual patients. Follow-up data on long-term outcomes are needed for thermal ablation, including prospective comparison of cryoablation and radiofrequency ablation; in the meantime, surgery is considered the standard of care. Figure 4 shows a suggested management algorithm for a sporadic small renal mass.
Guidelines
The recommendations proposed in this article are largely concordant with the 2007 guidelines of the European Association of Urology for pa-tients with renal-cell carcinoma and the 2009 guidelines of the American Urological Associa-tion for patients with a small renal mass.48,49 However, owing to the absence of randomized trials, these guidelines are based mostly on ex-pert opinion.
6 col33p9
Single sporadic small renal mass — not definitivelybenign according to imaging studies
Relatively young patients (<70 yr)No major coexisting conditionGood life expectancyGood surgical risk
Elderly patients (≥70 yr)Coexisting conditionLimited life expectancyCompromised renal functionPoor surgical risk
Preferred option: surgery
Partial nephrectomytechnically feasible
Partial nephrectomytechnically difficult
Preferred option if tumor increasesin size, patient desiresactive treatment, or both:
Percutaneous thermal ablationCryoablationRadiofrequency ablation
Laparoscopic or openpartial nephrectomy,
depending on availablesurgical expertise
Image-guided ablation(percutaneous or laparoscopic)
CryoablationRadiofrequency
ablationLaparoscopic radical
nephrectomy if ther-mal ablation not safeor not technicallyfeasible
AUTHOR:
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RETAKE:
SIZE
4-C H/TLine Combo
Revised
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1st2nd
3rd
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Consider needle biopsyConsider active surveillanceConsider thermal ablation
Discuss active surveillanceand thermal ablation
Consider needle biopsy
Figure 4. Suggested Algorithm for Management of a Small Renal Mass.
If the patient is relatively young (<70 years) and healthy, needle biopsy should be considered and the current litera-ture about active surveillance and thermal ablation should be discussed with the patient, even though active surveil-lance is not recommended. Tumor size is an important factor that must be considered when finalizing the treatment plan. For example, a spherical 1-cm tumor has a volume of 0.5 ml, whereas a 4-cm tumor has a volume of 33.5 ml, implying considerably greater tumor burden.
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Conclusions a nd R ecommendations
The patient in the vignette has a solid, enhancing small renal mass (Fig. 2A). The patient should understand the serious concern about cancer but also the small possibility that his tumor may be benign or indolent. A core needle biopsy can be considered. Potential treatment approaches should be discussed. Although available data on natural history suggest that the risk of metastasis or growth to a size that would compromise future treatment options is low during the next couple of years, we would recommend surgery (specifi-cally, partial nephrectomy), given his otherwise
good health. The hilar location of this tumor ar-gues against the use of image-guided ablation, which can cause thermal injury to the adjacent renal vessels, the ureter, or both. If partial neph-rectomy is performed and pathological studies confirm the diagnosis of cancer, available data suggest that this patient’s chances of survival, freedom from local recurrence, and preserved re-nal function at 10 years are greater than 90%.28
Dr. Gill reports having equity options in Hansen Medical; Dr. Gervais, receiving grant support from Covidien; and Dr. Jewett, receiving consulting fees from Pfizer, Novartis, Glaxo Smith Kline, and Viventia Biotech and grant support from Wyeth. No other potential conflict of interest relevant to this article was reported.
We thank Peter L. Choyke, M.D., Program Director, Molecular Imaging Program, National Institutes of Health, for reviewing and critiquing a previous version of the manuscript.
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collections of articles on the journal’s web site
The Journal’s Web site (NEJM.org) sorts published articles into more than 50 distinct clinical collections, which can be used as convenient
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