Nej Mcp 0910041

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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The New England Journal of Medicine Downloaded from nejm.org on September 29, 2014. For personal use only. No other uses without permission.

Copyright © 2010 Massachusetts Medical Society. All rights reserved.

clinical pr actice

n engl j med 362;7 nejm.org february 18, 2010 625

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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.





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.



clinical pr actice


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-



clinical pr actice


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)

.





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.



clinical pr actice


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-





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:

FIGURE:

RETAKE:

SIZE

4-C H/TLine Combo

Revised



1st2nd

3rd

Gill

4 of 4

ARTIST:

TYPE:

ts

02-18-10JOB: 36217 ISSUE:

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.



clinical pr actice


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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