You are on page 1of 11

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

clinical practice

Small Renal Mass


Inderbir S. Gill, M.D., Monish Aron, M.D., Debra A. Gervais, M.D.,
and Michael A.S. Jewett, M.D.
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.
From the Center for Robotic Surgery and
Advanced Laparoscopy, USC Institute of
Urology, Keck School of Medicine, University of Southern California, Los Angeles,
(I.S.G., M.A.); the Department of Radiology, Massachusetts General Hospital,
Boston (D.A.G.); and the Division of Urology, Department of Surgical Oncology,
Princess Margaret Hospital, University of
Toronto, Toronto (M.A.S.J.). Address reprint 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 gillindy@gmail.com.
N Engl J Med 2010;362:624-34.
Copyright 2010 Massachusetts Medical Society.

An audio version
of this article
is available at
NEJM.org

A 65-year-old man with a history of well-controlled hypertension presents for a followup 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 deciliter (106 mol per liter). How should this patient be further evaluated and treated?

The Cl inic a l Probl em


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 contrastenhancing 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 malignant masses.

S t r ategie s a nd E v idence
Radiologic Assessment and Characterization of Renal Masses

Simple renal cysts can be reliably diagnosed noninvasively on the basis of welldefined 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). Macro624

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

clinical pr actice

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)
RETAKE
1st
AUTHOR
shows discontinuous, slightly thick ICM
calcification
(PanelGillC, arrow). An enhanced
CT scan
of the same cyst shows min2nd
REG F FIGURE
1a-f
imally thickened internal septation (Panel
D, arrow), with
perceptible enhancement but 3rd
no enhancing mural nodules. The
CASE
TITLE on the basis of their radiologic
Bosniak classification8 categorizes cystic
masses
characteristics. Class I lesions are beRevised
EMail
Linesepta,4-C
nign, nonenhancing simple cysts with thin walls and without any
calcifications,
or solid components. Class II leSIZE
Enon
ARTIST:
H/T
sions are benign cysts with a few hairline-thin
septa; mst
perceivedH/T
enhancement,
fine calcification, or a short segment of
FILL
33p9
Combo
slightly thickened calcification may be present. Uniformly high-attenuation, well-marginated, nonenhancing lesions 3 cm
AUTHOR,
PLEASE
NOTE:
in diameter or less (so-called high-density cysts) are included in this group. Cysts in this category do not require further
Figure has been redrawn and type has been reset.
evaluation. Class IIF cysts have multiple hairline-thinPlease
septacheck
or minimal
carefully.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 renalJOB:
lesions
3 cm in diameter or less
are also
included in this category. These lesions
36207
2-18-10
ISSUE:
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 independent 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.

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

625

The

n e w e ng l a n d j o u r na l

scopic fat within a renal mass, identified by


means of CT or magnetic resonance imaging
(MRI), is diagnostic of angiomyolipoma (a benign 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 performed 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 identify 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 malignant, greater size correlates with a higher pathological 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 metaanalysis, 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 effectively predict future growth; neither size at presentation 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
626

of

m e dic i n e

Figure 2 (facing page). Small Renal Masses.


Various radiologic characteristics of small renal masses
(e.g., tumor size, location, depth of infiltration, relationship to the renal hilum, and status of contralateral kidney) 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 tumors present a special technical challenge during partial nephrectomy surgery. In this patient, laparoscopic
partial nephrectomy was performed successfully. Panel
B shows a cystic left renal mass (arrow) with an enhancing 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 confirmed cystic renal-cell carcinoma. (Image provided by
Peter L. Choyke, M.D.). Panel C shows a completely intraparenchymal, 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 patient elected laparoscopic partial nephrectomy. Despite
the small tumor size, final histologic analysis revealed
grade 3 clear-cell renal-cell carcinoma with capsular invasion. Panel E shows a left anterior enhancing small
renal mass (arrow), 4 cm in diameter. After partial nephrectomy, 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 laparoscopic partial nephrectomy.

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 hematuria seem to have a worse prognosis than patients
with similar-size masses that are detected incidentally.16
At the time of diagnosis, metastases are present 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 Institutes Surveillance, Epidemiology, and End Results Program database
for 1998 to 2003 showed a 5.2% prevalence of
metastasis at presentation among 8792 patients

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

clinical pr actice

with pathologically confirmed small renal cancers (4 cm in diameter)17; for each 1-cm increase
Gill
ICM
in the size of the primary cancer,
theAUTHOR
calculated
REG F FIGURE
2a-f
prevalence of metastases increased
by
3.5%.
CASE
TITLE

tive value, 60%); the false negative rate can be


reduced by repeat biopsies and a high level of
RETAKE
1st
experience on
the part
of operators and pathol2nd
20
ogists.
3rd
Revised
EMail
LineIn most
4-C cases, benign findings on examinaEnon
Needle Biopsy
ARTIST: mst
tion
biopsySIZE
specimen cannot rule out cancer
H/T of a
H/T
FILL
33p9
Combo
Typically performed under CT guidance, needle in the rest of the
tumor, but a definitive benign
AUTHOR, PLEASE NOTE:
biopsies appear to be safe (with a minimal
risk
of
diagnosis
may
be
Figure has been redrawn and type has been reset. made in cases of angiomyolicarefully.
bleeding or of seeding of the needle tractPlease
withcheck
poma,
metanephric adenoma, or focal infection.
malignant cells), and they have a sensitivity for A benign diagnosis may be strongly suggested
JOB: 36207
ISSUE: 2-18-10
the detection of cancer of 80 to 92% and a speci- for some oncocytomas, although chromophobe
18-20
ficity of 83 to 100%.
Smaller masses (3 cm) renal-cell carcinoma may have a similar appearhave higher false negative rates (negative predic- ance on biopsy.19 In the absence of findings that
n engl j med 362;7 nejm.org february 18, 2010

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

627

The

n e w e ng l a n d j o u r na l

are diagnostic of renal-cell carcinoma or a definite 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 cytogenetic techniques may improve the accuracy of
a diagnosis that was based on needle biopsy. As
compared with histologic analysis alone, the addition 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 predictive 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.

of

m e dic i n e

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 patients 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 surveillance, 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 assessment) and the fact that imaging studies can
neither definitively rule out cancer nor predict its
behavior, active surveillance is not generally recommended for young, healthy patients. However,
surveillance data do provide reassurance that
treatment is generally not warranted urgently.
Nephron-Sparing Surgery

management Options

Options for the management of small renal masses that are worrisome because of the risk of malignant 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 making should take into account a patients coexisting conditions, life expectancy, and preferences
and the treatment providers level of experience.
Active Surveillance

Active surveillance involves the monitoring of tumor size by means of serial ultrasonography, CT,
or MRI.22 Although comparative data are lacking, CT or MRI is generally preferred over ultrasonography, owing to greater resolution and reproducibility. 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 consideration.
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 most628

Radical (total) nephrectomy was for many years


the accepted standard treatment for all organconfined 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 excision of the tumor along with an adequate rim of
normal renal parenchyma, thereby preserving the
uninvolved portion of that kidney.25 Chronic kidney 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 management.
In the only randomized trial comparing partial with radical nephrectomy for tumors less
than 5 cm in diameter, the authors concluded
that partial nephrectomy could be safely performed 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-

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

Enhancing, solid or complex cystic small renal mass in a


medically fit patient; hilar mass; indications for nephronsparing surgery*

A small tumor (3 cm in diameter) in an elderly, high-risk


patient who opts against active surveillance and wants
intervention; severe renal dysfunction; surgically scarred
abdomen; a small renal mass in a postoperative renal
remnant; the request of an informed younger patient

Centrally located small renal mass enmeshed between the


branches of the main renal vessels (if excision of the tumor would compromise the major vessels and the collecting-system continuity of the renal remnant); specific
request of an informed patient

Partial nephrectomy

Image-guided tumor ablation


(cryoablation or radio
frequency ablation)

Radical nephrectomy

Contraindications

Comment

Partial nephrectomy is the standard nephron-sparing


surgical option because it has the most durable
follow-up data (up to 15 yr) concerning oncology
and renal function and can be performed by means
of a laparoscopic, open surgical, or robotic approach, depending on available expertise.

Discuss contemporary data so the patient can participate in decision making; active surveillance might
be more broadly applicable, but more data are
needed to determine which masses can be safely
followed without intervention.

Needle-biopsy specimen may be falsely negative, and


some small renal masses may require ongoing
imaging in the absence of a definitive diagnosis.

Indications and suitability for


nephron-sparing surgery

For small renal masses, radical nephrectomy should


rarely be performed; nephron-sparing surgery de
livers similar oncologic and superior functional
outcomes; if nephron-sparing surgery would be too
technically complex, a radical nephrectomy can be
performed.

Healthy patient 70 yr of age


The main limitation to probe ablation is the lack of
(because long-term oncorobust long-term oncologic data.
logic data are lacking), tumors >4 cm in diameter (risk
of incomplete tumor ablation), hilar tumors (risk of
injury to renal vessels), uncorrected coagulopathy

Uncorrected coagulopathy, severe renal dysfunction, surgically scarred abdomen


(relative contraindication)

Young, healthy patient

Uncorrected coagulopathy

* Indications for nephron-sparing surgery are absolute (bilateral tumors, a tumor in one kidney, or a poorly functioning or nonfunctioning opposite kidney), relative (renal dysfunction;
hereditary renal-cell carcinoma; a genetic predisposition to metachronous renal-cell carcinoma; systemic threats to future renal function, such as diabetes, hypertension, or nephrotoxic
chemotherapy; or local threats to either kidney, such as obstructive uropathy, stone disease, or renovascular disease), or elective (a small renal mass and a normal opposite kidney).

Elderly, frail patient; important coexisting conditions; poor


surgical risk; limited life expectancy; severely compromised renal function; patient choice of no intervention

Active surveillance

Indications
Known extrarenal or systemic cancer; lobar contour deformity
suggestive of a small renal mass; coexisting conditions
that confer a poor surgical risk; an unresectable mass;
some hyperattenuating masses with homogeneous enhancement or some indeterminate cystic lesions (physicians discretion); suspected focal infection; choice of
young patient; consideration of percutaneous ablation or
neoadjuvant targeted therapy

Needle biopsy

Treatment

Table 1. Treatment Considerations for a Patient with a Small Renal Mass.

clinical pr actice

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

629

The

n e w e ng l a n d j o u r na l

Tumor
Needle driver

Suction
aspirator

Transient,
atraumatic
clamping of the
renal hilum

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 incisional complications, such as flank bulge, discomfort, paresthesias, or hernia.30,31

Cryoablation

Laparoscopic Partial Nephrectomy

Tumor

Cytocidal
temperatures
applied to tumor

An ice ball is created to extend


1 cm beyond the edge of the
tumor circumferentially

phrectomy.25,28 In an observational study comDraft 8


1/19/10
paring partial with radicalAuthor
nephrectomy,
partial
Gill
3
Fig # with
nephrectomy was associated
a significantly
Nephron-sparing therapies
Title
lower risk of renal insufficiency
(12% vs. 22%)
ME
and proteinuria (35% vs. 55%) at the 10-year
DE
Solomon
follow-up.29 In one report,Artist
the risk
Knoper of stage 3 or
AUTHOR
PLEASE
NOTE: after
higher chronic kidney disease
was
20%
Figure has been redrawn and type has been reset
Please check carefully
partial nephrectomy and 65% after
radical nephIssue date 2/18/10
rectomy (P<0.001).26 The observation that metaCOLOR FIGURE

630

m e dic i n e

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 performed by a laparoscopic (Panel A), an open, or a robotic approach.32 The procedure often involves transiently 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 vessels and the collecting system are repaired with sutures
to secure hemostasis and water-tight closure. To minimize ischemic renal injury, the clamp time should be
less than 20 to 30 minutes. Treatment with thermal ablation includes cryoablation (Panel B), which aims to
freeze the entire tumor to 20 to 40C, and radiofrequency ablation, which aims to heat it to 60 to 100C.
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 thermally ablated tumor is not excised but remains in situ.

Laparoscopic partial nephrectomy


Tumor removed along
with overlying
perirenal fat

of

n engl j med 362;7

Minimally invasive nephron-sparing procedures


include laparoscopic or robotic32 partial nephrectomy and image-guided thermal ablation (Fig. 3).
In a large, retrospective, multi-institutional study
comparing outcomes of laparoscopic partial nephrectomy with those of open partial nephrectomy 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 However, the laparoscopic-partial-nephrectomy group
had a longer ischemia time than the open-partial-

nejm.org

february 18, 2010

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

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 unclamping technique during laparoscopic partial
nephrectomy has resulted in lower ischemia
times (mean, 14 minutes) and lower postoperative hemorrhage rates, approximating those reported 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%, respectively) 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 intrarenal, or located in a solitary kidney.37,38 Observational 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.

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 absence of contrast enhancement on CT or MRI.45
Complications have been reported in approximately 10% of patients who have undergone
cryoablation (hemorrhage in 1%, reoperation in
1%, pulmonary complications related to coexisting conditions in approximately 5%, and congestive heart failure related to coexisting conditions in 1%).41 Complications have been reported
in approximately 10% of patients who have undergone radiofrequency ablation (hemorrhage in
1 to 5%, ureteral injury or stricture in 2%, and
severe neuropathic pain in 1.6%).42,43 After thermal ablation, follow-up is empirically recommended at intervals of 6 to 12 months with
dedicated MRI or CT, although data on appropriate 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 UNCER TA IN T Y

Thermal Ablation

Thermal ablation is performed by inserting needle applicators within the renal mass to generate
cytocidal temperatures.39 Cryoablation and radio
frequency ablation are the most common methods and are typically performed after needle biopsy for tissue diagnosis.
Data from a case series of 80 patients who
underwent laparoscopic cryoablation, with a median follow-up of 8 years, indicate that cryoablated 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 undergone previous surgery for metachronous renalcell carcinoma).41 With refinements in probe size
and design, a percutaneous image-guided approach may be preferable to a laparoscopic approach for thermal ablation, since procedureassociated morbidity would be lower.
Initial experiences with percutaneous radio
frequency ablation also indicate favorable short-

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) renal 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. Therefore, the benefit of intervention in the elderly
must be weighed against the risks posed by coexisting conditions.47
The optimal frequency of follow-up imaging
for small renal masses that are monitored without 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-

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

631

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

Single sporadic small renal mass not definitively


benign according to imaging studies

Relatively young patients (<70 yr)


No major coexisting condition
Good life expectancy
Good surgical risk

Elderly patients (70 yr)


Coexisting condition
Limited life expectancy
Compromised renal function
Poor surgical risk

Discuss active surveillance


and thermal ablation
Consider needle biopsy

Preferred option: surgery

Partial nephrectomy
technically feasible

Partial nephrectomy
technically difficult

Laparoscopic or open
partial nephrectomy,
depending on available
surgical expertise

Image-guided ablation
(percutaneous or
laparoscopic)
Cryoablation
Radiofrequency
ablation
Laparoscopic radical
nephrectomy if thermal ablation not safe
or not technically
feasible

Consider needle biopsy


Consider active surveillance
Consider thermal ablation
Preferred option if tumor increases
in size, patient desires
active treatment, or both:
Percutaneous thermal ablation
Cryoablation
Radiofrequency ablation

Figure 4. Suggested Algorithm for Management of a Small Renal Mass.


RETAKE:
1st
AUTHOR: Gill
If the patient is relatively young (<70 years) and healthy, needle biopsy should be considered
and the current litera2nd
FIGURE:
4
of
4
ture about active surveillance and thermal ablation should be discussed with the patient,
even though active surveil3rd
lance is not recommended. Tumor size is an important factor that must beRevised
considered when finalizing the treatment
ARTIST: ts
plan. For example, a spherical 1-cm tumor has a volume of 0.5 ml, whereas aSIZE
4-cm tumor has a volume of 33.5 ml,
6 col
Line
Combo
4-C
H/T
TYPE:
implying considerably greater tumor
burden.
33p9
AUTHOR, PLEASE NOTE:
Figure has been redrawn and type has been reset.
Please check carefully.

biopsy specimens warrants further assessment.


36217
Data from randomized trialsJOB:
comparing
outcomes
of surveillance, surgical interventions, and ablation are lacking to inform treatment recommendations 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.

632

Guidel ine s

ISSUE: 02-18-10

The recommendations proposed in this article


are largely concordant with the 2007 guidelines
of the European Association of Urology for patients with renal-cell carcinoma and the 2009
guidelines of the American Urological Association for patients with a small renal mass.48,49
However, owing to the absence of randomized
trials, these guidelines are based mostly on expert opinion.

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

clinical pr actice

C onclusions a nd
R ec om mendat ions
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 (specifically, partial nephrectomy), given his otherwise

good health. The hilar location of this tumor argues against the use of image-guided ablation,
which can cause thermal injury to the adjacent
renal vessels, the ureter, or both. If partial nephrectomy is performed and pathological studies
confirm the diagnosis of cancer, available data
suggest that this patients chances of survival,
freedom from local recurrence, and preserved renal 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, GlaxoSmithKline,
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.

References
1. Tada S, Yamagishi J, Kobayashi H,

Hata Y, Kobari T. The incidence of simple


renal cyst by computed tomography. Clin
Radiol 1983;34:437-9.
2. Hara AK, Johnson CD, MacCarty RL,
Welch TJ. Incidental extracolonic findings
at CT colonography. Radiology 2000;215:
353-7.
3. Birnbaum BA, Hindman N, Lee J, et al.
Renal cyst pseudoenhancement: influence
of multi-detector CT reconstruction algorithm and scanner type in phantom model.
Radiology 2007;244:767-75.
4. Volpe A, Panzarella T, Rendon RA,
Haider MA, Kondylis FI, Jewett MA. The
natural history of incidentally detected
small renal masses. Cancer 2004;100:73845.
5. Nguyen MM, Gill IS, Ellison LM. The
evolving presentation of renal carcinoma
in the United States: trends from the Surveillance, Epidemiology, and End Results
program. J Urol 2006;176:2397-400.
6. Lee CT, Katz J, Shi W, Thaler HT,
Reuter VE, Russo P. Surgical management
of renal tumors 4 cm. or less in a contemporary cohort. J Urol 2000;163:730-6.
7. Frank I, Blute ML, Cheville JC, Lohse
CM, Weaver AL, Zincke H. Solid renal tumors: an analysis of pathological features
related to tumor size. J Urol 2003;170:221720.
8. Israel GM, Bosniak MA. How I do it:
evaluating renal masses. Radiology 2005;
236:441-50.
9. Silverman SG, Israel GM, Herts BR,
Richie JP. Management of the incidental
renal mass. Radiology 2008;249:16-31.
10. Chawla SN, Crispen PL, Hanlon AL,
Greenberg RE, Chen DY, Uzzo RG. The
natural history of observed enhancing
renal masses: meta-analysis and review of
the world literature. J Urol 2006;175:42531.

11. Siu W, Hafez KS, Johnston WK III,

Wolf JS Jr. Growth rates of renal cell carcinoma and oncocytoma under surveillance are similar. Urol Oncol 2007;25:
115-9.
12. Kunkle DA, Crispen PL, Chen DYT,
Greenberg RE, Uzzo RG. Enhancing renal
masses with zero net growth during active surveillance. J Urol 2007;177:849-54.
13. Remzi M, Ozsoy M, Klingler HC, et al.
Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter.
J Urol 2006;176:896-9.
14. Pahernik S, Ziegler S, Roos F, Melchior SW, Thuroff JW. Small renal tumors:
correlation of clinical and pathological
features with tumor size. J Urol 2007;
178:414-7.
15. Klatte T, Patard JJ, de Martino M, et
al. Tumor size does not predict risk of
metastatic disease or prognosis of small
renal cell carcinomas. J Urol 2008;179:
1719-26.
16. Lee CT, Katz J, Fearn PA, Russo P.
Mode of presentation of renal cell carcinoma provides prognostic information.
Urol Oncol 2002;7:135-40.
17. Nguyen MM, Gill IS. Effect of renal
cancer tumor size on the prevalence of
metastasis at diagnosis and mortality.
J Urol 2009;181:1020-7.
18. Volpe A, Kachura JR, Geddie WR, et
al. Techniques, safety and accuracy of
sampling of renal tumors by fine needle
aspiration and core biopsy. J Urol 2007;
178:379-86.
19. Shannon BA, Cohen RJ, de Bruto H,
Davies RJ. The value of preoperative needle core biopsy for diagnosing benign lesions among small, incidentally detected
renal masses. J Urol 2008;180:1257-61.
20. Rybicki FJ, Shu KM, Cibas ES, Fielding JR, vanSonnenberg E, Silverman SG.

Percutaneous biopsy of renal masses:


sensitivity and negative predictive value
stratified by clinical setting and size of
masses. AJR Am J Roentgenol 2003;180:
1281-7.
21. Barocas DA, Mathew S, DelPizzo JJ, et
al. Renal cell carcinoma sub-typing by
histopathology and fluorescence in situ
hybridization on a needle-biopsy specimen. BJU Int 2007;99:290-5.
22. Volpe A, Jewett MA. The role of surveillance for small renal masses. Nat Clin
Pract Urol 2007;4:2-3.
23. Brenner DJ, Hall EJ. Computed tomography an increasing source of radiation exposure. N Engl J Med 2007;357:
2277-84.
24. Crispen PL, Viterbo R, Fox EB, Greenberg RE, Chen DYT, Uzzo RG. Delayed
intervention of sporadic renal masses undergoing active surveillance. Cancer 2008;
112:1051-7.
25. Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: indications,
techniques and outcomes. J Urol 2001;
166:6-18.
26. Huang WC, Levey AS, Serio AM, et al.
Chronic kidney disease after nephrectomy
in patients with renal cortical tumours: a
retrospective cohort study. Lancet Oncol
2006;7:735-40.
27. Van Poppel H, Da Pozzo L, Albrecht
W, et al. A prospective randomized EORTC
intergroup phase 3 study comparing the
complications of elective nephron-sparing
surgery and radical nephrectomy for lowstage renal cell carcinoma. Eur Urol 2007;
51:1606-15.
28. Fergany AF, Hafez KS, Novick AC.
Long-term results of nephron sparing
surgery for localized renal cell carcinoma:
10-year follow-up. J Urol 2000;163:442-5.
29. Lau WK, Blute ML, Weaver AL, Torres
VE, Zincke H. Matched comparison of

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.

633

clinical pr actice
radical nephrectomy vs nephron-sparing
surgery in patients with unilateral renal
cell carcinoma and a normal contralateral
kidney. Mayo Clin Proc 2000;75:1236-42.
30. Chatterjee S, Nam R, Fleshner N,
Klotz L. Permanent flank bulge is a consequence of flank incision for radical nephrectomy in one half of patients. Urol
Oncol 2004;22:36-9.
31. Yoshimura K, Ohara H, Ichioka K, et
al. Body image alteration after flank incision: relationship between the results of
objective evaluation using computerized
tomography and patient perception. J Urol
2003;169:182-5.
32. Aron M, Koenig P, Kaouk JH, Nguyen
MM, Desai MM, Gill IS. Robotic and laparoscopic partial nephrectomy: a matchedpair comparison from a high-volume
centre. BJU Int 2008;102:86-92.
33. Gill IS, Kavoussi LR, Lane BR, et al.
Comparison of 1,800 laparoscopic and
open partial nephrectomies for single renal tumors. J Urol 2007;178:41-6.
34. Nguyen MM, Gill IS. Halving ische
mia time during laparoscopic partial nephrectomy. J Urol 2008;179:627-32.
35. Gill IS, Kamoi K, Aron M, Desai MM.
800 Laparoscopic partial nephrectomies:
a single surgeon series. J Urol 2010;183:3441.
36. Lane BR, Gill IS. 7-Year oncological

outcomes after laparoscopic and open partial nephrectomy. J Urol 2010;183:473-9.


37. Turna B, Aron M, Gill IS. Expanding
indications for laparoscopic partial nephrectomy. Urology 2008;72:481-7.
38. Richstone L, Montag S, Ost M, Reggio
E, Permpongkosol S, Kavoussi LR. Lapa
roscopic partial nephrectomy for hilar
tumors: evaluation of short-term oncologic outcome. Urology 2008;71:36-40.
39. Goldberg SN, Grassi CJ, Cardella JF, et
al. Image-guided tumor ablation: standardization of terminology and reporting
criteria. Radiology 2005;235:728-39.
40. Gill IS, Remer EM, Hasan WA, et al.
Renal cryoablation: outcome at 3 years.
J Urol 2005;173:1903-7.
41. Aron M, Kamoi K, Remer E, Berger A,
Desai M, Gill IS. Laparoscopic renal cryo
ablation: 8-year, single surgeon outcomes.
J Urol 2010 January 18 (Epub ahead of
print).
42. Gervais DA, McGovern FJ, Arellano
RS, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma.
Part I. Indications, results and role in patient management over a 6 year period
and ablation of 100 tumors. AJR Am J
Roentgenol 2005;185:64-71.
43. Zagoria RJ, Traver MA, Werle DM,
Perini M, Hayasaka S, Clark PE. Oncologic efficacy of CT-guided percutaneous

radiofrequency ablation of renal cell carcinomas. AJR Am J Roentgenol 2007;189:


429-36.
44. Breen DJ, Rutherford EE, Stedman B,
et al. Management of renal tumors by
image-guided radiofrequency ablation:
experience in 105 tumors. Cardiovasc Intervent Radiol 2007;30:936-42.
45. Raman JD, Stern JM, Zeltser I, Kabbani W, Cadeddu JA. Absence of viable
renal carcinoma in biopsies performed
more than 1 year following radio frequency ablation confirms reliability of axial
imaging. J Urol 2008;179:2142-5.
46. Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Rising incidence
of small renal masses: a need to reassess
treatment effect. J Natl Cancer Inst 2006;
98:1331-4.
47. Idem. Five-year survival after surgical
treatment for kidney cancer: a populationbased competing risk analysis. Cancer
2007;109:1763-8.
48. Ljungberg B, Hanbury DC, Kuczyk
MA, et al. Renal cell carcinoma guideline.
Eur Urol 2007;51:1502-10.
49. Campbell SC, Novick AC, Belldegrun
A, et al. Guidelines for management of
the clinical T1 renal mass. J Urol 2009;
182:1271-9.
Copyright 2010 Massachusetts Medical Society.

collections of articles on the journals web site

The Journals Web site (NEJM.org) sorts published articles into


more than 50 distinct clinical collections, which can be used as convenient
entry points to clinical content. In each collection, articles are cited in reverse
chronologic order, with the most recent first.

634

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

The New England Journal of Medicine


Downloaded from nejm.org on June 6, 2011. For personal use only. No other uses without permission.
Copyright 2010 Massachusetts Medical Society. All rights reserved.