Review Articles

Bosniak Classification for Complex Renal Cysts Reevaluated:

A Systematic Review
Ivo G. Schoots,* Keren Zaccai, Myriam G. Hunink† and Paul C. M. S. Verhagen
From the Department of Radiology and Nuclear Medicine (IGS, MGH), Urology (KZ, PCMSV) and Epidemiology (MGH),
Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands, and Harvard School of Public Health,
Harvard University, Department of Health Policy and Management, Boston, Massachusetts (MGH)

Purpose: We systematically evaluated the Bosniak classification system with

Abbreviations
and Acronyms
CEUS ¼ contrast enhanced
ultrasound
CT ¼ computerized tomography
MRI ¼ magnetic resonance
imaging
NNT ¼ number needed to treat
QUADAS-2 ¼ Quality Assessment
of Diagnostic Accuracy Studies
RCC ¼ renal cell carcinoma
Accepted for publication September 19, 2016.
No direct or indirect commercial incentive
associated with publishing this article.
The corresponding author certifies that, when
applicable, a statement(s) has been included in
the manuscript documenting institutional review
board, ethics committee or ethical review board
study approval; principles of Helsinki Declaration
were followed in lieu of formal ethics committee
approval; institutional animal care and use
committee approval; all human subjects provided
written informed consent with guarantees of
confidentiality; IRB approved protocol number;
animal approved project number.
* Correspondence: Department of Radiology
and Nuclear Medicine, Erasmus MC University
Medical Centre, P.O. Box 2040, ’s Gravendijkwal
230, 3000 CA, Rotterdam, The Netherlands
(e-mail: i.schoots@erasmusmc.nl).
† Financial interest and/or other relationship
with European Institute for Biomedical Imaging
Research, European Society of Radiology and
Cambridge University Press.
malignancy rates of each Bosniak category, and assessed the effectiveness related
to surgical treatment and oncologic outcome based on recurrence and/or metastasis.
Materials and Methods: In a systematic review according to PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-Analyses) statement and the
QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria, we
selected 39 publications for inclusion in this analysis and categorized them into
1) surgical cohortsdall cysts treated surgically and 2) radiological cohortsdcysts
with surgical treatment or radiological followup.
Results: A total of 3,036 complex renal cysts were categorized into Bosniak II,
IIF, III and IV. In surgical and radiological cohorts pooled estimates showed a
malignancy prevalence of 0.51 (0.44, 0.58) in Bosniak III and 0.89 (0.83, 0.92) in
Bosniak IV cysts, respectively. Stable Bosniak IIF cysts showed a malignancy
rate of less than 1% during radiological followup (surveillance). Bosniak IIF
cysts, which showed reclassification to the Bosniak III/IV category during
radiological followup (12%), showed malignancy in 85%, comparable to Bosniak
IV cysts. The estimated surgical number needed to treat to avoid metastatic
disease of Bosniak III and IV cysts was 140 and 40, respectively.
Conclusions: The effectiveness of the Bosniak classification system for complex
renal cysts was high in categories II, IIF and IV, but low in category III, and 49%
of Bosniak III cysts was overtreated because of a benign outcome. This surgical
overtreatment combined with the excellent outcome for Bosniak III cysts may
suggest that surveillance is a rational alternative to surgery. This will require
further study to assess whether surveillance of Bosniak III cysts will prove safe.
Key Words: kidney, cysts, classification, treatment outcome,
numbers needed to treat
IN 1986 Bosniak proposed a classifi- classification was the first to connect
cation of renal cysts, distinguishing radiological findings to treatment
categories from I to IV. The diagnosis advice. Complex renal cysts catego-
and management of complex renal rized as Bosniak III and IV were ex-
cysts were contentious, and a combi- pected to be malignant lesions, and
nation of CT, ultrasound and urog- resection was recommended. This
raphy was used to distinguish classification was fully embraced by
between benign and malignant cystic international urology and radiological
renal lesions. The Bosniak societies, and implemented into

0022-5347/17/1981-0012/0 http://dx.doi.org/10.1016/j.juro.2016.09.160

12 j www.jurology.com
THE JOURNAL OF UROLOGY®
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Printed in U.S.A.
 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS
guidelines. To date competing systems have not
been published.
In recent decades the Bosniak classification has
been modified and has influenced clinical practice.
The most important modifications include the
introduction of Bosniak category IIF in 1993, to
bridge category II and III with the option of radio-
logical followup, and the decreased importance of
nodular calcifications in 2003,1 which qualify a
lesion to category II or IIF instead of class III.
Furthermore, the original classification in 1986 was
based on CT. The technique of CT has evolved over
the years, which implies that current CT shows
details that were not visible in 1986. New imaging
modalities such as MRI and CEUS have become
available and may contribute to the current Bosniak
classification system (fig. 1).
The Bosniak classification system has been dis-
cussed in many reviews. However, to our knowl-
edge no systematic review has been conducted. We
systematically reviewed the published literature
on the Bosniak classification for renal cysts. We
performed this review 1) to assess malignancy risk
in the different Bosniak categories and 2) to assess
long-term oncologic outcome of patients treated in
concordance with this system, based on radiolog-
ical recurrence and metastatic disease. We also
collected evidence on interobserver variability
among radiologists using the Bosniak classification
Figure 1. Bosniak classification system. Drawing courtesy of Dr. Matt Skalski, Radiopaedia.org, rID: 20989 (with permission).
13
system. The combination of these data should
allow us to evaluate the effectiveness (clinical
value) of this classification system in the different
Bosniak categories.
The Bosniak system may be safe from an onco-
logic point of view. However, to date, considerable
surgical overtreatment in Bosniak category IIF and
III has been regarded as inevitable and, therefore,
acceptable. In this review we estimate the amount
of overtreatment and risks related to complex renal
cysts, and question whether active surveillance of
Bosniak III complex renal cysts could be a reason-
able alternative to surgery.
METHODS
Objective
We systematically evaluated the Bosniak renal cyst clas-
sification introduced by Morton A. Bosniak with the
intention of establishing the effectiveness (clinical value),
based on malignancy rates of the Bosniak categories,
combined with oncologic outcome.
Search Strategy
The search strategy is provided in the supplementary
Appendix (http://jurology.com/). In summary, for each
database the search terms used were kidney cyst, kidney*,
renal or nephro*, in relation to cyst, cystic or cysts, and in
combination with complex, complicated or multiloc*.
Furthermore, the search terms bosniak, bosniac, bosniack
14 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS

and classification or diagnostic accuracy were used. The
search was limited to humans and adults. A critical review of
Embase, MEDLINEÒ (OvidSP), Web of ScienceÔ, PubMedÒ
publisher, Google ScholarÔ and the Cochrane library was
performed. The search was updated to August 12, 2016.
Inclusion and Exclusion Criteria
The included studies all focus on adults with complex
renal cysts categorized by the Bosniak classification sys-
tem (fig. 1). We selected only studies with imaging eval-
uation by CT or magnetic resonance according to the
Bosniak classification, combined with surgical resection
and histopathology analysis.
Reports with patient selection based on malignancy in
pathology databases were excluded from study. In these
reports all cystic masses were malignant, thereby over-
estimating the malignancy rate in the Bosniak categories.
Furthermore, duplicates and reports with a reference
standard of histopathology analysis from percutaneous
biopsies only were also excluded. Reports with imaging
evaluation by CEUS only or no sufficient data available
were excluded. Unpublished data or abstracts were
excluded from study because information that is needed to
correctly assess the study quality (QUADAS-2) and
interpret the results was not available in the abstracts.
The index test was defined as CT or MRI for catego-
rizing complex renal cysts by the Bosniak classification
system. The reference test was defined as histopatholog-
ical analysis of surgically resected complex renal cysts. A
positive reference test was defined by malignancy.
Data Collection and Data Extraction
The PRISMA process for reporting included and excluded
studies was followed, with the recommended flowchart
showing the numbers of studies identified and included or
excluded at each stage (fig. 2). Titles and abstracts were
reviewed for relevance to the defined review question.
The references cited in all full text articles were also
assessed for additional relevant articles. The search was
performed by 3 reviewers (IS, KZ, PV), independently.
Discrepancies among the reviewers were resolved via
discussion.
Data regarding study methodology, patient population,
conduct of imaging and outcomes were extracted. We
identified 2 categories of published reports, namely
1) surgical cohorts of complex renal cysts, in which all
were treated surgically and 2) radiological cohorts of
complex renal cysts, in which some of the cysts had
radiological followup instead of surgery. In the category of
surgical reports, studies before and after the introduction
of the Bosniak IIF in 1993 were identified. In the category
of radiological reports only studies after the introduction
of Bosniak IIF were encountered. Identified reports
were reviewed according to the QUADAS-2 instrument
(supplementary Appendix, http://jurology.com/).
Data Synthesis and Analysis
To synthesize the results we performed a random effects
meta-analysis using generalized linear mixed models for
single arm studies on the malignancy prevalence of
Bosniak categories II, IIF, III and IV as well as the
category of Bosniak IIF cysts reclassified to III/IV. Het-
erogeneity was assessed using the chi-square statistic
and the I2 statistic. Construction of 95% confidence in-
tervals was done with the Wilson score interval. A con-
tinuity correction was applied where necessary. Analyses
were performed using R Statistical Software (version
3.2.1, R Foundation for Statistical Computing, Vienna,

7259 records idenfied

(Embase.com 3057, Medline (OvidSP) 2414, Web-of-Science 1580,
Cochrane 8, Google Scholar 200)

2932duplicate records

4327 unique records

4096 records excluded: not related to research queson

231 records for full text review

170 reports excluded: not related to research queson

3 reports excluded : only malignant cysts selected from pathology database

3 report excluded: no substanal data available

2 reports excluded: only CEUS imaging data available

3 reports excluded: studies: histopathology only from biopsy (no surgery)

1 report excluded: duplicates data

10 reports excluded: unique abstracts, no full paper

39 reports on complex renal cysts, categorized by the Bosniak classificaon,

with surgical histopathology as reference

Figure 2. PRISMA flow diagram showing outcome of searches resulting in full studies included in review
 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS
Austria). The meta-analysis was performed using the
metafor package.
RESULTS AND DISCUSSION
A total of 39 studies were eligible for inclusion in
this review (table 1).1e39 Supplementary table 1
(http://jurology.com/) shows individual data on
outcome results. A summary analysis is presented
in table 2. Additional data on methodology, patient
population, and imaging are presented in
supplementary table 2 (http://jurology.com/).
Publication Bias and Study Quality
None of the individual studies explicitly followed
the STARD guidelines for diagnostic studies. A
summary of the results of the QUADAS-2 assess-
ment for all included studies is presented in
figure 3. According to the QUADAS-2 criteria we
concluded that the overall quality of the studies was
poor, with a high risk of bias and concerns about
applicability, which limits the strengths of the con-
clusions that can be made. A detailed description of
signaling questions, assessment of study quality
and additional explanations are available in the
supplementary Appendix (http://jurology.com/).
Selection bias was present in all studies. Surgical
cohorts only reported the complex renal cysts that
were surgically resected. Radiological cohorts only
reported complex renal cysts detected by CT or MRI,
as these imaging modalities can accurately catego-
rize cysts. Prospective and consecutive series were
absent. Test review bias may occur when interpre-
tation of the results of the index test may be influ-
enced by the knowledge of the results of the
reference standard (histopathology analysis after
surgical resection), and this was not reported.
The index test was defined by renal cyst imaging
by CT or magnetic resonance. The definition of
prespecification of the threshold of the index test
was set by the Bosniak classification system of renal
complex cysts. Results may differ between the 2
imaging modalities. In addition, various CT and
magnetic resonance protocols were used. In some
studies additional information was obtained using
ultrasound or CEUS (see supplementary Appendix,
http://jurology.com/).
Interobserver Variability
We evaluated interobserver variability among
radiologists by using the (weighted) Cohen’s kappa
and agreement percentages. The interobserver
variability of the Bosniak classification system was
reported in 8 studies (table 2).5,15,28,33,40e43 Cohen’s
kappa values as a measure of variability ranged
from 0.57 to 0.98 (moderate to very good). Moderate,
good and very good agreements were scored in 2, 3
and 1 of 6 reports, respectively. The value of kappa
15
in interobserver variability reports is divided into
the 4 categories of fair (0.21 to 0.40), moderate (0.41
to 0.60), good (0.61 to 0.80) and very good (0.81 to
1.00). Despite reasonable kappa values in the eval-
uated studies a large range of disagreement is re-
ported among observers, ranging from 6% to 75%,
especially in categories II, IIF and III (table 3). The
extreme Bosniak categories (I and IV) are easier for
radiologists to categorize, which leads to reasonable
kappa values, whereas considerable disagreement
remains among the categories in between. Some
studies report on separate variables such as the
presence or absence of enhancing septum or cyst
wall rather than reporting on the Bosniak classifi-
cation, which showed better agreement.40,42 Finally,
we may conclude that the interobserver variability
for Bosniak categories II, IIF and III is large for a
clinical imaging test, as demonstrated by a
disagreement of up to 75%. This underscores the
clinical need to develop a more robust system to
identify patients in whom surgical treatment is
necessary and in whom overtreatment is limited.
Prevalence of Malignancy in Complex Renal Cysts
This review comprised a total of 3,036 complex renal
cysts, categorized into Bosniak II, IIF, III and IV
(supplementary table 1, http://jurology.com/). Before
the introduction of the Bosniak category IIF, in sur-
gical cohorts pooled data of 329 complex renal cysts
showed a malignancy prevalence of 0.08 (0.04, 0.15),
0.46 (0.23, 0.71) and 0.93 (0.66, 0.99) in Bosniak
categories II, III and IV, respectively. In surgical
cohorts after the introduction of the Bosniak cate-
gory IIF, pooled data of 972 complex renal cysts
revealed a malignancy prevalence of 0.09 (0.05, 0.14),
0.18 (0.12, 0.26), 0.51 (0.42, 0.61) and 0.86 (0.81, 0.89)
in Bosniak categories II, IIF, III and IV, respectively
(table 2 and supplementary table 1, http://jurology.
com/). In radiological cohorts after the introduction
of the Bosniak category IIF, accumulated data of
1,735 complex renal cysts showed a malignancy
prevalence of 0.54 (0.45, 0.63) and 0.95 (0.79, 0.99) in
Bosniak categories III and IV, respectively. Bosniak
categories III and IV did not show a significantly
different malignancy prevalence between surgical
and radiological cohorts (table 2 and supplementary
table 1, http://jurology.com/).
Pooled Bosniak II malignancy data are not pre-
sent in radiological cohorts because complex renal
cysts in this category were not treated with surgical
resection or followup. The malignancy prevalence of
Bosniak IIF is also more difficult to extrapolate in
radiological cohorts. From the 954 Bosniak IIF cysts
(without increase in Bosniak category during fol-
lowup) less than 1% (9 of 954) were malignant
following resection in 54 cases. In these resected IIF
cysts the malignancy prevalence was comparable to
Table 1. Data from 39 publications eligible for study inclusion

16
Bosniak II (351) Bosniak IIF (1,074) Reclassified Bosniak IIF to III/IV (77) Bosniak III (1,001) Bosniak IV (527)

Total Complex No. No. Malignant No. No. Malignant No. Reclassified No. Malignant No. No. Malignant No. No. Malignant
References Cysts (3,036) Cysts Cysts/Resections Ratio Cysts Cysts/Resections Ratio Cysts/All IIF Ratio Cysts/Resections Ratio Cysts Cysts/Resections Ratio Cysts Cysts/Resections Ratio

Surgical cohorts
Reports without Bosniak IIF:
Aronson et al2 16 4 0/4 0.00 e e e e e e e 7 4/7 0.57 5 5/5 1.00
Bellman et al3 10 5 0/5 0.00 e e e e e e e 5 0/5 0.00 e e e
Cloix et al4 30 7 1/7 0.14 e e e e e e e 13 4/13 0.31 10 7/10 0.70
Siegel et al5 48 8 1/8 0.13 e e e e e e e 11 5/11 0.45 29 26/29 0.90
Balci et al6 46 18 0/18 0.00 e e e e 3 0/3 0.00 25 14/25 0.56
Bielsa Gali et al7 20 8 1/8 0.13 e e e e e e e 9 7/9 0.78 3 3/3 1.00

OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS

Curry et al8 78 11 0/11 0.00 e e e e e e e 49 29/49 0.59 18 18/18 1.00
Koga et al9 24 2 1/2 0.50 e e e e e e e 10 10/10 1.00 12 12/12 1.00
Limb et al10 57 28 3/28 0.11 e e e e e e e 29 8/29 0.28 e e e

Overall 329 91 7/91 0.08 e e e e e e 136 67/136 0.46 102 85/102 0.93
Reports with Bosniak IIF:
Spaliviero et al11 46 9 2/9 0.22 4 1/4 0.25 e e e e 12 6/12 0.50 21 19/21 0.91
Loock et al12 37 6 0/6 0.00 10 2/10 0.20 e e e e 14 3/14 0.21 7 6/7 0.86
Kostiukov et al13 25 e e e e e e e e e e 21 8/21 0.38 4 3/4 0.75
Song et al14 104 26 3/26 0.12 3 0/3 0.00 e e e e 38 21/38 0.55 37 32/37 0.87
Kim et al15 91 22 3/22 0.14 10 3/10 0.30 e e e e 26 19/26 0.73 33 28/33 0.85
Pinheiro et al16 37 e e e e e e e e e e 15 5/15 0.33 22 19/22 0.86
Han et al17 98 9 0/9 0.00 18 3/18 0.17 e e e e 39 21/39 0.54 32 29/32 0.91
Mei et al19 52 24 1/24 0.04 28 4/28 0.14 e e e e e e e e e e
Goenka et al18 107 e e e e e e e e e e 107 59/107 0.55 e e e
Bata et al20 19 e e e e e e e e e e 19 16/19 0.84 e e e
Reese et al21 113 16 2/16 0.14 6 2/6 0.33 e e e e 32 21/32 0.66 59 50/59 0.85
Boulma et al39 22 e e e e e e e e e 10 3/10 0.30 12 11/12 0.92
Oh and Seo38 221 53 2/53 0.04 41 7/41 0.17 e e e e 71 27/71 0.38 56 46/56 0.82

Overall 972 165 15/165 0.09 120 22/120 0.18 e e e e 404 209/404 0.51 283 243/283 0.86
Radiological cohorts
Reports all with Bosniak IIF:
Israel and Bosniak1,* 81 21 0/0 e 19 0/3 0.00 e e e e 25 9/21 0.43 16 16/16 1.00
Israel and Bosniak22,* 42 e e e 39 0/0 e - e 2/3 0.67 e e e e e e
Ascenti et al23 44 24 0/0 e 10 0/0 e e e e e 7 3/6 0.50 3 3/3 1.00
Clevert et al24 38 15 0/0 e 8 0/1 0.00 e e e e 8 3/6 0.50 7 7/7 1.00
Quaia et al25 40 3 0/0 e 6 0/0 e e e e e 13 3/12 0.25 18 18/18 1.00
Gabr et al26 50 e e e 43 0/0 e 7/50 0.14 5/7 0.71 e e e e e e
O’Malley et al27 112 e e e 69 0/0 e 12/81 0.15 5/5 1.00 31 22/28 0.79 e e e
Weibl et al28,† 113 26 0/2 0.00 15 2/3 0.67 e e e e 28 15/27 0.56 44 30/39 0.77
Hwang et al29,‡ 215 e e e 201 0/23 0.00 14/215 0.07 10/12 0.83 e e e e e e
Smith et al30 213 e e e 69 4/16 0.25 e e e e 144 58/107 0.54 e e e
Elmussareh et al31 42 e e e 41 0/0 e 1/42 0.02 0/0 e e e e e e e
Graumann et al32 44 e e e 39 0/0 e 5/44 0.11 2/3 0.67 e e e e - e
El-Mokadem et al33 134 e e e 68 0/0 e 10/78 0.13 7/8 0.88 31 10/16 0.63 25 12/14 0.86
Hindman et al34 156 e e e 137 0/0 e 19/156 0.11 17/19 0.89 e e e e e e
Smith et al35 293 e e e 159 3/8 0.38 e e e e 112 29/72 0.40 22 18/20 0.90
Weibl et al36 85 e e e 18 0/0 e 9/27 0.33 8/9 0.89 58 37/54 0.69 e e e
Ferreira et al37 33 9 0/0 e 13 0/0 e e e e e 4 2/4 0.50 7 7/7 1.00

Overall 1,735 95 Not Not 954 9/54 0.14 77/693 0.12 54/63 0.85 461 191/353 0.54 142 111/124 0.95
applicable applicable

* Chance of partially double publication (as a result of recruitment dates) with Hindman et al.34
† Chance of partially double publication (as a result of recruitment dates) with Weibl et al.36
‡ Chance of partially double publication (as a result of recruitment dates) with Han et al.17
 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS 17

that in surgical cohorts at 0.14 (0.03, 0.50) vs 0.18

16.6 (0.020)
26.1 (0.000)
2.5 (0.981)

47.1 (0.003)
Chi-square
I2 (%) (p value)
(0.12, 0.26), respectively. We do not have additional
information on why these 54 cysts were resected,
Bosniak IV (509)

* Overestimation of malignancy prevalence is likely. Ratio is based only on series with histopathology of surgically resected cysts. Radiological followup of Boniak II and IIF renal cysts was not included in these data.
but remarkably in these studies no increase from a

58
80
0

45
Bosniak IIF to Bosniak III/IV cyst was reported
during followup. This suggests a malignancy over-

23.3 (0.010) 0.95 (0.79, 0.99)

37.8 (0.000) 0.93 (0.66, 0.99)
33.5 (0.000) 0.86 (0.81, 0.89)

95.6 (0.000) 0.89 (0.83, 0.92)

Chi-square Pooled Estimate
(95% CI) estimation of the IIF category by focusing only on
the resected IIF cysts. The malignancy prevalence
of the entire Bosniak IIF category would be more
likely to be less than 1%.
During radiological followup 0.12 (0.08, 0.17) of
I2 (%) (p value)

the Bosniak IIF complex renal cysts were reclassi-

fied to Bosniak III/IV (supplementary table 1, http://
Bosniak III (893)

jurology.com/). Among these radiologically reclassi-

55
70
83
68

fied cysts 0.85 (0.74, 0.92) were malignant after

resection. Therefore, substantial change within a
4.2 (0.754) 0.54 (0.45, 0.63)
4.2 (0.754) 0.51 (0.44, 0.58)
0.46 (0.23, 0.71)
0.51 (0.42, 0.61)
Chi-square Pooled Estimate
(95% CI)

complex renal cyst originally categorized as Bosniak

IIF, resulting in reclassification to Bosniak III/IV,
has a high positive predictive value for malignancy.
The group categorized as Bosniak IV showed a
Reclassified Bosniak IIFeIII/IV (66)

I2 (%) (p value)

positive predictive value of 0.89 (0.83, 0.92), which

e
e

is quite acceptable for selecting patients for

surgery (table 2 and supplementary table 1, http://
jurology.com).
e
e

0
0

The Bosniak III category demonstrated a positive

16.3 (0.006) 0.85 (0.74, 0.92)
19.6 (0.104) 0.85 (0.74, 0.92)
Chi-square Pooled Estimate

predictive value of 0.51 (0.44, 0.58) (table 2). In other

(95% CI)

words, 49% have been operated on for a benign renal

e
e

cyst. Considerable surgical overtreatment in the

Bosniak III category has been regarded as inevitable
3.3 (0.855)

and, therefore, acceptable. However, we should

I2 (%) (p value)

question whether active surveillance of Bosniak III

e

could be a reasonable alternative to surgery.

Bosniak IIF (174)

Data on changes in Bosniak III complex renal

70
0

7
e

cysts are not available. However, as change within a

Bosniak IIF complex cyst has proven to be helpful in
0.14 (0.03, 0.50)*
7.3 (0.291) 0.18 (0.12, 0.26)*

17.1 (0.313) 0.18 (0.13, 0.25)*

Pooled Estimate

distinguishing malignant from benign, would

(95% CI)

change within a Bosniak III cyst also be helpful to

e

distinguish malignant from benign? In addition, we

anticipate more consistency in the selection of
patients for surgery because we assume it is easier
9.7 (0.285)
Chi-square
Table 2. Malignancy prevalence in complex renal cysts

(p value)

to assess change accurately in a complicated cyst on

e

repeat CT than it is to assess Bosniak category

Bosniak II (232)

without previous imaging.

I2 (%)

e
0
0

Oncologic Outcome of Complex Renal Cysts

Reports without Bosniak IIF 0.08 (0.04, 0.15)*
0.09 (0.05, 0.14)*

0.09 (0.05, 0.12)*

Pooled Estimate

The clinical use of active surveillance depends on

(95% CI)

the oncologic outcome, based on the chance of pro-

e

gression and metastasis. In addition to the main

outcome (prevalence of malignancy in complex renal
cysts), data from the included studies were collected
Reports all with Bosniak IIF
Reports with Bosniak IIF

to evaluate the oncologic outcome of complex renal

cysts based on local recurrence, metastasis or dis-
Radiological cohorts:

ease related death (supplementary table 3, http://

Combined cohorts
Surgical cohorts:

jurology.com/). Only 13 of 39 included studies

included some information on followup and clinical
outcome. A total of 1,535 complex cysts were
collected with a prevalence of malignancy of 24%
18 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS

Figure 3. Summary of results of QUADAS-2 assessment for all included studies

(373 of 1,535) in these series. Of the 373 malignant
cysts 88% was categorized as Bosniak III and IV.
In this review we identified 5 of 373 (1.3%)
patients with local recurrence within a followup of
31 months (estimated average), all having a Bos-
niak III or IV renal cyst (supplementary table 3,
http://jurology.com/). All local recurrences were
re-treated and no patients died of disease progres-
sion during followup. Additional information on
initial positive resection margins or fluid spill dur-
ing surgical resection was not available.
In the selected reports 3 of 373 (0.8%) patients
had metastatic disease during initial presentation
(Bosniak III/IV). Metastatic disease developed in
only 1 of 373 (0.2%) patients during followup (Bos-
niak III). This patient, with a history of a solid renal
cell carcinoma, experienced local tumor progression
and metastatic disease after thermal ablation of a
Bosniak III renal cyst that grew during an 8-year
period of observation, triggering a change in man-
agement and thermal ablation of the cyst. Three
years after subsequent thermal ablation and oligo-
metastasectomy of the lung metastasis, the patient
was alive and had no apparent disease.35
The exact characteristics of complex renal cysts
(ie Bosniak category, histological type and grading,
lesion size) may affect prognosis. However, only
limited data could be extracted from the included
reports. Several reports on cystic RCC show the low
risk of local progression or metastases when
managed according to the Bosniak system.16,44,45
A risk ratio of 0.06 to die of clear cell RCC with a
cystic architecture was reported compared to solid
RCC.46 In selected reports in this review almost two-
thirds (63%) of the malignant complex renal
cysts appear to be a cystic clear cell RCC and the
other third is a heterogeneous group of malignancies
(supplementary table 3, http://jurology.com/).
Furthermore, multilocular cystic RCC, a subtype of
clear cell RCC, is reported to account for 10% to 30% of
cystic renal cancers.27,30,45 This entity is now regar-
ded as a tumor of low malignant potential since
metastases have rarely been reported.44
In this review approximately a quarter of the
cystic clear cell RCC counts for multilocular
cystic RCC (supplementary table 3, http://jurology.
com/).27,30,35 During a followup of 31 months the
oncologic outcome of Bosniak III/IV in this review
was good with only 1% (4 of 373) of metastatic
disease at presentation (0.8%) or during surveil-
lance (0.2%). Although imaging is currently not
able to select only those Bosniak III cysts which
are safe to observe, the substantial number of
clear cell RCCs and the subtype multilocular cystic
RCC in complex renal cysts, together with a good
prognostic outcome, may support surveillance in
this category, or at least may support restraint in
proceeding to immediate surgical resection.

Table 3. Studies on interobserver variability (kappa) among radiologists

Bosniak
No. No. No. Agree
References Observers Total Cysts I II IIF III IV Benign Malignant (%) Kappa
5
Siegel et al 3 70 22 8 e 11 29 38 32 59* 0.57
Siegel et al40 3 69 20 e e e e e e 93† e
Benjaminov et al41 2 32 e 0e5 2e7 8e13 12e17 11 21 50 0.52‡
Bertolotto et al42 2 70 e 18e23 26e27 12e17 8e9 8§ 15§ e 0.64‡
Kim et al15 2 125 30e34 22e32 10e13 24e26 26e33 72 53 61 0.70
Weibl et al28 2 71 e 7e25 3e12 5e8 3e26 25 46 25e88 e
El-Mokadem et al33 2 96 e 8e13 50e53 21e28 7e12 9§ 29§ 70 0.69‡
Graumann et al43 3 100 18e19 16e27 6e13 9e19 17e22 e e 66e94k 0.85e0.98‡

* Overall 41% disagreement, with 11% disagreement on category I or II vs category III or IV, thus with consequences for therapy.
† Agreement reported only on presence or absence of enhancement (cutoff in protocol 15 HU).
‡ Weighted kappa.
§ Histology available in part of cysts only.
k Agreement with consensus classification (performed by the same observers).
 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS
Surveillance in Complex Renal Cysts
While applying the Bosniak classification system is
safe from an oncologic point of view, the presented
results raise the question of whether a more conser-
vative approach is appropriate in certain cases. Sur-
veillance in Bosniak IIF is effective, considering
that this systematic review revealed not a single
patient in whom metastases or local recurrences were
identified after surveillance or delayed resection.
The oncologic outcome of resection of Bosniak III
and IV lesions is also good and immediate surgery
might not be necessary in selected patients. The
Bosniak classification, introduced in the late 80s,
focused on the detection of malignancy in complex
renal cysts. If the primary outcome were malig-
nancy, the number needed to treat (surgically) in
Bosniak categories III and IV is 1.92 and 1.11,
respectively (table 4).
From this standpoint the diagnostic pathway with
the Bosniak classification system is solid. However,
if the primary outcome for the Bosniak III category
would be the avoidance of metastatic disease on top
of malignancy (positive predictive value of 0.013,
table 3), the estimated NNT would be 140. In this
calculation metastatic disease at initial presentation
is also included, which might even underestimate
the NNT. Nevertheless, this number should be
considered a large degree of surgical overtreatment
in the Bosniak III category, and may support an
approach of active surveillance. For the Bosniak IV
category the estimated NNT to avoid metastatic
disease is 40, based on the higher positive predictive
values of malignancy and metastatic disease.
Obviously oncologic surveillance data of Bosniak
III cysts are lacking. Although the presented onco-
logic outcome of Bosniak III cysts shows a very low
risk of metastasis, it will require further study to see
if surveillance of Bosniak III cysts will prove safe.
Disadvantages of Surgery or Surveillance
These NNTs should also be considered in light of the
number of complications and loss of kidney function
associated with surgical resection. Only 2 recent
studies reported details on the type of surgery for
Bosniak III or IV renal cysts. Weibl et al reported
partial and total nephrectomy for Bosniak III cysts in
Table 4. NNT of Bosniak III and IV renal cysts considering outcome of malignant cysts or metastatic disease if malignant
Outcome
Bosniak III
Combined cohorts 467/893
Pos predictive value 0.51 (0.44, 0.58)
NNT 1.96
* Some complex renal cysts were not discriminated in Bosniak
overestimate NNT. For local recurrence and metastatic disease
† Some complex renal cysts were not discriminated in Bosniak
overestimate NNT. For local recurrence and metastatic disease
19
37 of 54 (69%) and 17 of 54 (31%), respectively.36
Smith et al reported partial and total nephrectomy
in 50 of 86 (58%) and 36 of 86 (42%),35 with no distinc-
tion between Bosniak III and Bosniak IV. These
numbers of total nephrectomies underscore overtreat-
ment and the need for better surgical selection.
Smith et al described the complications associated
with surgery.35 They reported moderate to severe
complications in 19% of patients treated with surgery
and 0% of patients who underwent imaging surveil-
lance. Severe complications (Clavien grade 4a)
related to the management of Bosniak renal cysts
occurred in 7% of surgical cases, and included mul-
tiorgan failure, acute myocardial infarction, conver-
sion to hemodialysis dependent chronic kidney
disease, acute ischemic stroke and severe post-
operative hemorrhage. This may support active sur-
veillance of the Bosniak III category to reduce the
number of moderate and severe complications
related to surgical resection. However, we acknowl-
edge the associated downsides of surveillance such as
cost, exposure to x-rays, risk of noncompliance and
psychological stress, which should be investigated in
the long term. A more liberal use of surveillance must
be restricted to patients informed about the advan-
tages and disadvantages of all options.
Role of Biopsy
Only limited information is available on the role of
biopsy in cystic renal lesions. Some reports showed
correct identification of malignancy in the majority of
complex renal cysts (60% to 70%), with low inadequate
sampling (10%) and misdiagnosis (2%).47 However, if
a biopsy result is negative, can this negative result be
trusted? This is also a concern in solid renal lesions.
Biopsies of solid renal masses during surgical resec-
tion showed nondiagnostic rates of 11% to 17%, a
sensitivity of 77% to 84% and specificity of 60% to
73%.48 For cystic lesions biopsied in vivo these figures
are expected to be worse.
Another drawback of performing a biopsy of a
complex cyst is the resulting change of aspect of the
cystic lesion, which will interfere with the inter-
pretation of repeat imaging. This review shows that
the surveillance strategy in cases with a low
malignancy risk (Bosniak IIF) is successful and
Malignant Metastatic Disease
IV III/IV III IV
439/509 4/330 3/224* 3/106†
0.89 (0.83, 0.92) 0.012 0.013 0.028
1.12 e 140 40
III or IV, and were added to this group, suspected to be a Bosniak III cyst to underestimate rather than
this was 1 and 2 cysts, respectively.
III or IV, and were added to this group, suspected to be a Bosniak IV cyst to underestimate rather than
this was 1 and 2 cysts, respectively.
20 OUTCOMES MAY SUPPORT SURVEILLANCE OF BOSNIAK III CYSTS
cannot easily be improved by an invasive procedure.
Therefore, we believe that the use of biopsies will
remain limited in the diagnosis of complex renal
cysts, although it may be helpful in selected cases.
Size of Complex Renal Cysts
Lesion size is related to risk of progression in solid
and cystic RCC. In solid RCC the 10-year cancer
specific survival for T1a renal lesions (smaller than 4
cm) is approximately 96% and, thus, 4% will have
died of cancer within 10 years.49 The relative risk of
death from a clear cell RCC with cystic architecture is
0.06, as previously mentioned.46 This could be
extrapolated to a 0.2% (4% * 0.06) risk of death from a
Bosniak III and IV cyst smaller than 4 cm. From a
large retrospective database of patients who
underwent surgical resection for cystic RCC,
regardless of size, the cancer specific mortality was
1.8%.50 This estimate is in agreement with the low
numbers of metastatic disease in Bosniak III/IV (4 of
330, 1.2%) we found in this systematic review,
regardless of lesion size (average ranging from 2.8 to
5.6 cm, supplementary table 3, http://jurology.com/).
The criteria for size selection cannot be defined on the
basis of this review. However, size should be consid-
ered in surveillance of renal cysts, as small renal
lesions are more indolent than large renal lesions,
just as cystic lesions are more indolent than solid
lesions.
Surveillance Schemes
Several surveillance schemes for Bosniak IIF renal
cysts has been recommended with an initial 4 to
6-month interval and a total duration of 5 years,
which has been proven effective. Several patient
related factors (anatomical location of the cyst, body
weight, kidney function, allergies, exposure to
irradiation and claustrophobia) may influence the
choice of the optimal imaging technique during
surveillance. At present, recommendations on sur-
veillance schemes can only be made based on
assumptions, and the disadvantages of surveillance
should be included and weighed on a patient basis.
Limitations and Strengths
Adjustments to the Bosniak system since its first
publication in 1986, the use of alternative imaging
modalities to CT (MRI and CEUS) and the lack of
prospective trials have made systematic analysis
of complex renal cysts challenging. Nevertheless,
we believe that valuable information on this topic
has been published and that this review allows
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