UROLOGICAL ONCOLOGY
Determination of the Safe Surgical Margin for T1b Renal Cell Carcinoma
Kan Zhang, Wen Lian Xie*
Purpose: To determine the rational surgical margin for pathological T1b renal cell carcinoma (RCC).
Materials and Methods: This retrospective study included surveys of 60 patients with T1bN0M0 RCC who un-
derwent radical nephrectomy (RN, n = 40) or partial nephrectomy (PN, n = 20) between October 2008 and Decem-
ber 2014 at the Sun Yat-sen Memorial Hospital affiliated with Zhongshan University. Specimens were collected
from 6 sites at the tumour periphery for RN and PN, and at suspected sites on the tumour surface for PN in addition.
The histological subtype, pathological grade, surgical margin, pseudocapsule completeness, distribution of satellite
foci, and largest distance between the extra-pseudocapsule lesion and primary tumour (DEP) were evaluated. This
paper will analyse the relationships between these factors.
Results: The positive surgical margin rate was 10% in patients undergoing PN. The study found no significant
relationships between the incidence of satellite foci and tumour diameter, Fuhrman grade, or histological subtype
(all P > 0.05). However, male sex, positive surgical margins, and an incomplete pseudocapsule were associated
with the incidence of satellite foci (P < 0.05). Cases with satellite foci tended to show positive surgical margins.
The DEP was <1.0 mm for all tumours, but there were no significant relationships between the DEP and the tumour
diameter, pathological grade, or histological subtype (P > 0.05).
Conclusion: In T1b RCC, a 1-mm surgical margin would be sufficient to attain integrated resection of the primary
tumour and its cancerous tissue beyond the pseudocapsule. PN was insufficient to prevent a positive surgical mar-
gin, most likely due to the presence of satellite foci.
Keywords: renal cell carcinoma; partial nephrectomy; distance of extra-pseudocapsule lesion; satellite tumours;
safe surgical margin
INTRODUCTION
Presently, for T1a renal cell carcinoma (RCC) (< 4 cm in diameter), partial nephrectomy (PN) is rec-
ommended by the experts' consensus. However, PN is
increasingly being used for resection of T1b RCC tu-
mours (diameter, 4–7 cm). In the 2010 National Com-
prehensive Cancer Network Kidney Cancer guidelines,
PN and radical nephrectomy (RN) were suggested as
standard surgical procedures for T1b RCC,(1) although
the application of PN for T1b RCC remains controver-
sial.
The greatest concern for applying PN is the possibility
of residual tumours. Chen et al.(2) compared T1a and
T1b RCC patients who underwent PN, and found that
the pseudocapsule incompleteness rates and the inci-
dence rates of lesions beyond the pseudocapsule were
significantly higher in patients with T1b RCC, sug-
gesting that PN is not very efficacious for eradication
of T1b RCC. Another concern is that PN is associated
with operative complications, such as renal parenchyma
damage and intrarenal arteries and collecting system
lesion, which can cause urinary leak and bleeding(3)
.PN also carries the postoperative risk of positive sur-
gical margins. Currently, there is no consensus(4–7) on
whether positive surgical margins are a risk factor for
RCC recurrence. Similarly, there is no consensus on the
rational management for patients with positive surgi-
cal margins after PN.(8) Therefore, in order to avoid a
positive surgical margin, it is imperative to excise all
cancerous tissues completely during PN.
As the practice of PN evolved and minimal invasive
techniques were developed to maintain long-term re-
nal function, the traditional surgical margin width was
reduced from 1 cm to 0.5 cm for small local RCC tu-
mours. In 2008, the Chinese Diagnosis and Treatment
of Urological Disease Guide recommended a 0.5–1-cm
surgical margin.(9) As early as 2003, Li et al.(10) proposed
that a 0.5-cm surgical margin was sufficient to eradicate
lesions beyond the pseudocapsule in T1a RCC tumours.
However, other studies have suggested that there were
no relationships between surgical margin width and
RCC progression, recurrence, or survival rates.(11–12)
Therefore, it is likely that a histologically confirmed
tumour-free margin of resection, irrespective of mar-
gin width, is sufficient to achieve complete local ex-
cision of RCC. However, during PN, surgeons attempt
to persist the normal renal parenchyma surrounding the
tumour, which tends to make the surgical margin larg-
er than desirable. To achieve a clear surgical margin,
imaging modalities such as computed tomography and
magnetic resonance imaging are used to locate the tu-
mour and surrounding cancerous tissues. In addition,
ultrasonography is used to locate suspected satellite foci
Urology Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
*Correspondence: Urology Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Tel: +86 13318868013. Fax: +86 020 34070447. E-mail: wenlianxie@126.com.
Received August 2016 & Accepted January 2017
Urological Oncology 2961
during PN,(12) but the risk of a positive surgical margin
also depends on the surgeon’s perioperative predic-
tions of pseudocapsule completeness and normal renal
parenchyma capsule completeness around the tumour,
which could result in widening margin during the sur-
gery.(13) Previous studies on the safe surgical margin for
PN have mostly considered T1a RCC, but this may not
translate well to T1b RCC.(14-15) This retrospective study
aims to evaluate the rational margin for PN of T1b RCC
tumours based on clinicopathological tumour features
such as tumour size, pseudocapsule morphology, tu-
mour histology, and the incidence of satellite foci.
PATIENTS AND METHODS
Study population
In this retrospective study, we analyzed the data from
patients with histological confirmed T1b RCC who un-
derwent PN or RN (all operations were laparoscopic by
two surgeons) at the Sun Yat-sen Memorial Hospital
affiliated with Zhongshan University between October
2008 and December 2014. After reviewing the patients’
medical records, we reviewed the patients’ medical re-
cords and identified 469 patients who met the following
criteria: the presence of a single primary renal tumour;
the absence of metastasis, as determined by preopera-
tive computed tomography (CT) or magnetic resonance
imaging (MRI); and common histological RCC sub-
types such as clear-cell, papillary-cell, and chromo-
phobe-cell carcinomas. Finally, we analyzed the data
from 60 patients, 40 of whom underwent RN and 20 of
whom underwent PN.
Histopathological analysis
In order to determine the maximum tumour diameter,
we fixed the 60 excised tumour tissues in 10% formalin
and cut along the coronal plane of the kidney. For each
tumour specimen, 6 circular specimens from the tumour
surface measuring 1.4 × 1.4 × 0.4 cm3 were collected.
These specimens were obtained from the centre of tu-
mour and consisted of the primary tumour, tumour mar-
gins, and the normal renal parenchyma surrounding the
primary tumour (Figure 1). During the study period,
the surgical margin apart from the tumour in PN was at
least 0.5cm. For the 20 PN-excised tumours, suspected
sites (without surrounding of normal renal parenchyma
by naked eye) at the surgical margin were sampled to
determine the surgical margin status. A total of 398
Table 1: Tumour-associated characteristics
T1b RN PN
Pseudocapsule (n, %)
Complete 25 (41.7) 16 (64.0) 9 (36.0)
Non-infiltrating 6 (10)
Infiltrating 19 (37.1)
Incomplete 35 (58.3) 24 (68.6) 11 (31.4)
No tumour invasion 16 (26.6)
Tumour invasion 13 (21.7)
No pseudocapsule 6 (10)
Margin status (n, %)a
Positive 2 (10)
Negative 18 (90.0)
Satellite foci (n, %)
Positive 17 (28.3) 13 (76.5) 4 (23.5)
Negative 43 (71.7) 27 (62.8) 16 (37.2)
Abbreviations: RN, radical nephrectomy; PN, partial nephrectomy
a Margin status was evaluated in patients who underwent PN alone.
DEP(mm) T1b percentage% Accumulative percentage %
0 16 55.2 55.2
0.01-0.50 7 24.1 79.3
0.51-1.00 6 20.7 100.0
*when pseudocapsule existed and was incomplete
Table 2. Frequency distribution of DEP
Vol 14 No 01 January-February 2017 2962
Safe surgical margin for T1b RCC-Zhang et al.
specimens were paraffin-embedded, sectioned, and
subjected to haematoxylin and eosin staining. Slides
were evaluated using a light microscope with a camera
attachment. All the specimens were examined by one
dedicated pathologist.
Tumour characteristics
Characteristic tumour features are shown in Figure 2. A
complete pseudocapsule was defined as being present
when all tumour samples from the same patient had a
pseudocapsule that continuously separated the tumour
from the normal renal parenchyma. Incomplete pseu-
docapsules was defined where is was found with : no
tumour invasion (Figure 2A), with tumour invasion be-
yond the pseudocapsule (Figure 2B), or as a complete
absence of pseudocapsule (Figure 2C). The distance of
the extra-pseudocapsule lesion (DEP) was defined as
the maximal distance from the outermost margin of the
primary tumour to the outermost layer of the pseudo-
capsule, as measured to a precision of 0.01 mm (Figure
2D). The DEP was defined as 0 mm when incomplete
pseudocapsule had no tumour invasion. The status of
the surgical margin was described as positive if tumour
cells were present, and was described as negative if they
were not. Satellite foci were defined as small distinct
focal points of tumour cells outside the pseudocapsule
and departed from the primary tumour (Figure 2E).(16-
17)
Outcome assessment
SPSS®, version 19.0 (IBM, Armonk, NY, USA) and
Excel® 2010 (Microsoft, Redmond, WA, USA) were
used for all statistical analysis. Differences between
the RN and PN groups were evaluated using Student’s
t-test or the Chi-square test. Differences among factors
possibly affecting DEP were evaluated using the analy-
sis of variance (ANOVA). Relationships between vari-
ables were evaluated using a Pearson’s correlation test.
The two-sided alpha level of 0.05 and a P-value of <
0.05 were considered statistically significant.
All procedures performed in the study involving human
participants were in accordance with the ethical stand-
ards of the institutional and/or national research com-
mittee and with the 1964 Helsinki declaration and its
later amendments or comparable ethical standards.
RESULTS
Histopathological Tumour-associated Characteristics
Safe surgical margin for T1b RCC-Zhang et al.
Table 3: Frequency of DEP according to tumour diameter, Fuhrman grade, and histological subtype
DEP P value
N X ± SD
Tumour diameter (cm)a
4.1–5.0 7 0.61 ± 0.17 -
5.1–6.0 3 0.37 ± 0.24 .015
6.1–7.0 3 0.18 ± 0.11 .006
Fuhrman grade a .070
High differentiation 7 0.58 ± 0.15
Moderate differentiation 4 0.24 ± 0.15
Low differentiation 2 0.43 ± 0.47
Histological type a NA
Clear-cell 13 0.45 ± 0.25
Papillary-cell 0 0
Chromophobe-cell 0 0
Abbreviations: DEP, distance of the extra-pseudocapsule lesion; SD, standard deviation; NA, non-applicable
a Analysis of variance (ANOVA)
Figure 1. Diagrammatic representation of tumour sampling re-
gions
The tumour edge close to the pelvis (A), the tumour edge close to
the renal parenchyma and medulla (C, D, E, and F), and the tumour
edge close to the renal capsule (B).
Urological Oncology 2963
The pseudocapsule morphologies, margin statuses, and
existence of satellite foci are shown in Table 1, both for
the overall patient cohort and groups according to the
surgical procedure. There was no significant difference
in rates of pseudocapsule completeness according to
surgical modality. The majority of patients did not have
satellite foci.In the PN group, the majority of patients
had negative surgical margins.
Factors Affecting the DEP
Distribution of DEP was shown in Table 2. DEP var-
ied significantly as tumour diameter increased. This
appeared to indicate an association between increas-
ing tumour size and decreasing DEP which failed to
achieve statistical significance. In addition, there were
no significant correlations between DEP and patholog-
ical grade. All cases of RCC infiltrating beyond the
pseudocapsule into normal parenchyma were clear-cell
carcinomas (Table 3).
Factors Associated with the Incidence of Satellite Foci
We evaluated the relationship between clinicopatholog-
ical parameters and the incidence of satellite foci (Ta-
ble 4). In 17 cases of positive satellite foci, the distanc-
es between the primary tumour and the satellite focus
ranged from 0.5 mm to 5.2 mm. The presence of satel-
lite foci was not associated with tumour diameter, Fuhr-
man grade, or histological subtype (P > 0.05), but was
associated with sex and pseudocapsule completeness (P
< 0.05). Male patients and patients with an incomplete
pseudocapsule were more likely to have satellite foci.
DISCUSSION
Numerous clinical studies have indicated that PN and
RN have comparable effective local control and dis-
ease-specific survival rates in patients with T1b RCC.
(18–19) The major concern for the application of PN is the
risk of incomplete tumour excision because of tumour
extension beyond the pseudocapsule or the presence of
satellite foci, which are difficult to detect both by using
imaging modalities. In addition, discrepancies concern-
ing the appropriate surgical margin width have been a
cause for concern.(20–21)
The traditional tumour excision margin of 5–10 mm
was applied. However, without a reference point, it
was impossible to excise the thick parenchyma that sur-
rounds the primary tumour evenly, because the bottom
of the margin was usually thinner than the rest of the
margin.(24) In addition, thicker surgical margins are dif-
ficult to achieve by laparoscopic PN within 20–30 min
of hot ischemia, which can lead to an increased risk of
complications.
All DEPs in the present study were well within the
traditional surgical margin width. Based on the DEP,
a 1-mm surgical margin would be sufficient to attain
Table 4: Factors associated with the incidence of satellite foci
Variable Satellite foci P value
Negative Positive
Sex a
Male 29 (64.4) 16 (35.6) .032
Female 14 (93.3) 1 (6.7)
Tumour diameter (cm) a
4.1–5.0 21 (80.8) 5 (19.2) .385
5.1–6.0 14 (63.6) 8 (36.4)
6.1–7.0 8 (66.7) 4 (33.3)
Fuhrman grade a
High differentiation 28 (77.8) 8 (22.2) .433
Moderate differentiation 12 (63.2) 7 (36.8)
Low differentiation 3 (60.0) 2 (40.0)
Margin status a
Negative 16 (88.9) 2 (11.1) .003
Positive 0 (0.0) 2 (100.0)
Histological subtype a
Clear-cell 35 (71.4) 14 (28.6) .988
Papillary-cell 5 (71.4) 2 (28.6)
Chromophobe-cell 3 (75.0) 1 (25.0)
Pseudocapsule a
Complete 22 (88.0) 3 (12.0) .018
Incomplete 21 (60.0) 14 (40.0)
a Chi-square test
Vol 14 No 01 January-February 2017 2964
Safe surgical margin for T1b RCC-Zhang et al.
integrated resection of the primary tumour and its can-
cerous tissue beyond the pseudocapsule. However, this
margin was not sufficient for two patients who did show
positive surgical margins, most likely because those pa-
tients had satellite foci. This suggests that, although PN
with a surgical margin <1 mm might be useful for pre-
venting positive surgical margins by removing residual
tumour, it might not be sufficient for preventing posi-
tive margins caused by satellite foci.
In the present study, the incidence rate of satellite foci
was 28.3%, In this study, the satellite foci incidence
rate was higher than the positive surgical margin rate
of 10.0%. A similar finding was reported in a previous
study of local RCC after PN; the satellite foci incidence
rate was 15.7% and the positive surgical margin rate
was 0.0–7.0%.(11,22) It is likely that some correlation ex-
ists between satellite foci and positive surgical margin.
In 17 cases, the distance between satellite foci and the
primary tumour was 0.5–5.2 mm. However, because
the measured distance was limited by pathological sam-
pling, only those foci in proximity to the tumour could
be observed. This may result in false negative findings.
In 32 cases of multicentric foci, Li et al.(11) found that
23 cases were < 8 mm from the primary tumour, but 9
cases were about 30 mm (range:15–60 mm) . Loran et
al. indicated that the distance between multicentric foci
and the primary tumour was more than 20mm.(25) Taken
together, these results suggest that the traditional surgi-
cal margin width of 5–10 mm would not be sufficient to
remove satellite foci. Local recurrence after PN is more
likely attributable to satellite foci, rather than (in any
substantial sense) residual tumour caused by incom-
plete removal of the primary tumour. Some research-
es show positive surgical margins have been shown to
increase the recurrence risk after PN, but did not affect
the survival of patients. However, others proved pos-
itive surgical margins did not affect local recurrence
or metastases risks after PN.(22) There are a number of
factors that may explain why having a positive surgical
margin did not appear to affect clinical efficacy in these
studies.(23) As mentioned above, because either ectomy
does not completely clear up the satellite foci, it makes
no obvious difference to overall survival no matter
whether the surgical margin is positive or negative.
In general, a narrow surgical margin width is recom-
mended in T1a RCC, but we do not advocate tumour
enucleation for T1b RCC. In the present study, the in-
complete pseudocapsule rate in patients with T1b RCC
was much higher than that reported for T1a RCC.(2) Even
if the pseudocapsule was complete, tumour invasion of
the pseudocapsule was prevalent(76%). Besides, there
is a risk of disrupting the pseudocapsule during tumour
enucleation, which could lead to tumour dissemination.
Both Minervini et al.(26) and Ficarra et al.(21) demonstrat-
ed that cancer cells could be separated from the surgical
margin by a thin layer of chronically inflamed tissues.
However, some sites with incomplete pseudocapsule
did not show an inflammatory layer enveloped (Figure
2B). These results may narrow applications of tumour
enucleation, especially for highly malignant T1b RCC
or tumours with an incomplete pseudocapsule.
There were some limitations in this study: 1) to meet
the inclusion of this study and to match paired groups
demand, it can only recruit 60 patients in all, the num-
ber of patients is relatively small; 2) Although the pres-
ence of satellite foci and their exact location could be
better evaluated in a radical nephrectomy specimen
rather than a partial specimen, more and more patients
choose to use partial nephrectomy. So there is great
significance to explore the relationship between satel-
lite foci and surgical margin in partial nephrectomy; 3)
The follow-up is not long enough to study the long term
prognosis.
CONCLUSIONS
In T1b RCC, a 1-mm surgical margin was sufficient to
excise the primary tumour and its residual tissue be-
yond the pseudocapsule. However, the presence of sat-
Figure 2. Histological tumour features
(A) Incomplete pseudocapsule with no tumour invasion
(B) Incomplete pseudocapsule with tumour invasion
(C) Incomplete pseudocapsule with a complete absence of tumour capsule
(D) The DEP
(E) Satellite foci
PS, pseudocapsule; T, tumour; ST, satellite foci; DEP, distance of the extra-pseudocapsule lesion
Urological Oncology 2965
Safe surgical margin for T1b RCC-Zhang et al.
ellite foci might cause a positive surgical margin. The
incidence of satellite foci was associated with male sex
and an incomplete pseudocapsule in patients who un-
derwent laparoscopic PN. Therefore, we conclude that
laparoscopic PN is not sufficient to remove satellite foci
in patients with T1b RCC.
ACKNOWLEDGEMENT
This study was approved in Department of Urology
Surgery, Sun Yat-sen Memorial Hospital affiliated with
Zhongshan University, as a research project. The au-
thors would like to thank Dr. WenLian Xie and appre-
ciate his support for the preparing of this manuscript.
CONFLICT OF INTEREST
The authors report no conflict on interests.
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