Keywords
CT staging of Wilms’ tumor - diagnostic accuracy of Wilms’ CT - interobserver agreement
Introduction
Wilms’ tumor (WT), the most common pediatric renal tumor, is the model of exemplary
success of multimodality management of cancers with a survival rate of almost 96%.[1] Conventionally surgical-pathological staging is used to decide the management; however,
with the advent of multidetector computed tomography (MDCT), imaging-based prediction
of staging, preoperatively, has become increasingly feasible.[2]
[3] Though there may not be any direct therapeutic implications of predicting the stage,
there is a potential of avoiding difficult surgical exercise if the diagnostic accuracy
of CT staging is good.[4] The existing literature states a poor correlation between radiologic and surgical-pathological
staging, with accuracy reported as low as 38%.[5] These studies are relatively old and may not have explored the potential of multiplanar
reformation that can be obtained on an MDCT.
In our retrospective study, we have evaluated the diagnostic accuracy of MDCT staging
of WT in comparison with surgical-pathological staging (reference standard). We also
performed reliability testing using interobserver agreement in predicting CT stage
through blind review of CT scans by two experienced radiologists.
Materials and Methods
Study Population and Recruitment
This study was approved by the institutional review board (IRB) and was conducted
in a single institution (tertiary cancer care center). This was a retrospective study
design. The inclusion criteria were histopathologic proof of WT, availability of MDCT
images on PACS (Picture Archival and Communication System), and surgery and histopathology
done in the institution. The exclusion criteria were non–Wilms’ renal tumors and bilateral
tumors. Serial 50 WT cases diagnosed between January 2013 and December 2015 and meeting
our eligibility criteria were included in this study.
Study Procedure
Electronic database of CT findings, relevant intraoperative findings, and histopathology
were created. Two radiologists blinded to surgical and histologic findings independently
reviewed the CT scans on workstations, using “live” multiplanar reformation. The radiologists
had 10 and 5 years of experience in radiology (called as observers A and B, respectively).
All the CT scans were performed on a 16-channel MDCT machine, either Lightspeed 16
(General Electric, Milwaukee, Wisconsin, United States) or Somatom emotion (Seimens
Medical Solutions, Pennsylvania, United States). Each child underwent a contrast-enhanced
CT scan after an intravenous injection of 1.5 mL/kg of nonionic iodinated contrast
media.
The extent of involvement in the kidney, size of the mass, renal vein thrombosis,
if present, its extent into the inferior vena cava (IVC), renal sinus involvement,
pelvicalyceal system involvement, ureteric involvement, any evidence or suspicion
of extracapsular spread, and adenopathy were recorded. Each radiologist assigned a
CT stage independently. This information was used for interobserver concordance assessment.
For the final staging, consensus data between two radiologists were also recorded,
and this was compared with surgical-pathological staging (reference standard).
For the patients who had received preoperative chemotherapy, the post-chemotherapy
scans were evaluated and compared with reference standard. For the purpose of this
study, in patients with metastatic disease, only local staging was compared as all
patients underwent surgery as per their treatment protocol. Similarly, if patients
had stage III disease purely by virtue of spillage alone, it was ignored and local
extent was taken into consideration, as this study aims to evaluate the accuracy of
CT scan is assessing the local extent of the disease.
Statistical Analysis
Descriptive statistics of the various morphologic features of WT on imaging were assessed.
Diagnostic accuracy of radiologic staging was assessed in terms of sensitivity, specificity,
positive predictive value (PPV) and negative predictive value (NPV). κ-Coefficient
value was calculated for measuring the degree of agreement between the two observers.
Results
This study population showed an equal distribution between the sexes and an age range
from 1 to 11 years (average age of 4.3 years) ([Table 1]). The tumor was slightly more common on the left side with three patients having
horseshoe kidney. Two patients underwent upfront surgery whereas 48 received four
cycles of chemotherapy. Only one patient (with otherwise stage I disease) had intraoperative
spillage, and this is not considered as stage III disease for the purpose of this
study.
Table 1
Demographics/patients profile
|
Study population
|
50
|
|
Sex distribution
|
Male: 25
|
|
Female: 25
|
|
Age distribution
|
Range: 1–11 y
|
|
Average: 4.3 y
|
|
Laterality
|
Right: 22
|
|
Left: 25
|
|
Horseshoe: 3
|
|
Size (in cc)
|
Smallest: 12 cc
|
|
Largest: 1,800 cc
|
|
Average volume
|
241 cc
|
CT scan correctly staged the disease in 31 (62%) out of 50 patients ([Table 2]). CT scan understaged the disease in 2 (4%) cases, whereas it led to overstaging
in 17 (34%) cases. There was substantial agreement between the two observers in assigning
the stage in 80% of the cases leading to a κ-coefficient of 0.63 ([Table 3]).
Table 2
CT stage versus surgical-pathological stage
|
Reference standard
|
Total
|
|
I
|
II
|
III
|
|
|
Abbreviation: CT, computed tomography.
|
|
CT scan
|
I
|
3
|
1
|
0
|
4
|
|
II
|
4
|
25
|
1
|
30
|
|
III
|
1
|
12
|
3
|
16
|
|
Total
|
8
|
38
|
4
|
50
|
Table 3
Cross-tabulation for CT staging done by two observers
|
Observer B
|
Total
|
|
I
|
II
|
III
|
|
Abbreviation: CT, computed tomography.
|
|
Observer A
|
I
|
4
|
0
|
1
|
5
|
|
II
|
0
|
25
|
4
|
29
|
|
III
|
0
|
5
|
11
|
16
|
|
Total
|
|
4
|
30
|
16
|
50
|
In the final staging ([Table 4]), three out of eight patients with stage I disease had their disease staged correctly.
Four of the stage I patients were assigned stage II by CT, two on the basis of suspected
capsular involvement and one on the basis of suspected sinus involvement. One was
assigned stage III based on radiologically suspicious nodes. Thus, CT accurately staged
only 37.5% of stage I cases while overstaged 62.5%
Table 4
Final staging accuracy of CT scan
|
Stage
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
Abbreviations: CT, computed tomography; NPV, negative predictive value; PPV, positive
predictive value.
|
|
I
|
37.5
|
97.6
|
75
|
89
|
|
II
|
65.7
|
58.3
|
83.3
|
35
|
|
III
|
75
|
71.7
|
18.7
|
97
|
Twenty-five (65.7%) out of 38 patients with stage II disease had their disease staged
correctly. Overstaging occurred in 12 (31.5%) out of 38 patients; 6 were on the basis
of suspected extracapsular spread and 5 for suspected nodal involvement whereas one
case was overstaged on the basis of both being wrongly suspected. Understaging occurred
in 1 (2.6%) out of 38 patients stage II cases due to radiologically occult involvement
of pelvicalyceal system.
Three (75%) out of four patients with stage III disease were identified correctly
based on either peritoneal involvement (n = 1) or adenopathy (n = 3). One (25%) patient with stage III disease was assigned stage II on CT and therefore
under-staged due to radiologically occult retroperitoneal nodal involvement.
Renal capsular involvement ([Fig. 1A, B]) was present in 19 out of 50 pathology specimens. (Even though capsular involvement
was present in 19 specimens, none of the resected specimens showed positive resection
margin as tumor is excised along with perinephric fat and Gerota's fascia.) Observer
A correctly identified renal capsular involvement in 17 cases and ruled it out in
24 cases, giving the sensitivity and specificity of 89% and 77%, respectively ([Table 5]). Observer B was found to be correct in identifying capsular involvement in 15 cases
and ruling out in18 cases, giving sensitivity and specificity of 79% and 58%, respectively
([Table 5]). The PPVs were 54% and 71% for observers A and B, respectively, whereas the NPVs
were 82% and 92%, respectively ([Table 6]). There was moderate strength of agreement between the two observers with κ-value
(K) being 0.44.
Fig. 1 (A) Axial contrast-enhanced CT image shows tumor arising from the upper pole infiltrating
into perirenal soft tissue with extracapsular extension. (B) Axial contrast-enhanced CT image shows tumor arising from right kidney extending
into the anterior and posterior perinephric fat (black arrow).
Table 5
Extent of disease: sensitivity and specificity for observers A and B
|
Parameters
|
Observer A
|
Observer B
|
κ
|
|
Sensitivity (%)
|
Specificity (%)
|
Sensitivity (%)
|
Specificity (%)
|
|
Abbreviation: PCS, pelvicalyceal system.
|
|
PCS involvement
|
76
|
42
|
82
|
58
|
0.50
|
|
Ureteric spread
|
50
|
91
|
33
|
95
|
0.69
|
|
Adenopathy
|
25
|
83
|
75
|
83
|
0.50
|
|
Capsular invasion
|
79
|
58
|
89
|
77
|
0.44
|
|
Sinus involvement
|
64
|
57
|
79
|
62
|
0.67
|
|
Renal vein thrombus
|
100
|
100
|
100
|
100
|
1.0
|
Table 6
Extent of disease: PPV and NPV for observers A and B
|
Parameters
|
Observer A
|
Observer B
|
|
PPV (%)
|
NPV (%)
|
PPV (%)
|
NPV (%)
|
|
Abbreviations: NPV, negative predictive value; PCS, pelvicalyceal system; PPV, positive
predictive value.
|
|
PCS involvement
|
42
|
82
|
48
|
82
|
|
Ureteric spread
|
43
|
91
|
50
|
93
|
|
Adenopathy
|
11
|
93
|
27
|
97
|
|
Capsular invasion
|
54
|
82
|
71
|
92
|
|
Sinus involvement
|
67
|
52
|
62
|
74
|
|
Renal vein thrombosis
|
100
|
100
|
100
|
100
|
Renal vein involvement ([Fig. 2A, B]) was identified in 7 (14%) out of 50 cases. Sensitivity, specificity, PPV, and NPV
of CT scan were 100% for both the observers in detection of renal vein thrombosis
([Tables 5]
[6]). One patient had thrombosis limited to the main renal vein, two patients showed
thrombi extending into the infrahepatic IVC, and three patients had thrombi extending
into the retrohepatic IVC. In one patient, the tumor thrombus was stopping short of
the atrium. All these extensions were correctly detected on CT.
Fig. 2 (A) Axial contrast-enhanced CT image shows tumor extending into the left renal vein (black
arrow). (B) Coronal reformatted image shows tumor extending into the intrahepatic segment of
inferior vena cava.
Renal sinus involvement ([Fig. 3B]) was present in 29 (58%) out of 50 specimens. The sensitivity and specificity for
observer A were 64% and 57%, respectively, and for observer B these were 79 and 62%,
respectively ([Table 5]). Good interobserver agreement was observed in assessment of renal sinus invasion
on CT scan with K = 0.63. Renal pelvicalyceal system (PCS) involvement ([Fig. 3A, B]) was identified in 17 (34%) out of 50. The sensitivity was high (76% and 82% for
observers A and B, respectively), but specificity was low for both the observers (42%
and 58%, respectively).
Fig. 3 (A) Three minutes delayed oblique axial CT image shows opacified pelvicalyceal system
with the tumor bulging and displacing the left renal calyces; however, no definite
invasion is observed. (B) Axial contrast-enhanced CT shows invasion of pelvicalyceal system and renal sinus.
Ureteric involvement was present in 6 (12%) out of 50 specimens. Both the observers
showed high specificity but poor sensitivity in predicting ureteric involvement ([Tables 5]
[6]). The Interobserver agreement was very good with K = 0.6. The NPV for ureteric involvement
was 91 to 93%. Renal hilar and retroperitoneal adenopathy ([Fig. 4A, B]) was observed in 4 (8%) out of 50 cases, and the correlation was poor between the
two observers. However, the NPV was high—93% for observer A and 97% for observer B.
Fig. 4 (A) Axial contrast-enhanced CT image shows large tumor occupying the right kidney with
preaortic lymph node (asterisk). (B) Post-chemotherapy axial CT image shows complete regression in the lymph node and
significant reduction in tumor size.
Discussion
The overall diagnostic accuracy of CT scan in staging of WT was found to be 62% in
our study. However, as the disease stage increased, the diagnostic accuracy showed
improvement: it was 37.5% in stage I disease, 66% in stage II, and 75% in stage III
([Table 4]).
A retrospective study by Gow et al concluded that CT scan appears to have poor correlation
with histologic staging.[5] In their study, out of 26 WT cases, CT scan correctly staged only 10 (38%) cases.
None of the patients with stage I disease had their disease staged correctly. They
were overstaged as II and III; 66% of cases with stage II disease and 60% of stage
III were staged correctly. They found that CT has difficulty for discriminating between
stages I and II disease and also stages II and III disease. They also found a consistent
difficulty in determining capsular involvement or nodal involvement.
Another prospective study performed by Abdelmaboud et al on 32 WT children concluded
that MDCT represents a reliable diagnostic method for evaluating WT. It is accurate
and sensitive in diagnosing stages I, IV, and V but is not as accurate in the diagnosis
of stages II and III and has poor correlation with histopathologic data.[6]
A retrospective review of 179 cases by Abdelhalim et al concluded that the validity
of CT staging of childhood renal tumors remains doubtful.[7] The authors of this publication find that the CT is more accurate for tumors without
extracapsular extension. In their study, CT overstaged 21.4%, 65.2%, and 46.5% of
tumors in the upfront surgery, pre-chemotherapy, and post-chemotherapy scans, respectively,
and understaged 10.7%, 3%, and 4.7%, respectively.
Thus, the previously published data revealed a poor correlation between radiologic
and pathologic staging.
In our study, the accuracy of CT staging is better than what has previously been reported
and could be attributed to MDCT. Robust CT staging is not required to replace the
well-established surgical-pathological staging systems that form an integral part
of treatment protocols used across the globe. Currently, stage III disease requires
a multimodal treatment: chemotherapy, surgery, and radiotherapy, whereas stage II
disease is treated with chemotherapy and surgery alone.[8] Moreover, chemotherapy for stages I and II comprises two drugs—vincristine and dactinomycin—whereas
that for stage III also includes doxorubicin in addition to these two drugs.[8]
Thus, if we could use CT scan to identify extrarenal disease like infiltration of
adjacent organs, adenopathy, ureteric involvement, peritoneal disease, and tumor thrombus
that could potentially be stage III disease, we could avoid upfront surgery. Our study
shows 97% NPV for stage III disease, which means that if CT scan does not identify
extrarenal disease, it is unlikely to be present. Identification of such disease status
may not be relevant where “state of the art” cancer centers are available as the pediatric
oncology team is likely to have experts in surgery, radiotherapy, and chemotherapy
to offer the multimodal treatment.[4] However, in resource-constrained countries or areas where radiotherapy may not be
available, an accurate CT staging can help in triaging patients at the right time.
For example, patients with probable stages I and II disease may undergo surgery followed
by chemotherapy while caution would be advocated in suspected stage III disease and
patients may be preferably referred to a tertiary cancer center at the right time.
This may help in achieving better outcomes at smaller centers and reduce the burden
on tertiary centers. In effect, CT scan staging will contribute in appropriate resource
allocation.
In our study, when we did subset analysis such as predicting tumor thrombus into the
IVC or retroperitoneal adenopathy, imaging was found to be useful ([Table 7]). For example, CT scan demonstrated the presence and even the extent of tumor thrombus
in the renal vein or IVC with 100% accuracy. Prior knowledge of extent of thrombus
helps in better planning the surgery. Imaging is also useful for ruling out disease
in extracapsular structures; for example, in our study, NPV for ureteric involvement
was 91 to 93% and that for retroperitoneal adenopathy was 93 to 97%. In another retrospective
review of 26 CT scans by Silva et al,[9] CT tumor showed low specificity and low PPV in the detection of lymph node dissemination;
however, the reported NPV was 100%.
Table 7
Overall validity of CT scan (after concordance between two radiologists)
|
Parameters
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
Abbreviations: CT, computed tomography; NPV, negative predictive value; PCS, pelvicalyceal
system; PPV, positive predictive value.
|
|
PCS involvement
|
79
|
50
|
45
|
82
|
|
Ureteric spread
|
41.5
|
93
|
46.5
|
92
|
|
Adenopathy
|
50
|
83
|
19
|
95
|
|
Capsular invasion
|
84
|
67.5
|
62.5
|
87
|
|
Sinus involvement
|
71.5
|
59.5
|
70.5
|
60
|
|
Renal vein thrombosis
|
100
|
100
|
100
|
100
|
Evaluation of the renal sinus and PCS is poor probably because of large size of these
tumors. Both these can get compressed, and this is can lead to overestimation of invasion.
However, this is of doubtful clinical consequence as partial nephrectomy is rarely
offered to unilateral WT.[8]
Evaluation of renal capsule is again difficult in the presence of large tumors, especially
in children in whom the perinephric fat is also limited. The interobserver agreement
was also only little better than fair in assessment, reiterating the difficulty. However,
CT scan helps in ruling out invasion with NPV of 82 to 92% in our study.
Other studies have found similar difficulties in assessment of the capsule and lymph
nodes with malignant abdominal tumors in general and with WT specifically. Damgaard-Pedersen
et al suggest that capsular determination in children is difficult because of the
sparse amount of perivisceral fat in tissue plane and nodal evaluation is difficult
because of the paucity of fat in retroperitoneal tissue planes.[10]
Our study had certain limitation, with the most significant being that it was a retrospective
study. It also did not have equal distribution of cases across the stages, with most
cases being stage II. The lower incidence of stage I disease could be because we are
a tertiary cancer center and hence more likely to treat advanced cases. The incidence
of stage III is also low as we routinely administer preoperative chemotherapy to most
of our patients.
Conclusions
CT is a valuable diagnostic tool for evaluating WT. The diagnostic accuracy of CT
scan for predicting the likely stage improves with advanced stage of the disease,
where surgery is more exigent. CT is extremely valuable in assessment of tumor thrombus
and in ruling out invasion of adjacent organs and nodal disease. Therefore, imaging
has the potential to optimize the therapeutic approach and may thus help in improving
outcomes, especially in the resource-limited countries.
The treatment strategy should be based on the well-established surgical and pathologic
staging systems to avoid the hazards of inaccurate staging.
