Keywords
child - kidney neoplasm - clear cell sarcoma - renal cell carcinoma
Introduction
Pediatric renal tumors constitute 3.2 to 11.1% of all cancers among children globally.[1] Among these, Wilms tumor is the most prevalent pediatric renal tumor.[2] It has been the primary focus of various collaborative groups, including the Children's
Oncology Group (COG) in North America, the International Society of Pediatric Oncology
(SIOP), and the UKCCSG (United Kingdom Children's Cancer Study Group) in Europe. Their
collaborative research efforts have played a pivotal role in advancing the understanding
and management of Wilms tumor.[3] As a result, the overall 3- to 5-year survival rates of Wilms tumor have now surpassed
90% in high-income countries.[4]
Non-Wilms renal tumors (NWRTs) constitute a small but clinically important subgroup
of pediatric renal tumors, comprising only 10 to 20% of all pediatric renal tumors.[5]
[6]
[7]
[8]
[9] This diverse group encompasses diagnoses such as clear cell sarcoma of the kidney
(CCSK), renal cell carcinoma (RCC), malignant rhabdoid tumor of the kidney (MRTK),
congenital mesoblastic nephroma (CMN), and other rare entities such as primitive neuroectodermal
tumors (PNETs) and soft tissue sarcomas. They pose significant diagnostic and therapeutic
challenges, often mimicking Wilms tumor in both clinical and radiological evaluations.
Accurate histological diagnosis is therefore crucial, as treatment strategies differ
substantially from those employed for Wilms tumor. Individualized management approaches
are essential to improve outcomes in this unique group of tumors.[10]
[11]
[12]
Despite their clinical importance, NWRTs are less well studied due to their heterogeneity
and rarity. Notably, there are only sparse published data from India on the outcomes
of children with NWRTs. This study aims to document our experience of managing the
children with NWRTs in our center.
Materials and Methods
Study Design, Setting, and Participants
We retrospectively analyzed the children evaluated for renal tumors between January
2000 and December 2023 at the pediatric oncology unit of our institute, which is a
tertiary care cancer center in Southern India.
Inclusion and Exclusion Criteria
This study included patients aged less than 18 years with a confirmed histopathological
diagnosis of NWRTs, including, but not limited to, CCSK, RCC, MRTK, CMN, and other
rare renal tumors like PNETs, soft tissue sarcoma, etc.
Objectives
The primary objective of this study was to describe the demographic profile, clinical
presentation, and treatment modalities employed in the management of children with
NWRTs at our unit. The secondary objective was to evaluate and report their survival
outcomes.
Expected Outcomes
The primary outcome was the distribution of demographic characteristics, clinical
features at presentation, and treatment modalities employed among study participants.
The secondary outcome was survival, assessed in terms of event-free survival (EFS)
and overall survival (OS).
Data Collection
Data regarding the clinical features, such as age, gender, presenting symptoms, duration
of symptoms, and sites of involvement, were extracted from medical records. We also
collected the reports of hematological, biochemical investigations, imaging studies
(ultrasound scan, computerized tomography [CT] scan, 18F-fluoro-de-oxy glucose-positron emission tomography [18F-FDG-PET]-CT scan, magnetic resonance imaging [MRI] studies, and bone scintigraphy),
and histopathological studies from the medical records. Histopathological reports
were reviewed to confirm tumor type and assess relevant pathological features. Treatment
details, including chemotherapeutic regimens, surgical interventions, and radiotherapy,
were obtained by a thorough review of patient records. All patients in the study were
tracked by medical record review until October 2024.
Initial Evaluation and Treatment
All patients presenting with a renal mass underwent contrast-enhanced CT of the abdomen
and pelvis to characterize the primary tumor and assess its extent. The clinical features
and imaging characteristics were utilized to formulate a presumptive pretreatment
diagnosis of Wilms tumor versus NWRT. The treatment decisions of the study subjects
were taken after discussion in multidisciplinary tumor board. We followed a hybrid
approach for the management of children with renal tumors: upfront nephrectomy was
performed in select subset of patients deemed operable, while others received preoperative
chemotherapy followed by delayed nephrectomy. Pretherapy tissue biopsy was performed
selectively in patients with atypical clinical or radiological features, where the
presumptive diagnosis was uncertain. Not all patients receiving preoperative chemotherapy
underwent tissue biopsy. Staging investigations, including chest X-ray, CT chest,
MRI brain, 18F-FDG PET-CT, and bone scintigraphy, were performed as indicated based on the presumptive
and/or final histopathological diagnosis. The resources for treatment of pediatric
renal tumors and the treatment protocol have evolved in the author's unit during the
study period and therefore the treatment of the patients enrolled in the study is
heterogeneous.
Data Management and Statistical Considerations
A standardized case record form was created to systematically capture the data relevant
to the study. The data was entered in Microsoft Excel 2016 (Microsoft, Redmond, California,
United States). Data analysis was performed with STATA/SE 11.2 (Stata Corp, College
Station, Texas, United States). To facilitate meaningful interpretation of outcomes
across this heterogeneous group of tumors, we classified the NWRTs into three groups
based on their therapeutic requirements as follows ([Fig. 1]):
Fig. 1 Distribution of children with renal tumor treated in our unit between January 2000
and December 2023.
Group I: Benign tumors requiring surgery only, including mesoblastic nephroma, cystic
nephroma, and cystic partially differentiated nephroblastoma
Group II: Malignant tumors requiring surgery only, including RCC
Group III: Malignant tumors requiring surgery, chemotherapy more intensive than the
Wilms tumor regimen with or without radiotherapy, including CCSK, MRTK, PNET, soft
tissue sarcomas, etc.
Therapeutic misclassification was defined as the erroneous labeling or treatment of
one histological subtype as another, potentially leading to inappropriate therapy.
An event was defined as treatment abandonment or death due to any cause or relapse,
or progression of the disease. EFS was defined as the time from the date of diagnosis
to the date of the first documented event. OS was defined as the time from the date
of diagnosis to death from any cause. Patients without an event or death were censored
at the date of last follow-up. The Kaplan–Meier method was used to estimate EFS and
OS, along with the corresponding 95% confidence intervals (CIs).
Ethical Approval
Prior approval and clearance were obtained from the institutional ethics committee
(Ref No: IEC/2025/April 25). All procedures performed in studies involving human participants
were in accordance with the ethical standards of the institutional and/or national
research committee andwith the 1964 Helsinki Declaration and its later amendments
or comparable ethical standards.
Results
During the study period of 24 years (January 2000 to December 2023), a total of 89
children were evaluated for renal tumor in our center. Out of which, 72 children (81%)
were diagnosed with Wilms tumor. This article presents the outcome of 17 children
(19%) managed as NWRTs in our center during the study period. Among the 17 patients,
16 children were diagnosed and managed upfront in our center, while 1 child was referred
to us following disease relapse after initial treatment elsewhere ([Fig. 1]). The median age at diagnosis of the study population was 47 months (range: 2–210
months). There was a striking male predominance (M: F ratio 3:1) within the study
cohort. Of the 17 patients, 11 had right-sided involvement, while 6 had tumors on
the left side. A rising trend in the number of children diagnosed with NWRTs was noted
over time, with two patients (12%) diagnosed between 2000 and 2007, seven patients
(41%) between 2008 and 2015, and eight patients (47%) between 2016 and 2023.
The distribution of histological variants within our study cohort was as follows:
CCSK (n = 6; 35%), RCC (n = 4; 24%), PNET (n = 2; 12%), non-rhabdomyomatous soft tissue sarcoma (n = 2; 12%), mesoblastic nephroma (n = 2; 12%), and multicystic nephroma (n = 1; 5%). Based on the aforementioned classification criteria, 3 children were categorized
into group I, 4 into group II, and 10 into group III ([Fig. 1]).
Baseline Characteristics
The baseline characteristics of the study population are summarized in [Table 1]. Patients in group II had a higher median age at presentation (141 months) than
those in groups I (21 months) and III (36.5 months). All the patients in group I (100%)
presented with abdominal mass/distension without any abdominal pain or hematuria.
Abdominal pain and hematuria were more frequent in group II, affecting 75 and 50%
of patients, respectively, compared to 30 and 20% in group III. Hypertension was observed
in four patients, distributed as follows: one patient in group I, one in group II,
and two in group III. Larger tumors were observed in group I (median tumor volume:
609.65 cm3) compared to group II (median tumor volume: 165.2 cm3) and group III (median tumor volume: 372.7 cm3). Calcifications and lymphadenopathy were most frequently documented in group III
(38 and 50%, respectively). Intravascular thrombus was seen in one patient in group
II and two patients in group III. Distant metastases were identified in two patients,
both belonging to group III.
Table 1
Baseline characteristics of children with non-Wilms renal tumor treated in our unit
between January 2000 and December 2023
|
Characteristics
|
Overall
(n = 17)
|
Group 1
(n = 3)
|
Group 2
(n = 4)
|
Group 3
(n = 10)
|
|
Age
Median (range)
(mo)
|
47 (2–210)
|
21 (2–69)
|
141 (47–199)
|
36.5 (13–210)
|
|
Gender, n (%)
Male
Female
|
13 (76%)
4 (24%)
|
2 (67%)
1 (33%)
|
4 (100%)
-
|
7 (70%)
3 (30%)
|
|
Year of diagnosis
2000–2007
2008–2015
2016–2023
|
2 (12%)
7 (41%)
8 (47%)
|
1 (33%)
2 (67%)
-
|
1 (25%)
2 (50%)
1 (25%)
|
-
3 (30%)
7 (70%)
|
|
Presenting symptoms, n (%)
|
|
|
|
|
|
Abdominal mass/distension
|
12 (70%)
|
3 (100%)
|
–
|
9 (90%)
|
|
Abdominal pain
|
6 (35%)
|
–
|
3 (75%)
|
3 (30%)
|
|
Hematuria
|
4 (23%)
|
–
|
2 (50%)
|
2 (20%)
|
|
Hypertension, n (%)
|
|
|
|
|
|
Present
Absent
Not known
|
4 (23%)
9 (53%)
4 (24%)
|
1 (33%)
1 (33%)
1 (34%)
|
1 (25%)
3 (75%)
-
|
2 (20%)
5 (50%)
3 (30%)
|
|
Laterality, n (%)
|
|
|
|
|
|
Right
Left
|
11 (65%)
6 (35%)
|
2 (67%)
1 (33%)
|
4 (100%)
-
|
5 (50%)
5 (50%)
|
|
Imaging characteristics
|
|
|
|
|
|
Tumor volume (cm3), median (range)[a]
[c]
|
255.65 (5.9–1573.11)
|
609.65 (219.3–1000)
|
165.2 (5.9–203.4)
|
372.7 (24–1573.11)
|
|
Calcification, n (%)[b]
|
4 (27%)
|
–
|
1 (25%)
|
3 (38%)
|
|
Intravascular thrombus, n (%)[b]
|
3 (20%)
|
–
|
1 (25%)
|
2 (25%)
|
|
Lymphadenopathy, n (%)[b]
|
5 (33%)
|
–
|
1 (25%)
|
4 (50%)
|
|
Metastasis, n (%)
|
2 (12%)
|
–
|
–
|
2 (20%)
|
Note: Group I: Benign tumors requiring surgery only (including mesoblastic nephroma,
cystic nephroma, cystic partially differentiated nephroblastoma). Group II: Malignant
tumors requiring surgery only (including renal cell carcinoma). Group III: Malignant
tumors requiring surgery, chemotherapy (more intensive than the Wilms tumor regimen)
with or without radiotherapy (including clear cell sarcoma of kidney, malignant rhabdoid
tumor of kidney, primitive neuroectodermal tumors, soft tissue sarcomas, etc.).
a Tumor volume data missing in 3 children.
b Data missing in 2 children.
c Tumor volume = Length (cm) × Width (cm) × Thickness (cm) × 0.5.
Management
The management details of our study population are depicted in [Table 2]. Among the study cohort, 11 children (65%) underwent upfront nephrectomy, while
the remaining 6 children (35%) received preoperative chemotherapy, followed by delayed
nephrectomy.
Table 2
Treatment details of children with non-Wilms renal tumor treated in our unit between
January 2000 and December 2023
|
Patient no.
|
Age (mo)
|
Gender
|
Diagnosis
|
Pretreatment biopsy
|
Preop chemotherapy
|
Surgery
|
Postop chemotherapy
|
Postop radiotherapy
|
Therapeutic misclassification
|
|
Group I: Benign tumors requiring surgery only
|
|
1
|
69
|
M
|
Mesoblastic nephroma
|
Not done
|
VA × 4 weeks
|
Delayed nephrectomy
|
No
|
No
|
Yes
|
|
2
|
2
|
M
|
Mesoblastic nephroma
|
Not done
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
3
|
21
|
F
|
Multicystic nephroma
|
Not done
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
Group II: Malignant tumors requiring surgery only
|
|
4
|
126
|
M
|
Renal cell carcinoma
|
Not done
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
5
|
156
|
M
|
Renal cell carcinoma
|
Renal cell carcinoma
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
6
|
199
|
M
|
Renal cell carcinoma
|
Renal cell carcinoma
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
7
|
47
|
M
|
Renal cell carcinoma
|
Not done
|
No
|
Upfront nephrectomy
|
No
|
No
|
No
|
|
Group III: Malignant tumors requiring surgery, chemotherapy (more intensive than WT
regimen) ± radiotherapy
|
|
8
|
19
|
M
|
Clear cell sarcoma of Kidney
|
Not done
|
No
|
Upfront nephrectomy
|
EE4A regimen × 19 weeks
|
Yes (24 Gy)
|
Yes
|
|
9
|
13
|
M
|
Clear cell sarcoma of kidney
|
Not done
|
No
|
Upfront nephrectomy
|
Regimen I × 24 weeks
|
Yes
|
No
|
|
10
|
47
|
F
|
Synovial sarcoma
|
Not done
|
VA × 4 weeks
|
Delayed nephrectomy
|
IA × 1 cycle
|
No
|
Yes
|
|
11
|
80
|
F
|
Clear cell sarcoma of kidney
|
Wilms tumor
|
VA × 4 weeks
|
Delayed nephrectomy
|
SIOP RTSG 2016 regimen (CCSK) × 34 weeks
|
Yes (10.8 Gy)
|
Yes
|
|
12
|
158
|
M
|
Spindle cell sarcoma
|
Spindle cell sarcoma
|
IA × 3 cycles
|
Not done
|
No
|
No
|
No
|
|
13
|
20
|
M
|
Clear cell sarcoma of kidney
|
Not done
|
No
|
Upfront nephrectomy
|
Regimen I × 24 weeks
|
Yes (10.8 Gy)
|
No
|
|
14
|
18
|
M
|
Clear cell sarcoma of kidney
|
Not done
|
No
|
Upfront nephrectomy
|
SIOP RTSG 2016 regimen (CCSK) × 1 week
|
No
|
No
|
|
15
|
210
|
M
|
Ewing sarcoma
|
Not done
|
No
|
Upfront nephrectomy
|
Non-Dose-dense VDC/IE × 16 cycles
|
Yes (45 Gy)
|
No
|
|
16
|
26
|
M
|
Clear cell sarcoma of kidney
|
Synovial sarcoma
|
VA × 2 weeks
|
Delayed nephrectomy
|
Regimen I × 24 weeks
|
Yes (10.8 Gy)
|
Yes
|
|
17
|
180
|
F
|
Ewing sarcoma
|
Ewing's sarcoma
|
VDC × 1 cycle
|
Not done
|
No
|
No
|
No
|
Abbreviations: EE4A regimen, vincristine + actinomycin D; F, female; IA, ifosfamide + adriamycin;
IE, ifosfamide + etoposide; M, male; Regimen I, vincristine + doxorubicin + cyclophosphamide + etoposide;
SIOP RTSG 2016 (CCSK) regimen, ifosfamide + cyclophosphamide + carboplatin + etoposide + doxorubicin;
VA, vincristine + actinomycin D; VDC, vincristine + doxorubicin + cyclophosphamide.
Upfront nephrectomy: Of the 11 children who underwent upfront nephrectomy, 2 were classified under group
I, 4 under group II, and 5 under group III. Pretreatment biopsy was performed in two
of these children, both from group II, with findings concordant with the final subsequent
histopathological diagnosis following nephrectomy.
Delayed nephrectomy: Of six children who received preoperative chemotherapy followed by delayed nephrectomy,
one child was classified under group I while the remaining five under group III. Among
the six children who received preoperative chemotherapy, the regimens administered
were vincristine and actinomycin D (VA) in four patients, ifosfamide and doxorubicin
(IA) in one patient, and vincristine, doxorubicin, and cyclophosphamide (VDC) in one
patient. According to the SIOP Renal Tumor Study Group (SIOP RTSG) 2016 recommendations
for biopsy, a pretherapy biopsy was indicated in five of these children. However,
biopsy was performed in only three of these patients, whereas one patient underwent
biopsy despite being not indicated as per the criteria. Among the four children who
underwent pretherapy biopsy before preoperative chemotherapy, two had discordant histological
diagnosis compared to the subsequent postnephrectomy histological diagnosis, while
the other two did not undergo nephrectomy due to disease progression before surgery.
Therapeutic Misclassification
Notably, one of the seven patients in groups I and II (which typically do not require
preoperative chemotherapy) received preoperative chemotherapy. None of the patients
in groups I or II received adjuvant chemotherapy or radiotherapy, aligning with standard
treatment protocols for these groups. However, the children in group III received
adjuvant chemotherapy (n = 8; 80%) and radiotherapy (n = 6; 60%) as dictated by their final histology and stage, as summarized in [Table 2].
Five children in our study cohort (29%) experienced therapeutic misclassification—one
from group I and four from group III. Only one child (9%) among 11 patients who underwent
upfront nephrectomy suffered therapeutic misclassification. Four out of six children
(66%) who received preoperative chemotherapy also experienced therapeutic misclassification.
Of these four children, two underwent biopsy with discordant results; two children's
biopsy was indicated as per the SIOP RTSG 2016 biopsy criteria, but not performed.
Survival
The median follow-up duration of the study population who remained alive without any
evidence of disease was 97.5 months (range: 25–136 months). The 5-year EFS and OS
rates of the entire study cohort were 59% (95% CI: 32–78%) and 62% (95% CI: 34–81%),
respectively. The Kaplan–Meier survival curves depicting EFS and OS across the three
groups are shown in [Fig. 2A] and [B]. Group I demonstrated excellent outcomes, with both 5-year EFS and OS rates at 100%.
The 5-year EFS and OS rates were both 75% (95% CI: 13–96%) among the patients belonging
to group II. The 5-year EFS and OS rates of group III patients were 40% (95% CI: 12–67%)
and 43% (95% CI: 12–71%), respectively.
Fig. 2 (A) Event-free survival of children with non-Wilms renal tumor treated in our unit between
January 2000 and December 2023 (N = 17). (B) Overall survival of children with non-Wilms renal tumor treated in our unit between
January 2000 and December 2023 (N = 17).
Discussion
This study shares our experience and outcomes of treating children with NWRTs at a
tertiary cancer care center in an low-middle income country (LMIC). NWRTs accounted
for 19% of all pediatric renal tumors treated in our unit over a 24-year period, reflecting
their relative rarity. They also demonstrated variable clinical presentations and
outcomes, reiterating the need for individualized therapeutic approaches for this
group of tumors.
The incidence rate of NWRTs in our study population (19%) is consistent with previously
reported rates, ranging from 13.6 to 20.2%.[5]
[6]
[7]
[8]
[9] CCSK was the most common histological variant reported among our study subjects,
followed by RCC. This finding aligns with the reports of Qureshi et al from Mumbai
and Saula and Hadley from South Africa, who also identified CCSK as the most common
histological variant among NWRTs.[5]
[8] In contrast, studies by Zhuge et al, Fang et al, and Doganis et al reported RCC,
MRTK, and CMN as the predominant histological subtypes in their respective cohorts.[6]
[9]
[13] Such differences in the distribution of NWRTs may be partly attributed to variations
in referral patterns, reporting practices, and regional disease prevalence.
Differentiating NWRTs from the more common Wilms tumor is the crucial step in the
management of a child with renal tumors.[10] Age at presentation, along with clinical features, and imaging characteristics,
often aids in formulating a presumptive diagnosis in children presenting with a renal
mass. Early and accurate presumptive identification of NWRTs based on atypical clinical
and imaging features is essential for guiding an appropriate therapeutic approach,
which differs from that for Wilms tumor.[14] The rising trend in the number of children diagnosed with NWRTs over the years likely
reflects greater awareness and improved diagnostics. Yet, therapeutic misclassification
persisted (five cases; two in 2008–2015, three in 2016–2023), highlighting continued
diagnostic challenges.
Although NWRTs can occur in children of all age groups, the peak age for different
tumor types is distinct. The higher median age at presentation among the group II
study cohort likely explains the absence of therapeutic misclassification in this
group. Whereas the median age at diagnosis for group I and group III patients overlaps
with the typical age of presentation of Wilms tumor, which poses a diagnostic challenge.[14]
[15] There is a striking male predominance among our study population with NWRTs compared
to those with Wilms tumor. Notably, abdominal pain and hematuria were characteristically
absent in patients with benign variants of NWRTs (group I). In contrast, these symptoms
were more common among patients with malignant variants (group II and group III),
reflecting their more aggressive clinical behavior.
Along with age at presentation, tumor volume has emerged as another reliable parameter
for differentiating NWRTs from Wilms tumor. Studies by de la Monneraye et al and Welter
et al reported that RCC is usually smaller at presentation. Consistent with these
findings, our patients belonging to group II presented with a lower median tumor volume
than those in group I and group III.[14]
[15]
[16] A biopsy is usually recommended whenever the clinical and imaging findings suggest
an increased probability of NWRTs. Out of six pretherapy tissue biopsies performed
among study cohort, four biopsy results led to changes in clinical management. However,
therapeutic misclassification occurred in two children despite undergoing pretreatment
biopsy, underscoring the challenges in obtaining an accurate histological diagnosis
from small tissue samples.
Consistent with the majority (54%) of previously published reports from India, we
also adopted a hybrid approach for the management of children with renal tumors: upfront
nephrectomy for a select subset of patients and preoperative chemotherapy followed
by delayed nephrectomy for others.[17] Among the patients with NWRTs in our study cohort, the majority (65%) underwent
upfront nephrectomy, while the remaining (35%) received preoperative chemotherapy.
In contrast, the Wilms tumor cohort from our unit demonstrated a reverse trend, with
28% undergoing upfront nephrectomy and 72% receiving preoperative chemotherapy followed
by delayed nephrectomy.[18] Such differential distribution of Wilms tumor and NWRTs between upfront and delayed
nephrectomy has also been reported by Qureshi et al.[5]
[19] This approach of preoperative chemotherapy followed by delayed nephrectomy is well-suited
to Wilms tumor, but it carries an inherent substantial risk of therapeutic misclassification
in the context of NWRTs.[20] This was clearly evident in our study population, where therapeutic misclassification
occurred more frequently among patients receiving preoperative chemotherapy compared
to those undergoing upfront nephrectomy (66% vs. 9%).
The benign variants of NWRTs are potentially curable with nephrectomy alone, as evidenced
by children belonging to group I of our study cohort, all of whom remained disease-free
beyond 5 years following nephrectomy. Similarly, children with RCC in group II demonstrated
a 5-year survival rate of 75% with nephrectomy alone. These outcomes align with previously
reported survival rates ranging from 60 to 85%.[21]
[22] In contrast, the outcomes of children classified in group III in our study, comprising
a heterogeneous cluster of histological diagnoses, were poorer compared to the other
groups. This group warranted a more individualized approach to management, including
a more intensive chemotherapy regimen and, in some cases, radiotherapy. This was further
complicated by a higher incidence of therapeutic misclassification in group III. Four
out of five patients who suffered therapeutic misclassification in our study belonged
to group III, which underscores the complexity and diagnostic ambiguity associated
with these tumor types. The survival outcomes of our cohort were comparable to those
reported by Qureshi et al, which represents the largest published cohort of NWRTs
from India.[5]
NWRTs represent a heterogeneous group of clinically important childhood renal malignancies.
Their relative rarity and diagnostic difficulties compared to Wilms tumor have hindered
the progress in understanding their molecular biology and developing evidence-based
therapeutic strategies to improve survival outcomes. Collaborative efforts between
national and international centers to strengthen childhood renal tumor registries
and biobanking studies could play a pivotal role in bridging the knowledge gap pertaining
to these rare malignancies.[10]
[11] For instance, the COG AREN03B2 study prospectively collected biological tissues,
histologic data, radiographic imaging, therapeutic strategies, and outcomes for all
children with renal tumors, including both Wilms tumors and NWRTs.[23] Similarly, the SIOP RTSG 2016 study integrated research and therapeutic recommendations
for both Wilms tumor and NWRTs into a unified framework under the UMBRELLA protocol.[24] Sadly, outside of North America and Europe, such renal tumor-specific multicentric
registry studies are rare. Our findings suggest upfront nephrectomy approach and pretherapy
biopsy reduce the risk of therapeutic misclassification, but do not eliminate it completely.
However, this needs to be validated in a large multicenter study before being adopted
into clinical practice.
This study reports the real-world experience of managing children with NWRTs in a
tertiary care center in Southern India, highlighting the diagnostic and therapeutic
challenges encountered in the management of these rare tumors. Our findings highlight
the need for better diagnostic precision, especially in the context of hybrid treatment
approaches, and reinforce the importance of collaborative efforts to build robust
tumor registries and evidence-based treatment strategies for this underrepresented
subset of childhood renal tumor. To the best of our knowledge, ours is only the second
study from India after Qureshi et al, to exclusively document the outcomes of NWRTs.[5] By categorizing patients into three therapeutic groups, we aimed to extract clinically
meaningful insights from this heterogeneous disease entity. Despite the limitation
of retrospective design and limited sample size, our study adds valuable regional
data to the limited global literature on NWRTs. Even though discrepant cases were
discussed in institutional clinicopathological meetings, the lack of a central/independent
pathology review remains a key limitation in our study focused on histology-driven
therapeutic misclassification.
Conclusion
In conclusion, NWRTs are a heterogeneous group of rare renal tumors among children.
Timely and accurate identification of NWRTs with tailored multidisciplinary management
is essential to improve their outcomes. Developing research avenues through collaborative
efforts across multiple centers holds the key to enhancing our understanding and informing
evidence-based therapeutic strategies for this challenging group of childhood cancers.
