Multidisciplinary Management of Children with Non-Wilms Renal Tumor: A Real-World Evidence from a Tertiary Cancer Care Center in Southern India

Abstract

Introduction

Non-Wilms renal tumors (NWRTs) are a rare group of disorders comprising only 10 to 20% of all pediatric renal tumors. Their timely and accurate identification is critical, as therapeutic approaches differ markedly from those for Wilms tumor. Due to their rarity, the NWRTs remain less well-characterized than Wilms tumor.

Objectives

This study seeks to outline the demographic profile, clinical features, treatment strategies, and survival outcomes of children with NWRTs managed in our center.

Materials and Methods

We conducted a retrospective study on children diagnosed and treated as NWRTs between January 2000 and December 2023 at the pediatric oncology unit of a tertiary care cancer center in Southern India. We categorized the NWRTs into three therapeutic groups: group I: benign tumors requiring surgery only; group II: malignant tumors requiring surgery only; and group III: malignant tumors requiring surgery and chemotherapy—more intensive than the Wilms tumor regimen, with or without radiotherapy

Results

During the study period, 17 children (19% of all renal tumors) were diagnosed with NWRTs in our unit. The distribution of histological variants within our study cohort was as follows: clear cell sarcoma of kidney (n = 6; 35%); renal cell carcinoma (n = 4; 24%), primitive neuroectodermal tumor (n = 2; 12%), non-rhabdomyomatous soft tissue sarcoma (n = 2; 12%), mesoblastic nephroma (n = 2; 12%), and multicystic nephroma (n = 1; 5%). Eleven patients underwent upfront nephrectomy, while six children received preoperative chemotherapy followed by delayed nephrectomy. Pretherapy biopsy was performed in only six patients in our study cohort. The study participants had a median follow-up duration of 97.5 months (range: 25–136 months). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire study cohort were 59% (95% confidence interval [CI]: 32–78%) and 62% (95% CI: 34–81%), respectively. 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 participants 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.

Conclusion

NWRTs represent a rare and diverse group of renal tumors among children. Early and precise diagnosis of NWRTs, coupled with individualized, multidisciplinary treatment strategies, is vital to achieving better outcomes.

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.

Conflict of Interest

None declared.

Data Availability Statement

The data that support the findings of this study are available with the corresponding author.

Authors' Contributions

V.R. conceived the concept, overlooked entire study process, and validated the data and manuscript. P.S. collected the data, did the formal analysis, and prepared the draft of the manuscript. A.R. verified the data and corrected the manuscript. G.D., B.T.K., and G.V.V. corrected the manuscript. The manuscript has been read and approved by all authors. Each author confirms that the manuscript represents honest and original work.

Patients' Consent

Informed consent was waived off by the Institutional Ethics Committee as this study is a retrospective study using anonymized data.

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Publication History

Article published online:
07 November 2025