A 10-Year Study of the Outcome of Wilms' Tumor in Central India and Identifying Practice Gaps.

Introduction: Despite remarkable improvement in Wilms' tumor (WT) survival in Western world, sub-optimal outcome in resource-constrained settings is influenced by late presentation, larger size, and poor access to treatment. This prompted us to study the outcome at a tertiary care center and to identify the global and local practice gaps. Materials and
Methods: A retrospective, observational study of WT was conducted from October 2009 to September 2019 at a tertiary care setting. Following the National Wilms' Tumor Study Group protocol, an upfront nephrectomy (unilateral resectable tumors) and preoperative chemotherapy (large/unresectable Stage I-III) were followed. The records were reviewed for demographics, stage, preoperative chemotherapy, predictive factors, and outcome. Survival curves were plotted by the Kaplan-Meier method, and analysis was performed using the SPSS software version 16.
Results: One hundred and fifty-six children were included, median age was 4.1 years, with a male predominance. The most common stages of the presentation were II (40.4%) and III (34.6%). An upfront surgery was done in 27.6%, while remaining received preoperative chemotherapy. The median follow-up was 22 months, and the events included relapse in 46 (29.48%) and death in 54 (34.61%). The mean survival time was 45.7 (95% confidence interval [CI], 41.08-50.30). The 2-year overall survival was 65.38% (95% CI, 59-73), and the 2-year event-free survival was 36% (95% CI, 32-41). On comparison of the impact of preoperative chemotherapy, the survival estimates in Stages I-III and relapse rate were statistically similar, tumor size reduced significantly, and tumor spill was significantly lower (P < 0.05).
Conclusion: WT is associated with late presentation, sub-optimal survival, and higher relapse in our setting associated with practice gaps related to the management including practice violations. Copyright:

INTRODUCTION

Wilms' tumor (WT) is the most common primary renal malignancy in children. It is one of the most common childhood cancers where persistently innovating multimodal strategies have led to the conversion of almost uniformly fatal disease to one with excellent survival. With optimized use of current treatment strategies, including chemotherapy, surgery, and radiotherapy (RT), the 5-year overall survival (OS) of 90% can be achieved.[12] Surprisingly, despite such remarkable improvement in survival in the developed countries, the outcome of WT in resource-challenged settings continue to be sub-optimal.[34] OS ranged from 70% to 97% in high-income countries, 61%–94% in upper-middle income countries, 0%–85% in lower-middle income countries, and 25%–53% in low-income countries.[5] This prompted us to retrospectively analyze our 10-year data at a tertiary care center in Central India and identify the “global” and “local” practice gaps which prevent uniformity in treatment protocols and hinder the achievement of “textbook outcomes.”

MATERIALS AND METHODS

This retrospective observational study of WT in children was conducted at a tertiary care center of Central India from October 2009 to September 2019. The Pediatric Surgery unit's electronic records of these children were reviewed for age at diagnosis, sex, stage, preoperative chemotherapy, type of surgery, tumor characteristics, postoperative treatment, and outcome. The staging was done according to the National Wilms' Tumor Study Group (NWTSG). A modified NWTS protocol was adopted in this study. Preoperative imaging was also used in addition to surgicopathologic assessment for the purpose of staging.[6] A contrast-enhanced computed tomography (CECT) of the abdomen and pelvis was obtained to define the local extent of the tumor. Imaging of the thorax (CECT or chest radiography) was done only when it was feasible, due to cost constraints. Doppler of inferior vena cava (IVC) was performed in all patients along with CECT to identify IVC involvement. An upfront nephroureterctomy with lymph node sampling (without preoperative chemotherapy) through a transabdominal incision was followed by adjuvant chemotherapy in children with unilateral resectable tumors evident on preoperative imaging. All Stage I–III tumors displacing or crossing aorta or vena cava and unresectable (extrarenal spread, renal vein and IVC involvement, and peritoneal spread) Stage III and IV tumors on imaging were offered preoperative chemotherapy (according to NWTS) followed by a delayed nephrectomy. The decision for resectability of the tumor was based on the preoperative imaging findings. All patients undergoing preoperative chemotherapy underwent a flank tru-cut core needle biopsy. Chemotherapy was administered as per the NWTSG-V protocol and according to the weight (<30 kg)/surface area (>30 kg), as applicable. Postoperative RT to the flank was planned according to the stage and histology of the tumor as per the NWTSG protocol and was given to all patients who got preoperative chemotherapy. In children with diffuse peritoneal implants or intraoperative spillage, whole-abdomen RT was performed. After the completion of therapy, children were followed up in the pediatric surgery outpatient department for the relapse/recurrence and outcome. The follow-up visits were scheduled once a month for the first 6 months, and then every 3 monthly for the next 6 months, and thereafter every 6 months. Children who had a relapse were treated using chemotherapy with a combination of cyclophosphamide, carboplatin, and etoposide. Survival curves were plotted for OS, event-free survival ([EFS], death and relapse were counted as events) and relapse-free survival (RFS) by the Kaplan–Meier method to know the estimates. Statistical analysis was performed using the SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc. and P < 0.05 was considered statistically significant.

RESULTS

During the study period, 156 children with previously untreated unilateral WT were registered at our center were included. The demographic and other characteristics of the included patients are summarized in Table 1. The median age of the affected children was 4.1 years (interquartile range [IQR], 2–5 years) with a male predominance (male:Female ratio of 1.55:1). The most common stage of the presentation was Stage II (40.4%). Stage III disease (34.6%) included extrarenal local invasion (33), positive abdominal lymph nodes by histology (8), invasion + lymph node involvement (6), and intra-operative tumor spillage.[7] Along with local extension, 2 had tumor thrombus involving the IVC at the diagnosis and 7 had thrombus reaching the renal vein but no extension into the IVC. The extra-renal extension in Stage III tumor (33) was found as an invasion in Gerota's fascia (28), Psoas fascia (4), and diaphragm (1); however, they could be excised completely. While 11 patients had lymph node involvement in Stage III (one of them being preoperatively Stage II disease but finally labeled as Stage III) and three patients had lymph node involvement in Stage IV.

Table 1

Demographics and other characteristics of patients with Wilms' tumor in the present study (n=156)

Criteria	n (%)
Age at diagnosis (IQR)	4 years (2-5 years)
Sex
Male:female	95:61
Side
Right:left	104:52
Presenting complaint
Mass	156 (100)
Fever	143 (91.66)
Hematuria	5 (3.20)
Size at presentation (cm)	10.32±3.1 (6.5-15)
Stage
I	30 (19.23)
II	63 (40.38)
III	54 (34.61)
IV	9 (5.76)
Histopathology (n=156)
Favorable	147 (94.23)
Anaplastic	9 (5.76)
Lymph node sampling (146)	Positive in 14/146 (9.58)
Upfront surgery (n=43)
I	22/30 (73.33)
II	13/63 (20.63)
III	7/54 (12.96)
IV	1/9 (11.11)
Preoperative tru-cut biopsy and chemotherapy (n=113)
I	8/30 (26.66)
II	50/63 (79.36)
III	47/54 (87.03)
IV	8/9 (88.88)
Relapse (n=46)
Overall	46/156 (29.48)
I	4/30 (13.33)
II	15/63 (23.80)
III	26/54 (48.14)
IV	1/9 (11.11)
Mortality (n=54)
Overall	54/156 (34.61)
I	3/30 (10) (relapse-3)
II	14/63 (22.22) (relapse-10, 4-sepsis during chemotherapy)
III	29/54 (53.70) (relapse-22, 7-sepsis during chemotherapy)
IV	8/9 (88.88) (terminal illness-8)

IQR: Interquartile range

An upfront nephrectomy followed by adjuvant chemotherapy was done in 43 patients (27.6%). The remaining 113 patients received preoperative chemotherapy and later underwent a delayed nephroureterectomy. The median duration of preoperative chemotherapy was 7 ± 2.6 weeks. After preoperative chemotherapy, the tumor size (longest dimension) regressed significantly (after chemotherapy - 4.7 ± 1.3 cm vs. before chemotherapy - 10.32 ± 3.1 cm, respectively, P < 0.0001). Of the 43 children who underwent upfront nephrectomy, 7 (16.3%) had spill and so were labelled as Stage III. None of the patients in the delayed nephrectomy group had tumor spill or rupture (P = 0.02). On exploration, four patients with large Stage II disease on preoperative imaging were found to be unresectable (Stage III disease with adherence to major abdominal vessels) who later on underwent successful oncological surgery after preoperative chemotherapy.

Among children with Stage IV diseases, the site of distant metastasis included lungs in seven cases, the liver in 1 case, and peritoneum in 1 case.

Surgical complications were infrequent and minor; however, three patients developed adhesive intestinal obstruction; one of them required operative treatment and there was no operative mortality.

Planned chemotherapy was tried to be administered according to schedules, with an effort to minimize delays. However, 34 (21.8%) patients did not complete their adjuvant treatment either because they abandoned the treatment (23) or died during the first few months of chemotherapy.[8] Of 122 patients who completed treatment, 32 patients (3 in Stage I, 12 in Stage II, and 17 in Stage III) did not follow a strict chemotherapy regimen and had a delay of more than 8 weeks in schedule completion. The course of RT was irregular due to long waiting in the RT department and poor compliance by the patients. Only 12 patients (28.6%) completed RT as per schedule, whereas others had delayed patient turn-up (24, 57.1%) or delay due to long RT waitings (14.3%). None of the patient could be started on RT within 14 days of surgery as it was not fesible in our setup.

The median follow-up was 22 months (IQR, 11–60). The KM OS and EFS estimates for all analyzed patients are shown in Figures 1a and b and 2a and b. The mean survival time (95% confidence interval [CI]) was 45.7 (41.1–50.3). The stage-wise mean survival time was 61.7 (95% CI, 54.9, 68.4), 50 (95% CI, 44.6, 55.4), 27.6 (95% CI, 21.2, 34.1), and 10.8 (95% CI, 5.9, 15.7) for Stage I–IV, respectively. The 2-year OS was 65.38% (95% CI, 59–73) and the 2-year EFS was 36% (95% CI, 32–41).

Figure 1

(a and b) The survival estimates of the Wilms' tumor for the whole group

Figure 2

(a and b) The survival estimates stratified according to stages of Wilms' tumor

Relapse was observed in 46 of 156 patients (29.5%), and the median time of relapse was 20.5 months (IQR, 12.25–22) from the initial diagnosis. None of the patients had gross local residual disease after definitive surgery in any of the stages while only 1/9 Stage IV had complete remission. Eight children had a relapse limited to the local site, 27 had relapsed at local and distant sites, and 11 children had relapse only at a distant site. The distant sites of relapse included lungs (21), liver (14), bones (2), and brain (1). All local relapse were >5 cm, mean size of 8.8 ± 3 cm. All relapses in Stage IV were distant to the lungs. The overall 2-year estimate is shown in Figure 3a and b. The high relapse rate was further studied and was found that 17 (36.95%) and 24 (52.17%) had poor compliance with chemotherapy and RT, respectively. Out of 46 relapses, 38 died under treatment and 8 survived (I-1, II-3, III-3, and IV-1).

Figure 3

(a and b) The 2 year relapse-free survival estimates for Wilms' tumor in the present study

However, on comparison of the impact of preoperative chemotherapy with the Log Rank (Mantel-Cox) test, the variation in survival estimates in Stages I, II, and III was statistically insignificant (P = 0.889, 0.883, and 0.843, respectively). The local relapse for Stage I, II, and III diseases on the comparison between delayed nephrectomy (underwent tru-cut biopsy) and upfront nephrectomy (no biopsy) was statistically insignificant (P = 0.639, P = 1, and P = 1, respectively). However, none of the patients in the delayed nephrectomy group had tumor spill as compared to the upfront nephrectomy group (6/43), P = 0.02.

The mortality during the treatment course was due to advanced disease (43) and sepsis occurring during chemotherapy.[8]

DISCUSSION

Focused research and better knowledge in WT have improved the outcome in developed countries; however, despite available knowledge expected improvements are not seen in developing countries. This prompted us to retrospectively analyze our 10-year data at a tertiary care center in Central India. We could identify many local practice gaps that are unique to resource-constrained settings and also some global practice gaps which prevent uniformity in the treatment protocols and achievement of “textbook outcomes” globally.

The sub-optimal outcome in India is mainly due to late presentation, the larger size of the tumor, poor access to specialized treatment, and lack of clarity in treatment protocols that are specific to these settings.[57] This is compounded by under-reporting due to a lack of cancer registries. Published Indian studies are scarce and reports a combined total of only 319 cases, reported survival was 54%–85%, and the relapse rate was 13%–20% [Table 2].[89101112] All these studies uniformly show a late presentation of WT with a significant number of patients in higher stages [Table 2]. A close scrutiny of these publications reveals wide variations in the staging and management protocol selection. All authors adopted an individualized protocol, suggesting a clear need for developing a resource-poor setting-specific protocol. Table 3 shows a detailed analysis of practice gaps in the present study.

Table 2

A review of Indian studies on Wilm’s tumor

Study	Data collected	n	Median age	Male/female	Size	Staging	Regimen adopted	Biopsy
Sen et al., 1998[9]	1985-1995	71	6 week-15 years	40/31	Stage I-II large and adherent	Preoperative + surgicopathologicalI - 38.02%, II - 15.49%, III - 16.90%, IV - 19.71%, V - 8.45%	Individualized	15 FNAC/trucut (3 massive, 1 after exploratory laparotomy, 11-others)
Trehan et al., 2012[10]	1999-2003	20	19.9 months	6/14	Not mentioned	Surgicopathological stagingI - 20%, II - 65%, III - 15%, IV - 0	Modified SIOP	FNAC (18), error rate of 16% (2 diagnosed neuroblastoma and 1 germ cell tumor)
Guruprasad et al., 2013[11]	2003-2010	61	3.3 years	56/44	Large, not measured	SurgicopathologicalI - 27.8%, II - 16.4%, III - 37.7%, IV - 14.8%, V - 3.3%	NWTS IV protocol	None
Verma and Kumar 2016[8]	2005-2014	108	2.5 years	4/1	Large, not measured	Preoperative + surgicopathologicalI - 21%, II - 30%, III - 35%, IV - 10%	NWTS IV protocol	59/108 received NACT without biopsy
John et al., 2018[12]	2004-2014	59	36 months	59/41	523 cc	PreoperativeI - 38%, II - 16%, III - 9%, IV - 27%, V - 10%	SIOP WT 2001	All
Present study	2009-2019	122	4 years	74/48	Mean size on presentation10.26±3.3 cm	Preoperative + surgicopathologicalI - 28 (22.95%)II - 52 (42.62%)III - 36 (29.50%)IV - 6 (4.91%)V - Excluded	Modified NWTS IV protocol	82/122 underwent trucut biopsy and preoperative chemotherapy

RT: Radiotherapy, NWTS: National Wilm’s tumor study, OS: Overall survival, EFS: Event-free survival, WT: Wilm’s tumor, FNAC: Fine-needle aspiration cytology, DFS: Disease-free survival, IVC: Inferior vena cava, NACT: Neoadjuvant chemotherapy, SIOP: Société internationale d'oncologie pédiatrique

Table 3

The practice-gap analysis and its possible impact on the practice guidelines at global and low- and middle-income countries levels

Focus area	Current state (based on rapid review)	Practice gaps on the basis of existing knowledge and findings of the present study	Possible impact	Realm of impact
Timing of presentation	Late stages and size	Lack of awareness among parents, practitioners, and pediatricians is lacking[58-12] Only 19.23% were Stage I disease Large size at presentation (10.32±3.1 cm) Upfront surgery possible in 27.56% cases	Early detection and awareness campaign by society “1-min awareness video update for parents, pediatricians, general practitioners, general surgeons”	LMICs
Preoperative staging	Preoperative local staging which is an important criterion to allow decision-making is not well-defined for late presentation[13-16]	Factors affecting preoperative staging such as large size, contralateral spatial extension, the indentation of major vessels are not included in the assessment[571718] If preoperative chemotherapy is followed, then it categorizes tumor as Stage III to begin with, irrespective of imaging findings. Combination of preoperative staging and surgicopathologic staging during delayed surgery (whichever was higher) was used for patients undergoing preoperative chemotherapyAmong 113 patients receiving preoperative chemotherapy, 8/30 (26.66%) and 50/63 (79.36%) were characterized as Stage I and Stage II, respectively, which is not according to NWTS protocol, which recommend categorizing them as Stage III and treated accordingly. This may also be responsible for the high relapse rates of 14.28% in Stage I and 28.84% in Stage IIPertinent to mention here that CECT chest was done only when feasible due to cost constraints is another possible practice gap in the current setting	More comprehensive preoperative staging	Global
NWTS versus SIOP protocol	Both COG (erstwhile NWTS) and SIOP protocols are practiced in India[619]	Both protocols have their certain advantages; however, either of the followers lends up in protocol violations due to switching between either[620] Modified NWTS protocol adapted to suit local needs in the present study- The deviations from NWTSG protocols as have been done in this study which was a major practice violation	A revised protocol is desired utilizing the best of the two protocols which is best suited for LMICs	LMICs
Surgical exploration	According to NWTS protocol surgical exploration is advisable for staging	Large tumors and locally advanced disease is common in LMICs, predisposing to undue exploration and higher tumor spill[17,18]16.66% of patients were found inoperable on surgical exploration due large tumor displacing and stretching major vesselsThe tumor spill was more in the upfront surgery group as compared to delayed surgery group (P<0.05)	Preoperative staging with a consideration for spatial extension will avoid undue exploration	LMICs
Preoperative needle biopsy	Preoperative chemotherapy is started with (FNAC/Trucut) or without a biopsy. The needle biopsy is known to “upstage” the tumor according to the COG protocol[21]	Identification of histology and establishing a diagnosis of WT is essential, as after chemotherapy histology gets altered. Moreover, in India, oncologists refrain from starting chemotherapy without a histological diagnosis. However, needle biopsy is not a criterion to upstage the tumor according to recent studies[21,22]The relapse rate for Stage I and II was similar between upfront surgery group and delayed surgery (with biopsy) groups (Stage I - 15% vs. 12.5%, Stage II - 30% vs. 27.5%, respectively), P>0.05	Preoperative tru-cut biopsy (posterior) in all patients who undergo preoperative chemotherapy is advisable	Global
Preoperative chemotherapy	Current indications SIOP- All NWTS- Unresectable on exploration, Stage III, IVC thrombus, Bilateral	Upfront surgery with lymph node sampling is the “gold standard.” However, because of large tumors (Stage I and II) in resource-constrained setup; therefore, preoperative chemotherapy is widely used in our country to improve resectability and reduce tumor spill[1923-29] The tumor spill was more in upfront surgery group as compared to delayed surgery group (P<0.05), suggesting the consideration for preoperative chemotherapy for late presentation over exploration	Revised indications of Preoperative chemotherapy are desired which is best suited for the problems unique to resource-constrained settings utilizing the best of the two protocols	LMICs
Radiotherapy	At present, patients with NWTS Stage III and Stage IV tumors are offered radiotherapy	In the present study, the Stage I and II tumors undergoing preoperative chemotherapy (which was supposed to be categorized as Stage III) with an intent to improve resectability did not undergo radiotherapyRT within schedule according to NWTS is within 14 days of surgery. This was not feasible in our settings and is a major practice gapNWTS protocol mandates flank RT for all patients who receive preoperative chemotherapy as all these should be staged as Stage III irrespective of the LN status on delayed surgery, was a practice violation in the present study	Large tumors at presentation need individualized guidelines with respect to RT as well
Stage redistribution	For patients undergoing preoperative chemotherapy, all patients are staged as Stage III to begin with[620]	Staging before and after preoperative chemotherapy does not correlate. Labeling all patients undergoing preoperative chemotherapy as Stage III (as recommended by NWTS) is likely to overstage the tumor. This may result in a discrepancy of stage-wise survival[1718] This is a concern when large Stage I and II tumors are included for preoperative chemotherapyPreoperative staging may avoid undue exploration for staging and patients can straight-away go for chemotherapy on the basis of imaging	Final staging should be either preoperative or surgico-pathologic, whichever is higher, for patients undergoing preoperative chemotherapy. This can avoid overstaging and understaging	Global
Relapse	Large local relapse is common	The prognosis of large relapse is dismal which adversely affect the overall outcome of WT. Management guidelines for large relapse are not clear[30] The median time of relapse was 20.5 months (IQR, 12.25-22) from the initial diagnosis All local relapses were >5 cm, mean size of 8.8±3 cm The overall 2 years relapse-free survival estimate was 62.19%, which is quite low Only 8/46 patients of relapse were treated completely and were cured, while others died during treatment	Due mention is needed for management of large relapses in the practice guidelinesEarly recognition of relapse need to be advocated with proactive follow-up	LMICs
Follow-up and compliance	Dropouts in follow-up after surgery or the treatment completion is common	The need for stricter follow-up regimen, e-callouts, and patient education is not focused uniformly[530] Overall poor compliance to CT and RT was noted	Customized patient information, education, and communication tools need to be developedElectronic records	LMICs
Survival	Overall and Event-free survival for all stages are inferior to western or “textbook outcome[5]”	Late presentation, large tumor size, late stages compounded with practice gaps in resource-constrained settings predispose to practice violations, which adversely affect the results in terms of OS, EFS and relapse-free survival estimates[5,20]Only 43 (27.56%) have survived for more than 4 years and 34/156 (21.79%) patients did not complete treatment and either died (11) in the early phase of postoperative chemotherapy or abandoned adjuvant treatment (23)	Overall addressal of practice gaps would be a welcome step to improve survival	LMICs

RT: Radiotherapy, NWTS: National Wilm’s tumor study, OS: Overall survival, EFS: Event-free survival, WT: Wilm’s tumor, FNAC: Fine-needle aspiration cytology, IVC: Inferior vena cava, NACT: Neoadjuvant chemotherapy, CECT: Contrast-enhanced computed tomography, COG: Children’s oncology group, LMIC: Low- and middle-income countries, LN: Lymph node, CT: Computed tomography, SIOP: Société internationale d'oncologie pédiatrique

Our overall mean survival time was 45.7 (95% CI, 41.08, 50.30). The stage-wise mean survival time was 61.67 (95% CI, 54.914, 68.443), 50 (95% CI, 44.595, 55.419), 27.6 (95% CI, 21.202, 34.084), and 10.8% (95% CI, 5.852, 15.703) for Stage I–IV, respectively. These may appear sub-optimal when compared to those from developed countries and few of the Indian studies; however, these are similar to the results found in other resource-constrained settings.[125] The higher age (median age of presentation 4 years), large tumor size (mean size of the tumor 10.32 + 3.1 cms), late stages on presentation (only 19.23% presented in Stage I, most of Stage II and III tumors had crossed the midline; therefore, requiring preoperative chemotherapy, upfront surgery was feasible in only 27.56% of patients), higher relapse rate (poor compliance with chemotherapy and RT schedules in only 31.14% and 28.57%, respectively), and late presentation of relapse (due to irregular follow-ups relapses were quite large by the time they were noticed and often associated with distant metastases) are the major reasons for our inferior outcomes. The major local practice gaps identified in our setting are shown in Table 3. The OS and EFS RFS were found to be sub-optimal in this study, which are largely related to resource-challenged factors, practice violations, early abandonment of treatment, or poor compliance to adjuvant treatment.

Apart from the findings of the present study, a further practice-gap analysis showed the current state of practice gaps and their possible impact on the practice guidelines at the local and global level, as shown in Table 3. These predominantly include the dichotomy in staging and treatment guidelines of Société internationale d'oncologie pédiatrique (SIOP) and Children's Oncology Group (COG) classification systems (upfront surgery vs. preoperative chemotherapy); the controversy regarding preoperative/prechemotherapy Tru-cut needle biopsy; how to tackle the low sensitivity in the detection of capsular penetration (elevating Stage I to II) by computed tomography/magnetic resonance imaging scans; importance and inclusion of weight and size of the tumor and tumor histology (anaplasia) in prognosis; quandary of stage reduction after preoperative chemotherapy; and earlier diagnosis of asymptomatic relapses by more frequent follow-ups and surveillance scans.[13141516171819202122303132333435363738] Already winds of change are blowing with some convergence of ideology between the guidelines of SIOP and COG systems with an attempt at the identification and selection of patients who will benefit from preoperative chemotherapy.[2339] The overall and stage-wise survival remains similar regardless of adopting either of the two philosophies.[2437] Similarly, Indian authors have incorporated the weight and size of the tumor and tumor histology (anaplasia) in the planning treatment protocol.[25] However, expectations of preoperative chemotherapy in large WTs resulting in decreased tumor spillage rate or improved survival are not always met.[8122627] As a result, most of the centers in India adopt individualized policy between upfront surgery and preoperative chemotherapy in large size tumors, late stages, and hope for minimizing the risk of rupture.[2528] In the present study, high rate of relapse, large size relapse, and higher relapse-related mortality are another area which needs special attention and were because of late stage disease, certain protocol violations/practice gaps [Table 3], late presentation of relapse not amenable to treatment, and poor treatment compliance. Another striking finding in the study was high median time of relapse (20.5 months) which is usually less than an year in WT. The explanation for this finding may be late presentation of relapse which are noticed as large-sized relapse, all local relapses being >5 cm (mean size of 8.8 ± 3 cm).

Lack of sharply defined data from low- and middle-income countries (LMICs) is a global problem; as worldwide collated data from the International Agency for Research on Cancer contains only 8%–21% data of cancer patients from the developing world.[29] Better and systemic reporting of data, creation of more cancer registries, and improved participation in the existing National Cancer Registry Program will go a long way to mitigate this deficiency.[40]

Our 10-year retrospective analysis of WTs including practice-gap analysis leads to many questions – answers to these will help in achieving uniformity in the treatment protocols and step forward to achieve “textbook outcomes” in LMICs. Society of Pediatric Urology, under the aegis of the Indian Association of Pediatric Surgeons, has already distinguished itself in the leadership role and formulated standard treatment guidelines for WTs.[41] A revision of the WT guideline, addressing these knowledge-practice gaps will be of immense help for all the pediatric surgeons working in LMICs, similar to other societies who have modified the guidelines according to the geographical variations.[1718]

CONCLUSION

WT is associated with late presentation, large size, sub-optimal survival, higher relapse, and poor compliance to postoperative treatment in our setting. This study identifies the “global” and “local” practice gaps related to late presentation, preoperative staging/biopsy, the dichotomy of existing protocols, preoperative chemotherapy, stage redistribution, and sub-optimal survival. There is a need for the revised guidelines which address and bridge the practice gaps, which are unique to resource-constrained settings to improve the outcomes of WT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.