A 21-year study on nephroblastoma by the University of the Free State revealed unique challenges, with the scientists noting that future research should analyse confounding factors to gain a more comprehensive understanding of the complexities of this common paediatric cancer.
Nephroblastoma (Wilms tumour) is a childhood malignancy primarily affecting the kidneys, accounting for ~5% of all paediatric cancers globally – and being the most common form of renal cancer in children aged <15 years.
Its prevalence in South Africa (10%-13.5%) is concerning, presenting a considerable healthcare challenge that demands immediate attention and thorough investigation.
The clinical manifestation typically includes the insidious development of an asymptomatic abdominal mass, abdominal discomfort, haematuria, hypertension and urinary tract infections.
The disease can affect a single kidney or both kidneys, and because diagnosis relies on meticulous physical examinations, urinalysis and comprehensive imaging studies, asymptomatic patients may not be identified until the disease is advanced.
Early detection and appropriate treatment crucial
The standard of care in SA aligns with a modified International Society of Paediatric Oncology (SIOP) protocol for African countries. It classifies the disease into five distinctive stages based on parameters such as tumour extent, histological characteristics and bilateral involvement, guiding treatment strategies and predicting patient outcomes.
Global survival rates for nephroblastoma exhibit significant disparities with developed nations reporting four-year rates of up to 90%, starkly contrasting with sub-Saharan African figures, ranging from 11% in Sudan to 66% in SA.
Late presentation in developing countries poses a significant challenge, negatively impacting treatment outcomes and overall survival. This retrospective study at the Universitas Academic Hospital Complex (UAHC) in Bloemfontein and Tygerberg Hospital in Stellenbosch underscored the correlation between disease staging and survival rates, reporting 81%, 69%, 58% and 46% for stages I to IV, respectively.
Black children presenting at later stages experienced diminished survival rates, potentially linked to delayed presentation, poor nutritional status and comorbidities such as HIV and tuberculosis.
Timely and appropriate medical care is critical to prevent delayed diagnoses resulting in advanced disease stages, wrote the researchers in the SA Medical Journal, whose investigation among paediatric patients at the UAHC aimed to determine challenges affecting patient outcomes.
The high prevalence of nephroblastoma in SA emphasises the need for targeted research and healthcare efforts, they recommended, as well as early detection mechanisms to improve survival rates and reduce disparities among diverse demographic groups.
Context
The retrospective cross-sectional study encompassed all paediatric oncology patients undergoing treatment for nephroblastoma at the Paediatric Haematology and Oncology Unit at UAHC from January 2000 to December 2020.
Data were sourced from the Paediatric Haematology and Oncology Tumour Registry and individual patient records, and included demographic, diagnostic, treatment and outcome information.
Pilot study
A pilot study was undertaken with the initial 10 patients to assess the data collection feasibility and the data sheet’s adequacy. Subsequently, no modifications were made to the data collection form, and these patients were incorporated into the main study.
Diagnostic aspects
The median (IQR) symptom-to-diagnosis time was 30 (10 – 60) days, ranging from immediate to one year. Notably, 56.0% of patients (n=116/207) experienced symptoms for >2 weeks before presenting at UAHC. In 47.4% (n=55) of these cases, no specific reasons were provided for the delay in diagnosis.
Stage I disease was diagnosed in 80 (38.6%) patients followed by stage IV (n=61; 29.5%). Some patients died before definitive staging or treatment, comprising an unstaged group of 4.3% (n=9, including one with metastasis).
No significant correlation between tumour stage and the duration of symptoms was found (p>0.9). Tumours were primarily unilateral (n=195; 94.2%), with a slight left-sided kidney tumour predominance in 51.3% (n=100/195) of these patients. At diagnosis, the median (IQR) lactate dehydrogenase (LDH) level, indicating tissue injury and tumour burden, was 783 (137 – 494) U/L
Metastatic disease was found at diagnosis in 32.4% (n=67) of patients, with the lungs being the most prevalent site (n=46/67; 66.7%). Negative isotope studies demonstrated skeletal involvement in 143 (69.1%) patients, liver involvement in 128 (61.8%) and clear bone marrow aspirates in 189 (91.3%).
Based on risk stratification, patients were predominantly categorised as being in the intermediate risk category (n=121; 58.5%). Low-risk cases constituted only 1.4% (n=3), while in 5.3% (n=11), risk stratification was not determined.
Tumour histology revealed intermediate risk in 159 (76.8%) patients, high risk in 12 (8.8%) and low risk in eight (3.9%) patients.
Treatment
In 98.1% (n=203) of cases, patients adhered to the modified SIOP protocol for African nations, while 1.9% (n=4/207) did not. Treatment refusal occurred in 3.4% (n=7) of cases, with a median (IQR) time of 20 (16 – 116) days after treatment initiation. Neo-adjuvant chemotherapy was administered to 196 (94.7%) patients, starting a median (IQR) of 4 (2 – 6) days after diagnosis.
Surgery was performed on 180 (87.0%) patients, with a median (IQR) time to surgery of 50 (36 – 62) days.
Twenty-one (10.7%) patients had an unknown response, as they did not proceed to surgery. Of the 37 (17.9%) patients who received radiotherapy, 19 (51.4%) had stage IV disease, 17 (46.0%) stage III and 1 (2.7%) stage II disease.
Outcome
Throughout the study period, 59.4% (n=123) of patients survived, with a median (IQR) survival rate of 27 (9 – 82) months. A significant correlation was observed between survival and duration of symptoms (p=0.007), risk stratification (p<0.001), metastatic disease (p<0.001) and tumour burden (LDH level) (p<0.002), indicating decreasing survival with prolonged symptom duration and advancing disease stages.
Treatment was completed by 63.8% (n=132) of patients , of whom 81.1% (n=107) survived. Survival was significantly higher among patients who completed treatment (81.1%) compared with non-completers (n=25/84; 29.8%; p<0.001). Twenty (9.7%) patients defaulted on their treatment and 26 (12.6%) were lost to follow-up, although no significant subsequent impact on survival was observed
Goal
The aim was to describe the profile of patients treated for nephroblastoma, including their disease presentation, management and outcomes, and furthermore, to compare patients who survived v. died, and SA v. Lesotho patients, and gain insights into the reasons for delayed presentations.
In the study of 207 patients, mainly black and from SA or Lesotho, they found a median age at diagnosis of 38 months, and that Lesotho patients experienced more severe disease and longer diagnostic delays.
Treatment completion was 63.8%, with 81.1% following protocols. Radiotherapy was given to 17.9% of patients with advanced disease.
The overall survival rate was 59.4%, with a median survival of 27 months. Survival was linked to symptom duration, risk, metastasis and tumour burden.
Improved cross-border healthcare collaboration between SA and Lesotho is needed to reduce delays and enhance outcomes, while the study emphasised the need for targeted interventions to address diagnostic delays and improve healthcare accessibility, especially in Lesotho.
Strategies include enhancing health literacy, refining referral processes, minimising misdiagnoses and addressing socioeconomic barriers to reduce treatment default rates.
Additionally, patients at risk of relapse should be fast-tracked to treatment, suggested the researchers. Future studies should explore the reasons behind diagnostic delays, including cultural and regional variations in healthcare-seeking behaviour.
Collaborative initiatives between healthcare providers in SA and Lesotho are essential to address these challenges comprehensively. A collaborative effort has the potential to shape tailored strategies, improve early detection, streamline treatment pathways and ultimately enhance outcomes for children with nephroblastoma.
Noteworthy observations from the study on patient demographics, diagnostic delays, tumour stage distribution and treatment dynamics revealed regional variations, emphasising the need for targeted interventions.
Study details
Paediatric nephroblastoma at a South African tertiary hospital: A 21-year retrospective analysis
E Brits, E Gerber, J B Sempa et al.
Published in SA Medical Journal Volume 114 No 12.
Background
Nephroblastoma (Wilms tumour) is one of the most common solid tumours of all paediatric cancers (prevalence of 5% globally and 13.5% in South Africa (SA)), with suboptimal survival outcomes, impacting children’s lives. Consequently, there is an urgent need for enhanced early detection strategies, addressing survival rate disparities and late-stage presentations to improve outcomes.
Objectives
To assess profiles, disease presentations, management and outcomes of patients with nephroblastoma at Universitas Academic Hospital Complex (UAHC), and to compare patients from SA and Lesotho, including differences between early and late presenters and reasons for delayed presentation.
Methods
This retrospective cross-sectional study included 207 paediatric oncology patients treated for nephroblastoma at the Paediatric Haematology and Oncology Unit at UAHC, Bloemfontein, SA, from January 2000 to December 2020.
Results
The median age of the study population was 38 months, with a marginal male predominance (50.7%). A 1-month delay occurred between symptom onset and diagnosis, commonly attributed to delayed care-seeking, impacting survival rates. Compared with similar SA studies, a higher stage IV disease rate (29.5%) was observed, and encouraging survival rates (59.4%) correlated with favourable preoperative histology and no relapse. In comparison, Lesotho patients experienced longer delays and presented with more severe disease.
Conclusion
This study highlights the need for collaboration between SA and Lesotho healthcare providers to improve outcomes by addressing diagnostic delays, treatment defaults and response variations in resource-limited settings through community health education, improving access to primary care, offering care-provider training, improving diagnostic resources and addressing socioeconomic barriers.
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