Adherence to Protocol Recommendations for Children With Wilms Tumour in Two Consecutive Studies in the United Kingdom and Ireland-Does Variation Matter?

BACKGROUND AND AIMS: Wilms tumour (WT) has excellent event-free and overall survival (OS). However, small differences exist between countries participating in the same international study. This led us to examine variation in adherence to protocol recommendations as a potential contributing factor.

METHODS

Retrospective analysis of risk-stratified chemotherapy and radiotherapy regimens given to children with unilateral WT treated with pre-operative chemotherapy in the SIOPWT2001 (2002-2011) and Improving Population Outcomes for Renal Tumours of Childhood (IMPORT) (2012-2018) studies in the United Kingdom and Ireland. Pre- and post-operative treatments were classified as per protocol (PP), deviation (PDEV)-variation for specified clinical reasons, violation (PVIOL)-not treated PP.

RESULTS

A total of 1256 children with WT were registered by 20 centres. A total of 1052 (84%) had unilateral WT treated with pre-operative chemotherapy. All had centrally reviewed pathology. Case report forms allowing categorisation of the whole treatment pathway were available for 756 (72%) patients. Treatment was classified as PP in 452 (60%), PDEV in 175 (23%) and PVIOL in 129 (17%). Stage III/IV tumours had higher proportion PVIOL (21% and 35%, respectively) compared to Stage I/II tumours (8%-10%). Two-thirds of patients were treated in 'high-volume' centres (≥5 new WTs/year). Protocol adherence rates were similar between high- and low-volume centres. Protocol adherence category had no impact on event-free or OS.

CONCLUSIONS

Protocol guidelines are followed closely for lower stage tumours, but there is greater variation in advanced disease. Centre size showed no association with survival, emphasising the effectiveness of using a national treatment protocol, supported by central pathology review.