Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study

Murphy AJ, Brzezinski J, Renfro LA, Tornwall B, Malek MM, Benedetti DJ, Cost NG, Smith EA, Aldrink J, Romao RLP, Dome JS, Davidoff AM, Treece AL, Parsons LN, Mullen EA, Shamberger RC, Paulino AC, Lo AC, Geller JI, Ehrlich PF. Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study. Int J Cancer. 2024 Nov 15;155(10):1824-1831. doi: 10.1002/ijc.35080. Epub 2024 Jul 8. PubMed PMID: 38973574; PubMed Central PMCID: PMC11570340.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled on Children’s Oncology Group (COG) AREN0534, a multicenter phase III clinical trial conducted from 2009–2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that timing of events could be visualized, both overall and within pre-specified groups. 222 children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported of which 48 were relapse/progression. The overall 8-year EFS was 75% (95%CI: 69%−83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over two years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and FHWT patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.