The variable clinical spectrum of nephroblastomatosis – results from the German Society of Pediatric Oncology and Hematology (GPOH) childhood kidney tumor group.

Abstract Background: Histologically nephroblastomatosis consists of ≥2 microscopic foci of nephrogenic rests. In contrast, clinically apparent nephroblastomatosis consists of single, multiple or diffuse hyperplastic nephrogenic rests (HNR) that can be mistaken for nephroblastoma on imaging. Their treatment and outcome are as variable as published results.Methods: Analysis of 78 patients having clinically apparent uni- or bilateral nephroblastomatosis out of 2347 patients registered for a renal tumor in the consecutive International Society of Pediatric Oncology (SIOP)93-01/GPOH and SIOP2001/GPOH studies between 1993 and 2014. Results: Median age at diagnosis and follow-up was 13 months (0–12.7 years) and 9.2 years, respectively. 59% of patients were female, 57% had bilateral and 53% multifocal or diffuse nephroblastomatosis. Radiologic diagnosis was conclusive in 67% when reviewed centrally versus 30% without review (p=0.015). 27% of patients developed nephroblastoma(s). On histology 45% were high-risk, 30% intermediate-risk and 25% upfront-surgery-blastemal subtype. 5-year-event-free (EFS), nephroblastoma-free-(NFS) and overall-survival (OS) were 60.7%, 79.8% and 95.5%, respectively. Univariate risk factors for EFS/NFS were female gender (p<0.001/p=0.031), bilateral (p=0.002/p=0.03) and diffuse HNR at diagnosis (p<0.001/p=0.016), and non-complete remission (non-CR) at the end of first-line-treatment (both p<0.001). Gender and non-CR remained significant in multivariate COX regression analysis for EFS (p=0.005 and <0.001, respectively), non-CR also for NFS (p=0.002). 34 of 74 evaluable patients achieved CR within 12 weeks after diagnosis, 25 of them had no further treatment and were followed, 9 received chemotherapy. Their EFS was 78% and 100%, respectively.Conclusion: Nephroblastomatosis confronts clinicians with a variety of pitfalls, but overall survival is excellent. However, patients need an extended follow-up for more than a decade. In patients who have achieved CR within 12 weeks, a relatively short treatment is sufficient. Contrary, the risk of progression for patients having bilateral and diffuse HNR is significantly increased, despite prolonged treatment. A clear common terminology is needed for future trials to facilitate true comparability of results.