Update on Relapses in Unilateral Nephroblastoma Registered in 3 Consecutive SIOP/GPOH Studies – A Report from the GPOH-Nephroblastoma Study Group

Abstract

Introduction: Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced.

Patients and methods: We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially.

Results: 3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11).

Conclusion: Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group.

Zusammenfassung

Einleitung: Die Behandlung und Stratifikation von Progressen/Rezidiven (PD) unilateraler Nephroblastome hat sich in den letzten 20 Jahren weiterentwickelt. Risikofaktoren sowie neue Chemotherapeutika wurden in die Therapiepläne integriert.

Methoden: Wir berichten über die Ergebnisse der Behandlung aller 251 Patienten mit einem Progress oder Rezidiv eines unilateralen Nephroblastoms im Vergleich der 3 Studien SIOP9/GPO (n=77), SIOP93-01/GPOH (n=93) und SIOP2001/GPOH (n=81).

Resultate: Das 3-Jahres-Gesamtüberleben (OS) aller Patienten nahm von 43% auf 61% und 59% zu (p<0,01). Das 3y-OS für lokalisierte Stadien (I–III) nahm von 43% auf 65% und 68% zu, während es für Stadium-IV-Patienten nur geringfügig von 43% auf 53% und 44% zunahm. Als unabhängige Risikofaktoren konnten in der Multivariatanalyse die kürzere Zeit bis zur PD, lokales Stadium III, kombinierte PD und Hochrisikohistologie bestätigt werden. 26 Patienten, die eine Hochdosistherapie erhalten hatten, erreichten eine 3y-OS von 64%, verglichen zu 54% für die restlichen Patienten (p=0,11).

Fazit: Die Strukturierung der Behandlung sowie neue Medikamente haben zu einer deutlichen Verbesserung der Prognose geführt. Patienten der Sehr-hohes-Risiko-Gruppe benötigen neue Therapiestrategien und Medikamente, die nur durch eine internationale Zusammenarbeit validiert werden können.

Key words

unilateral Wilms’ tumor - stem cell transplantation - recurrence - nephroblastoma in adults - high risk relapse - nephroblastoma

Schlüsselwörter

unilateraler Wilms-Tumor - Stammzelltransplantation - Rezidiv - Nephroblastom bei Erwachsenen - Hochrisikorezidiv - Nephroblastom

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