Pretreatment for Bilateral Nephroblastomatosis is an Independent Risk Factor for Progressive Disease in Patients with Stage V Nephroblastoma

Abstract

Background: Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma.

Methods: Retrospective analysis of 121 consecutive patients with stage V nephroblastoma registered from January 1989 to May 2005. Registration, prospective data collection and treatment were carried out within the framework of 3 consecutive SIOP/GPOH-nephroblastoma-trials.

Results: 19 patients had metastasis and 29 syndromes at diagnosis. 13 patients had been pretreated for bilateral nephroblastomatosis. 1 patient was not treated and 17 patients had upfront surgery. Preoperative treatment duration ranged from 1–12 weeks (n=103). 1–3 preoperative treatment-cycles resulted in average tumor-volume-reduction of 45%. 1 patient underwent bilateral nephrectomy. 52% of the patients had 2 functioning kidneys after the end of treatment. 20 patients had died after mean follow-up of 8.6 years. 5y-Progression-Free (PFS) and Overall-Survival (OS) were excellent for patients having a localized disease without pretreatment for nephroblastomatosis (5yPFS/OS: 80±4%/93±3%). Metastasis at diagnosis (51±12%/56±12%; p=0.003) and pretreatment for nephroblastomatosis (37±14%/67±13%; p<0.001) were associated with significantly poorer outcome. Cox-regression analysis revealed an independent influence of pretreatment for nephroblastomatosis, metastasis and syndromes on PFS. The latter 2 as well as anaplasia and age (<2 years or >3 years) had an independent influence on OS.

Conclusions: Pretreatment for nephroblastomatosis, metastasis and syndromes are independent risk factors. 1–3 preoperative treatment-cycles are sufficient to achieve save nephron-sparing-surgery in most patients.

Zusammenfassung

Hintergrund: Die Behandlung von Patienten mit einem Stadium V Nephroblastom ist komplexer und variabler als bei Patienten mit unilateralem Nephroblastom.

Methoden: Retrospektive Analyse von 121 Patienten mit einem Stadium V Nephroblastom, die von Januar 1989 bis Mai 2005 im Rahmen dreier aufeinander folgenden SIOP/GPOH Studien registriert und behandelt wurden.

Resultate: 19 Patienten hatten Metastasen, 29 Patienten ein komplexes Syndrom bei Diagnose. 13 Patienten waren bereits wegen einer Nephroblastomatose behandelt worden. 17 Patienten wurden primär operiert. 1 Patient erhielt keine Behandlung. Die präoperative Behandlung von 103 Patienten dauerte 1–12 Wochen, entsprechend 1–3 präoperativen Zyklen. Es wurde eine Volumenreduktion von Ø 45% erzielt. 52% der Patienten hatte nach Operation 2 funktionierende Nieren, nur ein Patient erhielt eine bilaterale Nephrektomie. Nach einer Nachbeobachtungszeit von Ø 8,6 Jahren waren 20 Patienten verstorben. Patienten mit einer lokalisierten Erkrankung ohne Vorbehandlung haben ein 5y-PFS und OS von 80±4% respektive 93±3%. Metastasen bei Diagnose (51±12%/56±12%; p=0,003) und Vorbehandlung für eine Nephro­blastomatose (37±14%/67±13%; p<0,001) gingen mit einem signifikant schlechterem Überleben einher. In der COX-Regressions-Analyse zeigten Vorbehandlung, Metastasen und Syndrome einen unabhängigen, signifikanten Einfluss auf das PFS. Die beiden Letzteren sowie Anaplasie und Alter (<2 Jahre oder >3 Jahre) hatten einen unabhängigen Einfluss auf das OS.

Schlussfolgerung: Vorbehandlung für Nephroblastomatose, Metastasen und Syndrome sind unabhängige Risikofaktoren. 1–3 präoperative Zyklen reichen in der Regel aus, um eine sichere, nierenerhaltende Operation zu ermöglichen.

Key words

nephroblastoma - bilateral - stage V - SIOP - metastasis - stage IV

Schlüsselwörter

Nephroblastom - Bilateral - Stadium V - SIOP - Metastase - Stadium IV

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