The Relationship Between the Site of Metastases and Outcome in Children With Stage IV Wilms Tumor

Abstract

Summary:The aim of this study was to analyze in detail the site of metastasis of stage 4 Wilms tumor (WT) and its correlation with outcome. The databases from 3 major European pediatric cancer institutions were screened for children with WT between 1994 and 2011. Of 208 children identified, 31 (14.9%) had metastases at diagnosis. The lung was affected in 29 children (93.5%) and the liver in 6 children (19.4%). Twenty-seven children (87.1%) had metastases isolated to 1 organ, with the lung being the most common site (80.7%). Five-year overall survival was significantly better in those children with distant disease in either lung or liver (95.8%) compared with those affected in both lung and liver (57.1%, P = 0.028). Further, prognostic markers were the response of metastases to preoperative chemotherapy (P = 0.0138), high-risk histology (P = 0.024), and local stage (P = 0.026). Five-year overall survival was 82.1% and 5-year event-free survival was 67.9%. The overall follow-up time was 74.1 and 87.2 (2 to 151) months among survivors, and the treatment-related complication rate was 16.7%. In conclusion, in our series of stage 4 WT, prognosis was excellent if histology was favorable, metastatic disease was isolated to either lungs or liver, and if metastases responded to preoperative chemotherapy.Key Words: metastases, pediatric cancer, risk stratification, survival, Wilms tumor (J Pediatr Hematol Oncol 2013;35:518-524) W ilms tumor (WT) is the most common renal malignancy in childhood and the second most frequent intraabdominal pediatric cancer after neuroblastoma. 1 Many recent advances in clinical care and the biology of this tumor have pushed the overall survival (OS) to 90%. Naturally, for children with distant metastases the OS is lower. 1 Little is known on metastatic disease in stage 4 WT and its implication on therapy and outcome. 2,3 The lungs have long been recognized as a common site of distant tumor spread in stage 4 WT and several recent studies focus on this entity. 1,2 To our knowledge, no complete description of the metastatic profile of stage 4 WT at diagnosis exists at present. Therefore, in this study we reviewed children treated at 3 European pediatric cancer institutions for WT regarding their metastatic profile at diagnosis and its implication on long-term outcome. METHODS AND PATIENTS PatientsA retrospective analysis of the WT databases at the following 3 institutions was carried out: Hannover Medical School, Hannover (Germany); Dr. von Hauner Children's Hospital, Munich (Germany); and Virgen del Rocı´o Children's Hospital, Seville (Spain). Inclusion criteria were metastatic disease at diagnosis. Consequently, children with lower stage tumors who relapsed with metastatic disease were excluded. Additional exclusion criteria were other renal tumor entities like clear cell sarcoma, rhabdoid tumor, or renal cell carcinoma. TreatmentStaging criteria for WT was based on an upfront chemotherapy-based system developed by the International Society of Pediatric Oncology (SIOP). Treatment was accord...

Considerations in the Diagnosis and Management of Pediatric Patients With Favorable Histology Wilms Tumor Who Present With Only Pulmonary Nodules

“…[12] Smets et al reported that lung biopsies obtained after treatment with preoperative chemotherapy were positive for tumor (or necrotic tumor) in 85% (17/20) of patients. [21] Some in both of these series were also reported by Berger et al [22] The finding that outcome is better for patients with CT-only lung nodules than for those with nodules detectable by plain chest radiograph [19,21,23] supports several interpretations, including that some patients with CT-only nodules have only benign nodules and the volume of disease is less among those with CT-only nodules compared to nodules identified on plain chest radiograph.…”

Management and outcome of pediatric metastatic Wilms’ tumor at the National Cancer Institute, Egypt

“…Reports from other developing African countries indicate a higher incidence of stage IV WT among their cohorts, with a reported incidence of 30.9%, 40%, and 42% in Nigeria, Kenya, and South Africa, respectively [8,9]. While in developed countries, the incidence is relatively lower, with a reported incidence of 12%, 14.9%, and 17% in Children Oncology Group (COG), German study, and International Society of Pediatric Oncology (SIOP), respectively [10,11]. This high incidence of advanced stages of WT noticed in developing countries could be attributed to several factors such as lack of awareness among caregivers and healthcare professionals regarding early presentations of WT, limited resources and poor access to health care that lead to late presentations, and advanced disease stage at diagnosis.…”

A comprehensive review of nephroblastoma with ureteric involvement

“…Even in advanced tumor stages, complete excision of the urinary tract tumor and optimal treatment of disseminated malignancy are pivotal to overall patient management and outcome. Increased global reporting of ureteric involvement by nephroblastoma is necessary to determine the exact significance of the different involvement patterns, especially when metastatic disease is well controlled with current and emerging therapeutic modalities [28]. More detailed prospective studies, including phenotypic, immunophenotypic and genotypic appraisal of the ureteric component of nephroblastomas that have not been exposed to neoadjuvant chemotherapy may be helpful in determining potential associations between ureteric involvement and the biological profile of the primary renal and contiguous ureteric tumoral components.…”

“…Furthermore, the aim of current nephroblastoma management schedules, within and beyond the confines of the kidney and ureter, is to control disease and improve patient quality of life. Chemotherapy, radiation and metastatectomy may be employed to ensure such management objectives [28], but the latter is relatively new practice in our center; metastatic disease in the study patients was managed by chemoradiation exclusively.…”