Long‐term outcome of bilateral Wilms tumors (BWT)

Abstract

INTRODUCTIONApproximately 5-7% of Wilms tumor (WT) patients present with bilateral disease [1]. Modern WT management consist of ample chemotherapy, nephron-sparing surgery, and, when indicated, radiotherapy. The focus of treatment is survival, and especially in this group of patients the preservation of good longterm renal function is of utmost importance. Nevertheless, the surviving individual may develop renal failure or late effects due to anticancer treatment. The aim of both European and American study groups has been to use preoperative chemotherapy to allow tumor shrinkage and increase the chance for NSS. With the changing methodology in the treatment over time, the overall renal failure has decreased from 16.4% in NWTS 1-2, and 9.9% in NWTS-3 to 3.9% in NWTS-4, although with varying follow-up periods [2]. The incidence of end-stage renal failure (ESRF) was 0.6% for unilateral tumors, 11.5% for bilateral tumors, and >50% for Denys-Drash syndrome (DDS)/WAGR syndrome [1]. Within the group including bilateral tumors, metachronous tumors have a higher incidence of ESRF as compared to synchronous tumors (18 vs. 9%) [2]. Causes were bilateral nephrectomy for persistent or recurrent tumor (74%), DDS, radiation nephritis, chemotherapy toxicity, and surgical complications. Of these, DDS and radiation nephritis were the most significant causes [2].The aim of this study was to analyze the long-term outcome (follow-up >5 years) of patients treated at our center with respect to survival, renal function, and late effects (secondary tumors). PATIENTS AND METHODSBetween 1967 and 2007, 344 patients were treated for WT at the Emma Children's Hospital AMC. Of this cohort, 41 (11.9%) patients (23 females) with a median age of 2.25 years (range 4 months-8 yrs), were diagnosed with Bilateral WT (BWT). Twenty-eight (8%) were synchronous and 13 (3.8%) were metachronous. Seven presented with distant metastasis at diagnosis, five with lung metastasis, one with liver metastasis, and one with both lung and liver. Almost all were treated according to International Society of Pediatric Oncology (SIOP) protocol recommendations, with a combination of chemotherapy, surgery, and radiotherapy if indicated. However, the first SIOP study started in 1971, and in the first protocols no recommendations were given and patients were treated according to center decisions.Data were retrospectively collected from the patient records, operative reports, office notes, and long-term follow-up clinic notes. Four patients had to be excluded for lack of data, because they lived in another country, or because our center was only involved in the diagnostic process or saw the child for a second opinion, after which they returned to their own regional hospital for further treatment and follow-up. Ten patients died of disease, nine within 5 years after diagnosis. Long-term follow-up was defined as a follow-up >5 years by which 25/28 children could be included in the analysis (Fig. 1). The following data were collected: age at diagnosis, gender, tumor type (met...

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…500+ ml AV-2. 500+ ml 35 observed that functional renal outcome was considerably better after bilateral nephron sparing surgery (NSS) than when other types of surgery were used 35 . Independently of the type of treatment, children with Wilms tumour, aniridia, genitourinary anomalies, and retardation (WAGR), Denys-Drash or other syndromes associated with WT1 mutations, are at increased risk of ESRD 36 .…”

“…Independently of the type of treatment, children with Wilms tumour, aniridia, genitourinary anomalies, and retardation (WAGR), Denys-Drash or other syndromes associated with WT1 mutations, are at increased risk of ESRD 36 . Thus, avoiding total nephrectomy at initial surgery is advised for bilateral tumours in the UMBRELLA protocol 35 . However, other important causes of ESRD exist, including tumour recurrence requiring bilateral nephrectomy or renal irradiation.…”

Nephron-sparing partial nephrectomy for bilateral Wilms' tumor

“…Although PN has never been studied in a prospective, randomized trial and is more technically demanding than a nephrectomy, the risk involved is generally considered to be acceptable to avoid the deleterious sequelae of bilateral total nephrectomy. Likewise, the previous recommendation that children with Wilms' tumor undergo unilateral nephrectomy, neoadjuvant chemotherapy, and delayed PN makes little sense in light of more recent data that suggest that preserving parenchyma in each kidney is not only often feasible but also associated with better long-term renal function and avoidance of dialysis [12]. Several reports have been published describing experiences with NSS for BWT.…”

Experience with Retroperitoneal Partial Nephrectomy in Bilateral Wilms Tumor

“…[1][2][3] The challenge in treating bilateral Wilms tumor (BWT) is achieving a cure while preserving renal function, because these patients are at an increased risk of end-stage renal disease, even in the absence of associated renal anomalies. 1 Recent studies in BWT have shown that preoperative chemotherapy followed by resection preserves more renal parenchyma, 1,4 and this management strategy is now the standard of care.…”