Second malignant neoplasms in patients treated on SIOP Wilms tumour studies and trials 1, 2, 5, and 6

The incidence of second malignant neoplasms (SMNs) was investigated among 1,988 patients with complete data, enrolled in the SIOP Wilms tumor trials and studies 1, 2, 5, and 6, treated between September 1971 and October 1987. By the end of 1992, eight SMNs were documented, whereas only 1.3 were expected (standardized incidence ratio [SIR] = 4.15; 95% CI = 1.79, 8.17). The risk increases in the first 10 years from diagnosis, while no apparent excess of risk is observed in the subsequent periods. This finding however is difficult to interpret due to the low statistical power. The cumulative incidence of a second cancer observed at 15 years after Wilms tumor diagnosis was 0.65%. Six SMNs were registered in the cohort of patients treated in the SIOP studies 1,2 and 5 (999 cases) compared to the two cases observed in the SIOP6 cohort (989 cases). If the suggested reduced incidence of second cancers between SIOP1-5 and SIOP6 patient cohorts is confirmed by longer follow-up, it might reflect changes in the treatment protocols. Med. Pediatr. Oncol. 29:239–244, 1997. © 1997 Wiley-Liss, Inc.     

Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood

The previous International Society of Paediatric Oncology (SIOP) trials and studies recognized three prognostic groups of renal tumors of childhood: low risk, intermediate risk, and high risk tumors, which were further defined in the SIOP (Stockholm) Working Classification of Renal Tumors of Childhood (1994). The results of the latest SIOP Trials and Studies showed that certain histological features which remain after preoperative chemotherapy, such as blastema, are of prognostic significance while others are not. Therefore, in the next SIOP Trials and Study a revised classification of renal tumors will be followed. It still recognizes the three tumor risk groups with different types in each of them, but for treatment purposes, only three major types of nephroblastoma need to be recognized: completely necrotic (low risk tumor), blastemal (high risk tumor), and others (intermediate risk tumors). Patients will be treated according to tumor histology and stage. Trials which include preoperative chemotherapy have shown that the presence of necrotic tumor or chemotherapy induced changes in the renal sinus or perirenal fat can be ignored for distinguishing between stage I and II, but if present at resection margins or lymph nodes, it should be regarded as stage III. Prognostic significance of all histological component of Wilms tumors will be studied prospectively in the new trial.     

A single-institution Wilms' tumor and localized neuroblastoma series

Since January 1980, 120 children affected by Wilms' tumor have been treated at Bambino Gesù, mostly with multimodality treatment according to Société Internationale d'Oncologie Pediatrique (SIOP) protocols, including chemotherapy, surgery and radiotherapy in selected cases. This treatment approach emphasizes the role of preoperative (neoadjuvant) chemotherapy as opposed to the approach favored by the National Wilms' Tumor Study, which is focused on optimizing postoperative chemotherapy after primary surgery. Thus, using SIOP guidelines, staging occurs at the time of surgery, after chemotherapy administration. These differences will constitute the baseline for a comparison between the two experiences. Bilaterality, nephroblastomatosis, partial nephrectomy in unilateral Wilms' tumor and thrombosis of the vena cava are the main topics discussed. For the present study, the analysis was restricted to 98 consecutive cases diagnosed until December 1999, for whom at least 24 mo of follow-up is available. The more recent experience of treating resectable neuroblastoma in cooperative studies dates back to 1979, when the first Italian Cooperative Group Neuroblastoma protocol was introduced. This experience was continued within the frame of the first Localized Neuroblastoma European Study Group protocol (LNESG 94), and will be compared to North American Cooperative Group approaches and outcomes. Preoperative evaluation of surgical risk factors, intraoperative complications and their management, and long-term outcome will be discussed.     

Laparoscopic treatment of renal cancer in children: A multicentric study and review of oncologic and surgical complications

ObjectiveThe aim was to report a multicentric study with a longer follow-up to evaluate the laparoscopic radical nephrectomy in children with renal cancer.Material and methodsThis was a retrospective multicentric study, from October 2005 to January 2012, of children who underwent a laparoscopic radical nephrectomy for small renal malignant tumors.ResultsSeventeen children were included in this study. Sixteen underwent chemotherapy before surgery according the SIOP (Société Internationale d'Oncologie Pédiatrique) protocol and one was treated by surgery only for a carcinoma. All except one could be treated by laparoscopy; the biggest tumoral size was 8 cm. The median hospital stay was 3 days (2–10). The pathologic examination showed 15 Wilms' tumors, one clear cell sarcoma and one TFE3 renal cell carcinoma. With a median follow-up of 42 months (range 12 and 77 months) after laparoscopic radical nephrectomy, 15 children had no oncological complications (port site or local recurrence, pulmonary metastasis) and one had a local recurrence without intraoperative tumoral rupture. The child with TFE3 renal cell carcinoma died 4 years after surgery from brain and lung metastases without local recurrence. No small bowel obstruction occurred.ConclusionsRadical nephrectomy in children for Wilms' tumor or other renal cancer can be safely performed laparoscopically and our indications can be summarized, for trained laparoscopic surgeons, by small tumors under about 8 cm diameter, especially without crossing the lateral edge of the vertebra on the CT scan at the time of surgery.     

Surgery of cavoatrial tumor thrombus in nephroblastoma: a report of the SIOP/GPOH study

BACKGROUND: Resection of a Wilms tumor extending through the inferior vena cava into the right atrium represents a challenge to the pediatric surgeon. Exact preoperative diagnosis is essential to identify the tumor and its intravascular extension. To achieve a complete excision of the tumor cardiopulmonary bypass and hypothermia may be required. The feasibility of a complete resection is important as it guides subsequent therapy such as chemotherapy and radiation. PROCEDURE: In order to define these issues, we reviewed the records of 33 of 1,151. Patients enrolled in the SIOP 93-01/GPOH Study and the SIOP 2001/GPOH Study who had a tumor thrombus into the inferior vena cava and into the right atrium. RESULTS: The median age at diagnosis was 3.73 years. Twenty-four patients had a tumor thrombus into the inferior vena cava, in nine patients the thrombus reached into the right atrium. All patients were operated on; cardiopulmonary bypass was used in nine patients. There were no deaths intraoperatively. Twenty-nine children are still alive; four patients died, one patient due to aspiration and failed resuscitation, two patients died from a recurrent tumor, and one child due to an unresectable primary tumor. CONCLUSION: Our report suggests that Wilms tumor extending to the inferior vena cava and the right atrium is technical challenging, but with adequate preoperative diagnosis and a multidisciplinary surgical approach including cardiopulmonary bypass and hypothermia, the prognosis is favorable.     

Topography of childhood tumors: pediatric coding system

The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.     

Treatment Refusal and Abandonment in Children with Acute Lymphoblastic Leukemia

The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.     

Radiotherapy in the SIOP (international society of pediatric oncology) nephroblastoma studies: A review

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either pre-operatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined. © 1994 Wiley-Liss, Inc.     

Multimodal therapy for children and adolescents with Ewing Sarcoma: Results of the First National Chilean Trial (1986–1991)

Thirty-seven patients with Ewing sarcoma were treated in the First National Chilean Trial for Ewing's Sarcoma (1986–1991), which comprised the St. Jude Ewing's 78 Study. All patients received cyclophosphamide, doxorubicin, vincristine, and Dactinomycin for a total treatment period of about 10 months, and all prescribed therapy was administered. Local therapy consisted of irradiation (RT) to the primary tumor, complete surgical resection, or a combination of both surgery and RT. Twenty-nine of these patients had localized tumors, 24% had pelvic primary tumors, 21 were males, and 20 were greater than 10 years of age at diagnosis. Twenty-one patients had tumors that were greater than 8 cm in largest diameter. Fourteen of the 29 patients with localized disease remain disease free at 23 to 91 months from diagnosis. Fourteen patients have died oftumor-related complications and 1 of a secondary malignancy. Relapse was local only in 4, metastatic in 9, and local plus metastatic in 1. Only 1 of the 8 patients with metastatic disease at presentation remains disease free. Toxicity consisted primarily of myelosuppression and mucositis. We conclude that this form of relative intense multimodal therapy for children/adolescents with localized Ewing sarcoma is curative in about half of affected children as in the original St. Jude study, and that it can be safely given in a developing country, provided that careful attention to supportive care and treatment planning is given. Although these results represent improvement in outcome for our patients, more effective therapy is needed for children with Ewing sarcoma, especially those with metastatic disease at presentation. Med. Pediatr. Oncol. 29:190–196, 1997. © 1997 Wiley-Liss, Inc.     

National Wilms Tumor Study: An Update for Pathologists

The National Wilms Tumor Study (NWTS)-5, begun in August 1995, incorporates some important new definitions and concepts that have critical importance in determining therapy and prognosis. The criteria for stage 1 were refined to accommodate an important subset of stage 1 Wilms tumors that are being managed by nephrectomy alone, without the use of adjuvant therapy. The distinction between stages 1 and 2 in the renal sinus is no longer defined by the hilar plane but by the presence or absence of venous or lymphatic invasion. Specific problems encountered in the interpretation of the renal sinus are discussed here. The topographical definition of focal anaplasia has proven to be of prognostic value and is incorporated into the NWTS-5 study design. Received August 19, 1997; accepted August 20, 1997     

New definitions of focal and diffuse anaplasia in Wilms tumor: the International Society of Paediatric Oncology (SIOP) experience

BACKGROUND: Unlike the original definitions of focal (FA) and diffuse anaplasia (DA) in Wilms tumor (WT), recently redefined FA and DA proved to be of prognostic significance. The aim of the study was to analyze WT from the SIOP file, the majority of which were treated with preoperative chemotherapy, in order to investigate whether chemotherapy influenced the presence of anaplasia, whether the new definitions were applicable to these tumors, and whether they were of prognostic significance. PROCEDURE: The unilateral anaplastic WT of children up to 16 years of age from the SIOP 6 and 9 nephroblastoma trials and studies were first classified according to the original definitions and analyzed. Then they were reclassified and analyzed according to the new definitions. RESULTS: Anaplasia was diagnosed in 86 (5.5%) of 1,554 unilateral WT. The age at diagnosis ranged from 9 to 175 months (median, 63) and more than half of children were over 5 years of age. From 15% to 85% of the tumor mass showed chemotherapy-induced changes. Blastemal anaplasia was seen in 74, stromal in 23, and epithelial in 22 cases. According to the original definitions, FA was diagnosed in 55 (64%) and DA in 31 (36%) cases. In total, 48% children were alive and well, including 53% with FA and 39% with DA (P = 0.23). When reclassified, 39 old FA cases were moved to the new DA group, resulting in 70 (81%) DA and 16 (19%) FA cases. The female-to-male ratio for FA changed from 1.9:1 to 1:1 while remained unchanged for DA. The percentage of FA stage I cases increased from 31% to 44%, while it decreased from 25% to 6% for stage III. For other stages it remained virtually unchanged. The overall 4-year actual survival was 75% for FA and 41% for DA (P = 0.03). CONCLUSIONS: Preoperative chemotherapy did not obliterate or produce anaplasia. The new definitions were applicable to pretreated cases and they were of prognostic significance.     

Survival of patients with metastases from Wilms' tumor (SIOP 1, SIOP 2, SIOP 5)

Data of patients with metastases from Wilms' tumor, either at diagnosis or after first treatment, were collected from 25 European centers. Eligible for survival analysis were 293 patients, 142 from SIOP 1, 46 from SIOP 2 and 105 from SIOP 5. There were 134 boys and 159 girls aged between 2 and 216 months with a median of 54 months. The follow-up time for surviving patients was betweeen 6 months and 142 months with a median of 75 months. At the end of the study, 119 patients are alive disease-free and 174 have died, 19 in complications (2 without tumor); one patient died in acute lymphoblastic leukemia. SIOP 2 patients did significantly worse than those from the SIOP 1 and 5 groups. The following variables were significant for the outcome: (a) site, (b) histology, (c) treatment. A possible reason for the low survival in the SIOP 2 patients is discussed.     

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: A review

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, respresent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Inter-group Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas. © 1993 Wiley-Liss, Inc.     

Treatment of Wilms tumor according to SIOP 9 protocol in Casablanca, Morocco

BACKGROUND: Childhood Wilms tumor represents one of the challenge for pediatric oncologists in developing countries. We report the characteristics and treatment results of patients with Wilms tumor according to SIOP 9 protocol in Morocco. PROCEDURE: From January 1989 to December 2000, 86 children with Wilms tumor were admitted. The diagnosis was based on physical exam and abdominal ultrasound. The metastatic work-up was based on abdominal ultrasound and chest X-ray. RESULTS: The mean age was 36 months (3-120 months). The sex-ratio was 1. Abdominal mass was the main symptom at presentation (84 cases). There were 13 metastatic cases. Treatment applied was according to SIOP 9 Protocol without randomization. Local deases was present in 75 patients with stage I in 38 cases (50%), IIN0 in 4 cases (6%), IIN1 in 9 cases, and III in 24 cases (44%). The distribution of pathologic groups was: favorable in 4 cases, standard in 69 cases, and unfavorable anaplastic type in 2 cases. Sixty-nine patients were evaluable for therapeutic evaluation. Other patients were lost to follow-up. Three patients died of treatment related toxicity and 13 patients relapsed. With a median follow-up of 70 months, the 5-year EFS and 5 years overall survival for evaluable patients are 77.4% and 79%, respectively while the 5-year EFS for all patients was 56%. CONCLUSION: These results are encouraging for a developing country but special efforts should be done to reduce the rate of abandonment.     

Complete necrosis induced by preoperative chemotherapy in Wilms tumor as an indicator of low risk: report of the international society of paediatric oncology (SIOP) nephroblastoma trial and study 9

BACKGROUND: The SIOP Nephroblastoma therapeutic protocols include a period of preoperative chemotherapy followed by nephrectomy and a period of postoperative chemotherapy. From the outset, identification of low-risk groups has been an aim of the SIOP Nephroblastoma Trials and Studies. Now that 90% of children with Wilms tumor can be cured, attention is even more focused on the identification of patients who could benefit from less aggressive postoperative therapy, thus minimizing the morbidity and late effects associated with treatment. The prognostic implications of total necrosis in nephroblastoma after chemotherapy have not been investigated hitherto. PROCEDURE: Between November 1, 1987 and June 30, 1993, 599 patients referred to the SIOP-9 Nephroblastoma Trial and Study were preoperatively treated and classified as stages I-IV nonanaplastic Wilms tumor. RESULTS: Of these 599 patients, pathologic examination of the nephrectomy specimen revealed a completely necrotic Wilms tumor (CNWT) with no viable tumor remaining in 59 (10%): these comprised 37 stages I-III and 22 stage IV. Of these patients, 58 (98%) had no evidence of disease at 5 years vs. 90% for the rest of the cohort (P < 0.05). Stages I-III patients represented 63% of CNWT and had a 97% overall survival rate. The only death was related to veno-occlusive disease and occurred in a stage I patient in the month following nephrectomy. Stage IV patients represented 37% of CNWT (vs. only 10% of all other cases of unilateral nonanaplastic Wilms tumor) and had a 100% rate of survival. Children with CNWT were older (mean 59 months vs. 43 months); their tumor at diagnosis was larger and had regressed more significantly at subsequent ultrasound examination. The data also uphold the hypothesis that Wilms tumors of blastemic pattern are most aggressive, but also are extremely responsive to chemotherapy. CONCLUSIONS: Patients with unilateral nonanaplastic WT that showed total necrosis following preoperative chemotherapy had excellent outcome and should benefit from less aggressive postoperative treatment in further trials. Other very responsive tumors, such as Wilms with <10% viable tumor, should also be assessed.     

The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP,COG, SIOP‐E,SIOP‐PODC,IPSO, PROS,CCI, and St Jude Global

The COVID‐19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS‐CoV‐2 (COVID‐19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low‐ and middle‐income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP‐PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.     

A 23-year experience with malignant renal tumors in infancy and childhood.

A retrospective analysis of 77 children treated between 1974 and 1996 was undertaken to evaluate morbidity and the evolution of therapy. A Wilms' tumor (WT) was present in 73 children. 74% of patients (pats.) with WT survived (54 of 73 pats.). Histological specimens of 67 patients were re-evaluated, including 4 children with non-WT histology. Among patients with Wilms' tumors (WT), nephroblastoma (NB) of intermediate risk predominated (73%; 46 of 63 pats.). Low-risk tumors occurred in 5 of 63 children (8%; mesoblastic nephroma 3, cystic partially diff. NB 1, completely necrotic NB 1). High-risk WT were diagnosed in 12 of 63 patients (19%) (NB with anaplasia 10, clear cell sarcoma 1, malignant rhabdoid tumor 1). Nephrogenic rests were present in 14 cases. We observed 3 children of school age with renal carcinoma and one patient with an intrarenal neuroblastoma. WT histology was the most important factor determining prognosis (p = 0.018). The risk for relapses was 2.6-fold higher in patients with high-risk WT compared to the standard risk group. Stages were re-evaluated according to SIOP 93-01. Comparing relapse-free survival of stages I, II and III, respectively, there was a reduced survival rate for stage III (p=0.019). According to the SIOP/GPOH protocol in 1989, the regimen was switched from primary surgery to preoperative chemotherapy without biopsy in 1989 (11 pats.). Compared to earlier years, survival improved (n.s.). In 3 patients preoperative diagnosis by means of imaging failed. During preoperative chemotherapy a venous occlusive disease of the liver occurred in 2 patients. Preoperative chemotherapy led to an impressive tumor shrinkage in the majority of patients. 2 patients of the preoperative group died (focal anaplastic NB). Long-term morbidity was analysed in 49 patients and included radiation-induced scoliosis (35), chest-wall deformity (3), congestive cardiomyopathy after relapse (1) and arterial hypertension (2). Over the years there was a trend to reduce frequency and dose of irradiation. Prognosis of WT is excellent but unfavorable histology (high risk) predicts a poor prognosis. In our experience, reduction of tumor volume due to preoperative chemotherapy facilitates tumor removal by surgery and may prevent tumor spillage and the deleterious effects of radiation in young children. Surgery without delay is necessary if the diagnosis is unclear or the tumor fails to respond to preoperative chemotherapy.     

PLUTO first report

The PLUTO is a registry developed by an international collaboration of the Liver Tumors Strategy Group (SIOPEL) of the SIOP. Although the number of patients collected in PLUTO to date is too small to add any analytic power to the existing literature, this new registry has great promise. It has been created to clarify issues regarding the role of liver transplantation in the treatment of children with unresectable liver tumors. By reviewing the results to date, we hope we can motivate more centers to participate, enroll patients, complete data entry, and boost the potential impact of the collaborative effort. To achieve this goal, a large number of patients are needed, which requires an intensified international collaboration. Pediatric oncologists, pediatric surgical oncologists, and pediatric liver transplant surgeons are all encouraged to participate and contribute. This is a preliminary glimpse of what we hope to be a series of interim reports over the next decade from the steering committee to help guide therapy in this very challenging group of children.     

Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor

BACKGROUND: The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. PATIENTS AND METHODS: In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. RESULTS: 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. CONCLUSION: Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.